David Sinclair Links GLP-1 Drugs to Doubled Eye-Stroke Risks

PowerfulJRE

Harvard geneticist David Sinclair warns that widespread adoption of GLP-1 weight-loss drugs doubles cases of non-arteritic anterior ischemic optic neuropathy, even as his laboratory advances gene therapies aimed at reversing cellular aging and tissue loss.

AI-assisted summary of Joe Rogan Experience #2537 - David Sinclair — original source. Check the original for full context.

Source published: 2026-08-24

Detailed notes

## Background Published on YouTube by PowerfulJRE on August 7, 2026, this episode of the Joe Rogan Experience features longevity scientist Dr. David Sinclair. The video description highlights Sinclair's credentials as a Harvard Medical School genetics professor, author of "Lifespan," and host of the "Lifespan" podcast, while providing links to his books, foundation, and episode sponsors.

## TL;DR Dr. David Sinclair and Joe Rogan explore cutting-edge longevity science, discussing cellular reversal therapies, gene therapy trials for vision loss, and the role of novel compounds like (+)-JRT and PDE5 inhibitors in healthspan extension. They examine actionable lifestyle habits, including fasting, strength training, sleep hygiene, and avoiding alcohol to reduce biological age. The conversation also touches on AI's transformation of medical research, the genetic roots of human risk-taking, and the broad systemic impacts of GLP-1 drugs.

## Atmosphere & style The discussion is intellectually fast-paced, highly collaborative, and energized by mutual curiosity about peak human performance and biological optimization. Rogan grounds the exchange with visceral personal anecdotes, biohacking experiments, and practical skepticism, while Sinclair provides high-level scientific expertise delivered with pragmatic enthusiasm. The atmosphere balances deep technical dives into genetics and pharmacology with candid, accessible conversations on everyday health habits, parenting, and resilience.

## Key takeaways - [47:40](https://www.youtube.com/watch?v=hxid7FofhMw&t=2860s) Sinclair's lab successfully cultivated human hair on specialized immune-compatible mice using human stem cells. - [49:18](https://www.youtube.com/watch?v=hxid7FofhMw&t=2958s) Low-dose PDE5 inhibitors like tadalafil improve vascular blood flow, assist with hair retention, and suppress tumor-shielding myeloid-derived suppressor cells. - [53:20](https://www.youtube.com/watch?v=hxid7FofhMw&t=3200s) Human clinical trials are testing gene therapy eye injections for glaucoma and NAION, a condition whose incidence has doubled alongside GLP-1 drug usage. - [57:26](https://www.youtube.com/watch?v=hxid7FofhMw&t=3446s) Fasting for up to three days triggers chaperone-mediated autophagy (CMA) to accelerate cellular repair and maintenance. - [01:12:55](https://www.youtube.com/watch?v=hxid7FofhMw&t=4375s) The Harvard Study of Adult Development identified a supportive partner as the single strongest predictor of long-term health and lifespan. - [01:21:47](https://www.youtube.com/watch?v=hxid7FofhMw&t=4907s) AI models and automated robotics are dramatically accelerating longevity drug discovery by analyzing vast scientific literature and running rapid experimental candidate testing. - [01:31:38](https://www.youtube.com/watch?v=hxid7FofhMw&t=5498s) Non-hallucinogenic analogs of psychedelics, such as (+)-JRT, show high antidepressant potential and induce neuroplasticity without hallucinogenic effects. - [01:36:00](https://www.youtube.com/watch?v=hxid7FofhMw&t=5760s) The DRD4-7R gene variant is strongly tied to risk-taking and novelty-seeking behaviors and is present in nearly half of populations in the Americas. - [02:00:14](https://www.youtube.com/watch?v=hxid7FofhMw&t=7214s) Gene therapy can reboot dormant, non-functioning nerve endings in aging eyes back to a youthful functional state without reverting them to stem cells. - [02:01:00](https://www.youtube.com/watch?v=hxid7FofhMw&t=7260s) Deep sleep triggers the glymphatic system to flush out metabolic waste and misfolded proteins from the brain. - [02:06:37](https://www.youtube.com/watch?v=hxid7FofhMw&t=7597s) Regular resistance training and mild hormetic environmental stressors (such as hypoxic and heat exposure) trigger cellular repair and help prevent sarcopenia. - [02:12:27](https://www.youtube.com/watch?v=hxid7FofhMw&t=7947s) Preserving cerebral microvascular health through exercise, PDE5 inhibitors, and NAD+ precursors like NMN is essential for preventing vascular dementia.

## Detailed walkthrough Here is a detailed, faithful walkthrough of the provided transcript segment.

### [00:01](https://www.youtube.com/watch?v=hxid7FofhMw&t=1s) Informal Greetings and "Sir David" The show opens with Joe Rogan welcoming back Dr. David Sinclair, a Harvard geneticist and longevity researcher. They immediately fall into a lighthearted exchange regarding titles and honors. Rogan jokes about whether Sinclair ever uses the title "Doctor," which Sinclair says he never does. Sinclair quips that he is technically "Sir David" in Australia, having been granted a version of a knighthood that allows him to put "AO" after his name, standing for Officer of the Order of Australia. He clarifies that it is mostly an honorable title that doesn't actually change his daily life, comparing it to calling someone "Sir" at a gas station.

Sinclair explains the cultural phenomenon of "tall poppy syndrome" in Australia, where displaying an oversized ego gets you brought down to Earth quickly—often physically in the schoolyard. He shares that he enjoys going back home to Australia because nobody treats him as someone famous or special, creating an even playing field. Rogan expresses his affection for the Australian people, describing them as friendly, fun, and grounded, though both agree that the travel distance from the U.S. to Australia is a brutal haul.

- **Title/Honor:** Officer of the Order of Australia (AO). - **Cultural reference:** "Tall poppy syndrome," where high achievers or those with large egos are cut down or humbled by their peers.

---

### [01:40](https://www.youtube.com/watch?v=hxid7FofhMw&t=100s) Clean Living, Superfood Coffee, and the "Prophet of Longevity" Discussing long-distance flights, Rogan mentions how he used to combine whiskey and Ambien to sleep through the travel, but notes he has "gone clean" and rarely drinks alcohol anymore except for special celebrations. Sinclair agrees that drinking during a podcast would be a bad look for him, gesturing instead to the superfood coffee Rogan provided. Rogan details the mix: a blend of Black Rifle Coffee and Laird Superfood additives created by Laird Hamilton, containing turmeric and coconut milk. Sinclair notes that turmeric is a powerful anti-inflammatory, perfectly aligning with his own scientific work on health and aging.

Jokingly, Sinclair accepts Rogan’s ribbing, allowing himself to be called "Sir David the prophet of longevity." Rogan highlights that this is Sinclair's fourth appearance on the podcast, congratulating him on his ongoing achievements. Sinclair takes a moment to thank Rogan personally, emphasizing that his book *Lifespan* became a massive global bestseller—translated into 40 languages and read millions of times—largely due to the exposure from his first interview on the show. Sinclair notes that writing high-tech science for a general audience was a challenge, but people have become intensely fascinated by personal optimization.

- **Coffee blend:** Black Rifle Coffee mixed with Laird Superfood (featuring turmeric and coconut milk). - **Book impact:** *Lifespan: Why We Age—and Why We Don't Have To* reached millions globally across 40 languages.

---

### [03:34](https://www.youtube.com/watch?v=hxid7FofhMw&t=214s) The Post-2019 Longevity Explosion Sinclair and Rogan reflect on how public perception of health and mortality shifted dramatically around 2019 and 2020. Sinclair notes that when *Lifespan* came out in late 2019, the impending global pandemic forced people under 70 to confront their own mortality for the first time, causing interest in longevity to explode. Rogan observes that optimizing health is now ubiquitous: everywhere he goes, people are discussing protocols like cold plunges, saunas, and red-light therapy. Rogan points out that the primary benefit of these protocols is feeling better in the present moment, which naturally extends lifespan as a byproduct.

Sinclair agrees, emphasizing that living longer doesn't require extreme or overly complicated measures. He asserts that by following basic principles, individuals can easily add 15 years to their lives. Beyond simple daily habits, Rogan steers the conversation toward the cutting edge of formal longevity science, asking about the revolutionary biological treatments that have moved from theory into reality since 2019.

---

### [05:26](https://www.youtube.com/watch?v=hxid7FofhMw&t=326s) Human Age-Reversal Clinical Trials Sinclair discusses how the field of longevity has advanced at a breakneck pace. In 2019, publicly claiming that biological aging could be reversed was viewed as scientific heresy. However, following successful trials in mice and monkeys, the very first human clinical trial for age reversal is actively underway. Sinclair explains that aging has a single root cause present across almost every cell in the body, and that scientists can now safely control and reset that process, effectively reinstalling the body's youthful cellular software.

To illustrate how these therapies are delivered, Sinclair pulls a physical model out of his pocket—a rubber ball with spikes resembling a domesticated, non-pathogenic viral capsid. He explains that these engineered viral vectors carry targeting adapters on their surface. By changing these surface proteins, researchers can direct the delivery vehicle to specific tissues, such as the liver or the eye. Inside the protein capsule sits a specialized DNA payload designed to execute epigenetic reprogramming.

- **Delivery System:** A domesticated viral vector (AAV-style capsid) modified with surface proteins to target specific organs or cell types. - **Trial Application:** Currently being delivered via direct injection into human eyes to treat vision loss caused by glaucoma. - **EPG Drug Name:** Referred to as OSK or ER100 (Epigenetic Reprogramming 100).

---

### [09:05](https://www.youtube.com/watch?v=hxid7FofhMw&t=545s) The First Human Patient and the "Backup Copy" of Youth Rogan jokes that a scientist explaining viral delivery vectors on a talk show sounds like the opening scene of a apocalyptic horror movie where optimized humans end up eating each other 28 days later. Sinclair laughs, acknowledging the sci-fi nature of the work, but stresses that the trial is FDA-approved after rigorous safety testing. Because the treatment is injected directly into the eye—a self-contained organ—there is minimal risk of systemic spread or uncontrolled growth.

Sinclair shares that he witnessed the very first human patient receive the injection earlier in the year. The patient, who was essentially blind in one eye due to glaucoma, bravely volunteered for the procedure. Sinclair reports that the trial is proceeding as planned with zero adverse safety issues so far. He describes a fundamental concept driving his lab's work: the belief that every cell retains a "backup copy of youth." Rather than seeing elderly people as permanently deteriorated, Sinclair views them as biological systems that simply need to be "rebooted" so their cells can read the original genomic software again.

> "Even an old person, I don't see an old person anymore on the street. I just see a person that needs to be rebooted."

---

### [11:53](https://www.youtube.com/watch?v=hxid7FofhMw&t=713s) Yamanaka Factors, OSK, and Reversing Damage Sinclair explains the cellular mechanism behind epigenetic reprogramming by contrasting his approach with the discovery made by Nobel laureate Shinya Yamanaka in 2006. Yamanaka discovered four genes (Oct4, Sox2, Klf4, and c-Myc) capable of resetting adult skin cells all the way back to embryonic-like stem cells. However, turning a living person’s cells into stem cells would cause mass organ failure or cancer. To solve this, Sinclair’s lab omitted the dangerous fourth gene (c-Myc) and used only three genes: Oct4, Sox2, and Klf4, collectively known as **OSK**.

Using OSK resets cellular age back roughly 75% to 80% toward youth without wiping out the cell's identity. Sinclair uses the analogy of an old vinyl record or CD: aging is like scratches on the surface that make the music skip, while OSK acts as a polish that removes the scratches so the cell can read its original information again. In young adults in their 20s, cell identity and performance are at peak performance; as people age, cells lose their identity and forget how to function. By restoring this identity, OSK enables damaged optic nerves to regenerate and function like young tissue.

- **Yamanaka Factors:** Oct4, Sox2, Klf4, and c-Myc (OSK+M). - **Reprogramming Cocktail (OSK):** Leaves out c-Myc (M) to safely reverse cellular age by ~80% without converting mature cells into unspecialized stem cells or causing tumors.

---

### [13:44](https://www.youtube.com/watch?v=hxid7FofhMw&t=824s) Treating Injury, Glaucoma, and Joint Restoration Sinclair notes that while he initially wanted to target the liver, his student Yuancheng Lu convinced him in 2017 that starting with the eye was a safer proof-of-concept. With glaucoma affecting roughly 40 million people in the U.S. alone—and macular degeneration affecting even more—the human health impact is massive. Rogan asks whether this "backup copy" mechanism could also be used to repair physical trauma or joint damage. Sinclair reveals that his lab had already published a cover story in *Nature* (2020) demonstrating optic nerve regeneration after severe injury.

Furthermore, Sinclair highlights recent independent work from a research group in China that took his team's OSK technology and delivered it into mice with damaged, arthritic joints, resulting in full regeneration of muscle and bone tissue back to normal. Sinclair notes that his lab is actively pursuing treatments for back injuries, joint damage, and osteoarthritis. Rogan expresses excitement, noting that while current treatments like stem cell therapy offer minor symptomatic relief, they fail to truly rebuild destroyed cartilage or fully restore joints damaged by sports or martial arts injuries.

[16:05](https://www.youtube.com/watch?v=hxid7FofhMw&t=965s) The Future of Joint Regeneration, Super Soldiers, and Bio-Regulatory Obstacles

Joe Rogan and Dr. David Sinclair examine the horizon of joint reconstruction and cellular rejuvenation, contemplating its downstream effects on elite athletics. Rogan marvels at a future where athletes could perform supernatural physical feats—like dunking from halfway across a basketball court like Michael Jordan—if age-reversing genetic tools become widespread. Sinclair reveals that his lab at Harvard Medical School is already nearly eight years ahead of public awareness, actively developing both a pill and a liquid drink designed to trigger systemic rejuvenation.

When Rogan playfully suggests bypassing FDA regulations to distribute these untested treatments immediately to willing 80-year-olds who have nothing to lose, Sinclair admits that public demand is already overwhelming. He has had to remove his public contact information because desperate individuals—including one fan who refused to leave his building until they met face-to-face—frequently seek early access. The conversation turns to national security when Sinclair discloses that the U.S. government used regulatory authorities to block a $160 million foreign investment into one of his biotechnology companies out of concern over creating "super soldiers" or leaking dual-use genetic tech abroad.

- **OSK Gene Testing:** Future athletic commissions may need to screen competitors via DNA tests to detect illicit insertions of OSK (*OCT4*, *SOX2*, *KLF4*) reprogramming factors. - **Foreign Investment Blocking:** The U.S. government blocked a $160M foreign investment in Sinclair's biotech firm, citing defense and security concerns over performance-enhancing rejuvenation technologies.

---

[19:10](https://www.youtube.com/watch?v=hxid7FofhMw&t=1150s) Soviet Hybridization Programs, Ethics, and Human Engineering

The discussion transitions into historical and modern efforts to engineer enhanced humans or animal-human hybrids. Rogan recounts historical accounts of Soviet attempts during World War II to create chimpanzee-human hybrids as tireless, pain-resistant combatants to replace massive troop losses. The duo review a 2002 paper by historian of science Kirill Rossiianov detailing biologist Ilya Ivanov's ill-fated 1920s interspecies breeding experiments under Joseph Stalin.

Sinclair notes that while cross-species work remains strictly regulated in Western countries, ethical boundaries vary globally. He references modern scientific demonstrations where researchers created hybrid human embryos that were halted before full development. They contrast these lab experiments with commercial genetic selection already available to wealthy parents today in the U.S., who selectively screen embryos via IVF for traits like height, intelligence, and physical appearance—a dynamic reminiscent of the sci-fi movie *Gattaca*.

- **Ilya Ivanov's Experiments:** In the 1920s, Soviet biologist Ilya Ivanov attempted to crossbreed humans and non-human primates to test the boundaries of hybridization. - **Modern Embryonic Selection:** Parents in the U.S. routinely utilize preimplantation genetic testing (PGT) during IVF to select for specific physical and cognitive traits.

---

[23:54](https://www.youtube.com/watch?v=hxid7FofhMw&t=1434s) Autonomous Robotics, AI Companionship, and Social Dynamics

Shifting from biological engineering to technological advancement, Rogan and Sinclair discuss the deployment of humanoid robotics and artificial intelligence. They contemplate a future where autonomous anthropoid robots are deployed to military battlefields or assigned to household chores. Sinclair jokes about the weirdness of telling a domestic robot—which possesses more computational power than all of humanity combined—to go load the dishwasher.

The conversation steers into the social and psychological ramifications of AI companions and sex robots. Rogan argues that while hyper-agreeable AI companions offer effortless validation, real human relationships derive their value from friction, constructive criticism, and personal accountability. An AI that constantly praises a user removes the essential challenges that drive emotional maturity and human growth.

- **AI Interaction Dynamic:** Rogan emphasizes that real-world relationships require discomfort and feedback to foster personal development, whereas AI provides artificial, unconditional validation.

---

[26:13](https://www.youtube.com/watch?v=hxid7FofhMw&t=1573s) Accelerating Drug Discovery: Trillion-Molecule Virtual Screening

Sinclair breaks down how artificial intelligence has transformed molecular biology and drug development in his Harvard laboratory. Tasks that previously required up to 160 years of manual bench work can now be accomplished in just two months. By leveraging high-performance compute clusters alongside structural protein predictions from Google DeepMind's AlphaFold database—which maps over 20,000 human proteins—his team can virtually dock vast libraries of candidate compounds against targeted intracellular enzymes.

Partnering with researchers at St. Jude Children's Research Hospital, Sinclair's lab screened a virtual library of roughly one trillion theoretical and known molecules. They sought a single therapeutic compound capable of executing three to four distinct anti-aging mechanisms simultaneously—a complex task historically beyond traditional pharmacology. Using AI image recognition, his team monitors cultured human skin cells to evaluate whether treatments successfully reset 92-year-old cellular profiles back to a 20- or 25-year-old biological state.

- **Virtual Screening Scale:** Sinclair's lab computationally screened a virtual library of up to 1 trillion candidate molecules down to 200 high-priority leads for direct testing on human cells. - **Lab Scale:** Sinclair operates a specialized core team of approximately 20 students and researchers at Harvard Medical School.

---

[30:33](https://www.youtube.com/watch?v=hxid7FofhMw&t=1833s) Cellular Reprogramming Mechanics: Yamanaka Factors and Epigenetic Clocks

Rogan asks how scientists ensure that cellular rejuvenation halts at an optimal age—around 20 to 25 years old—rather than reverting cells back to an embryonic state or forming tumors. Sinclair explains that the breakthrough came from refining the Nobel Prize-winning Yamanaka factors (*OCT4*, *SOX2*, *KLF4*, and *c-MYC*). His former student, Lu Wang, tested various gene combinations to achieve safe cellular reset.

The key discovery involved entirely omitting the oncogenic *c-MYC* gene, leaving the specific three-factor cocktail known as **OSK** (*OCT4*, *SOX2*, *KLF4*). This precise combination safely resets cellular age without wiping away cellular identity or driving pluripotency into tumor formation. Sinclair notes that while telomere length offers some indication of biological age, measuring DNA methylation patterns—the precise addition and removal of methyl groups ($-\text{CH}_3$) across the genome—provides a far more accurate "epigenetic clock" for tracking reversal.

- **The OSK Factor Cocktail:** Reprogramming uses three of the four Yamanaka factors—*OCT4*, *SOX2*, and *KLF4*—explicitly excluding the cancer-causing *c-MYC* gene. - **Epigenetic Methylation:** Biological age is measured by tracking methyl tags attached directly to DNA, serving as a precise biological clock that can be reversed using genetic or chemical intervention.

[31:41](https://www.youtube.com/watch?v=hxid7FofhMw&t=1901s) Epigenetic Clocks and the "Dark Side" of Rapid Aging

The biological mechanism governing cellular identity hinges on methyl groups. During embryonic development, these chemical tags silence unwanted genes—causing developing neurons to permanently shut off liver or skin genes while keeping nerve-specific genes active. In 2013, Steve Horvath discovered that tracking these methyl patterns functions as a precise biological clock. David Sinclair explains that his lab published research in 2023 demonstrating how DNA damage (such as exposure to solar radiation) degrades these patterns over time, accelerating the aging process. Sinclair notes that scientists now possess the ability to rapidly age mice—a dynamic Joe Rogan jokingly frames as the ultimate assassination or sabotage plot: a state actor spiking someone's drink to make them age decades overnight.

``` DNA METHYLATION & THE EPIGENETIC CLOCK

[ Embryonic Cell ] --( Methyl Tags Applied)--> [ Specialized Neuron ] | | | ( Aging / Solar) v v Unused Genes Silenced Loss of Epigenetic Pattern (e.g., Liver/Skin Genes) --> Epigenetic Clock Ticks ```

The discussion shifts to a speculative cultural future where age is no longer visible on a person's face. Rogan and Sinclair banter about social reactions to massive age gaps in relationships. If a 92-year-old were restored to a 25-year-old physical state, societal taboos around age-gap dating might transform into jealousy over centuries of accumulated wisdom. Rogan jokes that people would start lying about their age in reverse—claiming to be 80 or 90 to flex their longevity—while Sinclair predicts a future where biological testing of epigenetic markers will be the only way to determine a person's true age.

- In 2023, David Sinclair’s lab published research demonstrating that targeted DNA damage can rapidly accelerate biological aging in mice. - Steve Horvath developed the "Horvath Clock," measuring DNA methylation patterns to accurately track biological age across tissues. - Advanced epigenetic tracking allows biological age to be accurately measured using simple skin swabbings or blood samples.

---

[34:10](https://www.youtube.com/watch?v=hxid7FofhMw&t=2050s) Ancient Civilizations, King Lists, and Lost Human Lifespans

Rogan steers the conversation toward alternative archaeology, bringing up ancient Sumerian king lists that record monarchs reigning for thousands of years before a catastrophic global flood. Standard mainstream historical narratives view these timelines as mythological hyperbole. However, Rogan posits an alternative theory: if advanced human civilizations reached engineering peaks in the distant past—evidenced by massive megalithic structures like the Pyramids, Machu Picchu, Sacsayhuamán, and the Trilithon stones in Baalbek—it is plausible they also unlocked genetic engineering and life extension technologies before being reset by a catastrophic comet impact.

> "Imagine if you had 500 years to do research, not just 57 years... The exponential increase in technological innovation that we would have in this society would be absolutely mind-blowing."

Sinclair addresses the theory with academic diplomacy, noting that while he sticks strictly to established scientific evidence as a Harvard professor, history consistently shows that ancient civilizations were far more sophisticated than modern humans give them credit for. The two discuss how radically life would change if living to 100 meant remaining in one's physical prime. Human expectations regarding careers, marriages, and families would expand into multiple distinct lifespans. Sinclair compares our current biological threshold to the early days of aviation, noting that humanity has already built the basic "glider" of longevity, making dramatic life extension an inevitable certainty rather than a speculative dream.

- **Sumerian King List:** Ancient Mesopotamian records detailing pre-flood monarchs who allegedly ruled for multi-thousand-year spans. - **Baalbek Trilithon:** A set of three massive stone blocks in Lebanon, each weighing roughly 800 tons, raised meters off the ground with precision engineering. - **Societal Impact:** Extending healthy human lifespans to hundreds of years would reshape career structures, relationships, and long-term scientific innovation cycles.

---

[39:24](https://www.youtube.com/watch?v=hxid7FofhMw&t=2364s) The 60-Year-Old Illusion and Biological Dysmorphia

The physical trajectory of a 57-year-old today is radically different from that of a 57-year-old in the 1930s. Rogan points out that a century ago, a 60-year-old was functionally considered near the end of life due to heavy smoking, alcohol consumption, lack of basic nutritional knowledge, exposure to pesticides, and minimal emphasis on sleep or resistance training.

``` LIFESTYLE FACTORS OVER TIME

1930s Average 60-Year-Old Modern Optimized 60-Year-Old +-----------------------------------+ +-----------------------------------+ | - Heavy Smoking & Alcohol | | - Resistance Training | | - Nutritional Deficiencies | VS | - Targeted Supplementation | | - Unregulated Toxic Exposure | | - Optimized Sleep & Phototherapy | +-----------------------------------+ +-----------------------------------+ ```

During the episode, producer Jamie pulls up a viral media account featuring Chuando Tan, a Singaporean photographer who gained worldwide fame for appearing 30 despite being nearly 60 years old. Rogan and Sinclair react with equal parts skepticism and amazement, debating whether such extreme youthfulness comes down to incredible genetic luck, plastic surgery, or AI generation. This leads into a broader discussion on body dysmorphia and how the modern cosmetic industry skews public perception of physical age. Sinclair emphasizes that surgical modifications only alter surface appearance, whereas true biological reversal requires restoring cellular youth from within.

- Chuando Tan, a Singaporean photographer, went viral globally for maintaining the physical appearance of a 25-to-30-year-old into his late 50s. - Early 20th-century life expectancy and vitality were severely limited by lifestyle factors like poor sleep, unrefined diets, and heavy environmental toxicity.

---

[41:40](https://www.youtube.com/watch?v=hxid7FofhMw&t=2500s) The Secret Reversal Cocktail, TET Genes, and Erasing Alzheimer's

Sinclair shares updates from his laboratory, revealing details about a three-component therapeutic cocktail currently being tested on mice. Administered as a liquid three days a week over a single month, the treatment produced remarkable physical and cognitive improvements in aged mice. Rather than acting as a short-term stimulant, the cocktail operates by manipulating TET enzymes ($TET1$, $TET2$, $TET3$), which physically erase the methyl groups cluttering the genome. This process effectively rewinds the biological clock and restores youthful cellular function.

> "When you move the hands of the clock, time goes backwards for the body. Meaning the clock is aging. And aging is the clock."

``` THE EPIGENETIC REBOOT CYCLE

The cognitive implications of this molecular "reboot" are profound. Sinclair explains that reversing the age of a mouse's brain restores lost memory functions, suggesting that neurodegenerative conditions like Alzheimer's disease may not destroy memories entirely, but rather block access to them. By reversing the biological age of brain tissue, the body regains its innate ability to repair itself and regain lost functions, just as a young child rapidly heals from physical injuries. Sinclair notes that topical applications of this cocktail applied to the skin of aged mice restored youthful wound healing speed, paving the way for targeted medical and dermatological therapies in humans.

- **Dosing Protocol:** Mice were given the experimental cocktail once a day, three days a week (Monday, Wednesday, Friday), producing measurable physical and cognitive age reversal in 4 weeks. - **TET Enzymes ($TET1, TET2, TET3$):** Specialized proteins responsible for demethylating DNA, essential for resetting cellular age markers. - **Alzheimer's Hypothesis:** Sinclair proposes that memory loss in neurodegenerative diseases may be reversible by restoring youthful cellular state rather than simply treating symptoms.

Here is a detailed, faithful walkthrough of the provided transcript segment:

[47:40](https://www.youtube.com/watch?v=hxid7FofhMw&t=2860s) Lab-Grown Human Hair on Mice and Biohacking Hair Transplants

David Sinclair reveals that his lab is one of the few in the world capable of growing actual human hair on mice, explaining that they engineer it from human stem cells to create little "balls of hair" over several months. They unroll these into flat pieces of human skin and graft them onto mice bred to accept human tissue, resulting in tufts of real black human hair growing out of the rodents. When Joe Rogan jokes about wanting a "Colin Kaepernick type" afro just to mess with people, Sinclair chuckles and confirms they could theoretically grow any hair style. While Sinclair briefly considered commercializing the process, he notes that traditional hair transplants remain simpler.

This leads Rogan to describe his own experience getting a hair transplant, humorously comparing the procedure to moving healthy people into a dying town where everyone else perishes. He points out the biological limitations: patients can only migrate a finite amount of hair from the dense back of their head to the top, which often leaves men with an unnaturally strong hairline up front followed by a chaotic, thinning landscape behind it.

- **Lab process:** Human stem cells are cultured into hair-bearing skin over months and grafted onto specialized immune-compatible mice. - **Instagram controversy:** Sinclair posted a photo of the human-hair-bearing mouse on Instagram, but Harvard immediately ordered him to take it down.

[49:18](https://www.youtube.com/watch?v=hxid7FofhMw&t=2958s) Tadalafil, Nitric Oxide, and New Cancer Research

Sinclair shares his personal hair-preservation strategy: taking a daily low dose of 7 mg of tadalafil (generic Cialis). Beyond hair loss, they discuss how erectile dysfunction (ED) medications function via nitric oxide signaling to dilate blood vessels, which improves overall endurance and cardiovascular health. Sinclair highlights brand-new research showing that these PDE5 inhibitors make mice—and potentially humans—significantly more resistant to specific malignancies like head and neck cancers through two distinct non-vascular mechanisms. First, tadalafil inhibits myeloid-derived suppressor cells (MDSCs) that normally protect tumors from immune attacks, allowing the immune system to shrink the tumor. Second, sildenafil (Viagra) starves cancer cells by blocking their ability to utilize cholesterol.

Rogan recalls that Viagra was originally developed as an angina and blood pressure medication by accident. Sinclair confirms the famous story: male trial participants refused to give back their leftover study pills because roughly 75% experienced dramatic improvements in erection quality compared to just 22% on placebo. When Rogan asks how tadalafil specifically helps hair, Sinclair explains that loss of scalp blood flow is a primary cause of hair follicle death—which is why vasodilator treatments like topical minoxidil work, often paired with oral DHT inhibitors like dutasteride.

- **ED drug cancer benefits:** Tadalafil suppresses tumor-shielding MDSCs; sildenafil blocks cholesterol uptake by cancer cells. - **Dutasteride warning:** Rogan notes a friend developed severe, suicidal depression on DHT blockers that vanished completely as soon as he stopped taking the drug.

[53:20](https://www.youtube.com/watch?v=hxid7FofhMw&t=3200s) Human Clinical Trials and GLP-1 Side Effects

Addressing how therapies are validated for broad human use, Sinclair stresses that individual biological responses vary wildly and all medications require strict medical supervision. Regarding his own lab's gene-therapy research aimed at reversing cellular aging, Sinclair reveals that human clinical trials have already begun by delivering targeted genes directly into the eye. Bound by regulatory restrictions, he carefully notes that "everything's on target" and there is "nothing bad to report." The initial trials target glaucoma as well as non-arteritic anterior ischemic optic neuropathy (NAION)—a form of sudden blindness referred to as an "eye stroke."

Sinclair highlights alarming new data showing that cases of NAION have doubled globally due to the widespread adoption of GLP-1 receptor agonist drugs like Ozempic and Wegovy. Rogan expresses shock, criticizing online influencers and podcasters with financial stakes who blindly promote GLP-1s as risk-free magic bullets.

- **NAION details:** A sudden, painless loss of vision in one eye caused by restricted blood flow to the optic nerve; the condition can subsequently strike the second eye with no known cure. - **GLP-1 risk statistics:** A cited study indicates patients on certain GLP-1 drugs are up to 68.6 times more likely to develop NAION, with an estimated incidence of roughly 1 in 10,000 users.

[57:26](https://www.youtube.com/watch?v=hxid7FofhMw&t=3446s) The Nuance of GLP-1s, Fasting, and Carnivore Diets

Despite the risks, both men acknowledge that GLP-1 drugs have saved millions of lives by curbing severe obesity and food addiction. Sinclair shares a personal story: historically unable to fast for more than a single day due to nighttime snacking cravings, he briefly used a GLP-1 receptor agonist to break his psychological dependence. Once he experienced a successful fast, he discontinued the medication and can now easily complete a two-week fast purely on mental momentum.

Rogan agrees that momentum is the essential companion to discipline when transforming one's life. He explains that his own approach to effortless fasting is maintaining a mostly carnivore-based diet—primarily meat along with fermented vegetables like kimchi and sauerkraut. By avoiding high-carbohydrate spikes and stabilizing insulin, Rogan experiences zero aggressive hunger pangs and can fast 24 hours without effort. Sinclair encourages Rogan to attempt a 3-day fast to trigger chaperone-mediated autophagy (CMA)—a cellular "deep cleansing" process researched by Dr. Ana Maria Cuervo in New York that degrades and recycles old, damaged proteins.

- **Fasting benefits:** Extended fasting triggers CMA to clean out cellular waste, renew internal protein structures, and extend healthspan. - **Ketosis & mental clarity:** Rogan emphasizes that keeping his body in ketosis eliminates brain fog and dramatically sharpens his focus and memory recall during long broadcasts.

[01:01:55](https://www.youtube.com/watch?v=hxid7FofhMw&t=3715s) Exogenous Ketones and Brain Function During Exhausting Workouts

Sinclair relates to the mental exhaustion of hosting solo podcasts, revealing that he must retain hundreds of scientific papers in his head. To combat cognitive fatigue when he cannot fast, Sinclair drinks exogenous ketones like Ketone-IQ. Rogan enthusiastically agrees, sharing that he frequently drinks Ketone-IQ and takes nootropics before commentating live UFC events.

Rogan describes the intense cognitive load of commentating a six-hour live UFC event: constantly analyzing dynamic exchanges, identifying thousands of technical jiu-jitsu positions in real time (such as spotting a Peruvian Necktie), and recounting fighter histories on air. He notes that by the end of a six-hour broadcast, his brain is so thoroughly drained that he experiences ravenous hunger.

- **Cognitive stack:** Rogan relies on Ketone-IQ alongside custom nootropic blends like Gorilla Mind (formulated by his friend Derek) and Alpha Brain Black Label to maintain peak mental sharpness throughout grueling live commentary.

[01:03:32](https://www.youtube.com/watch?v=hxid7FofhMw&t=3812s) Armodafinil, Nootropics, and Beating Jet Lag

Joe Rogan and Dr. David Sinclair discuss the use of wakefulness-promoting agents like modafinil (Provigil) and armodafinil (Nuvigil) alongside other cognitive enhancers. Joe recalls using Provigil and Nuvigil in the past to stay sharp on long night drives after late-night comedy gigs—such as driving two and a half hours back from San Diego at 1:00 AM—noting that unlike caffeine, it allowed him to sleep comfortably once he finally made it home. Sinclair mentions using armodafinil during long-distance travel for international speaking engagements, explaining that it effectively eliminates his jet lag and sharpens his focus when his mind feels scattered.

The discussion shifts to physical strategies for resetting the body clock. Joe explains that his primary cure for severe jet lag is intense exercise that elevates his heart rate to 150–190 BPM for 15 to 20 minutes, such as Tabata sprints on an Airdyne bike or heavy kettlebell circuits. Sinclair agrees that physical exertion functions as a form of hormesis—placing the body under mild, beneficial stress to trigger survival mechanisms.

- **Nootropics & Compounds:** Joe mentions using NeuroGum; Sinclair utilizes armodafinil (Nuvigil) for public speaking and long-haul travel. - **Cardiovascular Protocol:** Joe resets his circadian rhythm via high-intensity intervals (Tabata sprints on the Airdyne bike) aiming for heart rates between 150–190 BPM.

---

[01:06:01](https://www.youtube.com/watch?v=hxid7FofhMw&t=3961s) Fitness, Coaching, and Building Momentum

When Joe asks why Sinclair does not exercise at high intensities despite understanding the biological benefits of hormesis, Sinclair humorously admits that he tells himself he is too busy, though he acknowledges the excuse is invalid. He notes that having an accountable partner or a personal trainer would motivate him to maintain a consistent routine.

Joe offers to become Sinclair's personal trainer in exchange for a supply of Sinclair's health supplements. Joe outlines his training philosophy for sedentary individuals, stressing that workouts should start very light to avoid overtaxing the central nervous system or causing injuries. He emphasizes that consistency and slow progress yield sustainable results, citing his friend Jelly Roll, who began his 250-pound weight loss journey simply by walking around his neighborhood and taking the stairs.

- **Trainer Trade-Off:** Joe jokes about trading fitness coaching services for Sinclair's supplement formulations. - **Gradual Progression:** Joe advises starting with simple movements like 10 push-ups, 10 sit-ups, 10 bodyweight squats, and easy kettlebell cleans rather than training to failure. - **Jelly Roll Example:** Country singer/musician Jelly Roll lost 250 lbs by starting with basic walking, progressive dietary adjustments, and tracking daily progress.

---

[01:09:56](https://www.youtube.com/watch?v=hxid7FofhMw&t=4196s) Plant-Based Diets vs. Carnivore, Blue Zones, and Longevity

The conversation turns to nutrition, specifically Sinclair’s plant-based diet versus Joe's preference for meat. Sinclair explains his framework of two metabolic states: "abundance mode" (pro-growth, muscle-building, driven by nutrient-dense foods like meat) and "adversity mode" (pro-survival, cellular repair, stimulated by plant-derived molecules, fasting, and exercise). While Joe champions red meat and game like elk as the most nutrient-dense foods available, Sinclair expresses openness to trying an elk steak while monitoring his biomarkers.

Joe raises doubts about the popular concept of "Blue Zones"—regions where people supposedly live exceptionally long lives—pointing out that recent analyses suggest widespread census fraud, unrecorded deaths, and pension exploitation (such as in Okinawa, Japan). Sinclair acknowledges that birth and death records in these regions have often proven unreliable, noting that while verified human maximum lifespan reaches around 117–122 years, extreme longevity rarely stems from strict diet alone.

- **Metabolic Framework:** - *Abundance Mode:* Growth, repair, anabolic state, supported by animal protein and high calorie availability. - *Adversity Mode:* Longevity, cellular maintenance, activated by plant compounds, caloric restriction, and exercise. - **Blue Zone Critiques:** Joe highlights findings that many claimed centenarians in blue zones resulted from delayed death reports to continue collecting pension payments. - **Max Human Lifespan:** Sinclair notes verified human maximum lifespan tops out near 117–122 years (referencing Jeanne Calment's disputed record of 122 years in France).

---

[01:12:55](https://www.youtube.com/watch?v=hxid7FofhMw&t=4375s) Relationships, Social Connections, and Biological Aging

Sinclair and Joe discuss how psychological well-being, community, and relationships directly impact biological aging. Sinclair cites a long-running Harvard study led by Dr. Robert Waldinger, which tracked World War II veterans over several decades and determined that the single strongest predictor of health and longevity was having a supportive, loving partner.

Conversely, chronic stress from toxic personal relationships or abusive work environments accelerates biological age by elevating systemic cortisol levels and altering DNA methylation patterns. Sinclair shares that the combined stresses of COVID-19 lockdowns in close quarters led to his own divorce, though he has since rebuilt his life with a new partner who shares his passion for longevity research. He compares human stress responses to his childhood observations of aquarium fish, where targeted, subordinate fish exhibited stunted growth, lost coloration, and died significantly sooner.

- **Harvard Grant/Study on Adult Development:** Led by Dr. Robert Waldinger; identified strong, reliable relationships as the primary determinant of long-term health and survival over traditional physiological metrics. - **Epigenetic Aging & Stress:** Stressful life events like divorces or workplace hostility cause measurable speedups in DNA methylation clocks (epigenetic age). - **Social Dominance Dynamics:** Stress from relational bullying elevates baseline cortisol, impairing repair pathways across species.

[01:17:12](https://www.youtube.com/watch?v=hxid7FofhMw&t=4632s) Longevity Factors, Twitter, and Social Media Stress

Joe Rogan and David Sinclair discuss the lifestyle factors that contribute to a longer life, building on a major longevity study. Beyond healthy relationships, Sinclair highlights four foundational habits: avoiding smoking, refraining from heavy alcohol consumption, getting sufficient rest, and exercising regularly. Together, these core habits can extend a person's lifespan by up to 15 years. Rogan raises the anomaly of chain-smoking, heavy-drinking centenarians. Sinclair explains that such cases represent a tiny fraction—about 0.01%—and are genetic outliers rather than actionable health models. Instead, true centenarians typically share specific psychological traits, notably low stress levels and a strong sense of humor, along with maintaining a healthy body weight and rarely getting sick.

The conversation naturally shifts to the modern drivers of chronic stress, with Rogan wondering "how much time Twitter takes off your life." Both agree that reading social media comments and constantly consuming world news keeps people in a perpetual state of fight-or-flight. Rogan emphasizes that modern humans were not built to process global catastrophes 24/7 while trying to navigate their daily lives. Sinclair adds that the world does not physically change just because one refrains from reading the news, urging people to concentrate on doing good within their immediate sphere of competence rather than carrying the weight of global problems.

- **5 Major Longevity Factors:** Strong relationships, no smoking, no heavy drinking, adequate rest, and regular exercise (yielding up to 15 additional years of life). - **Centenarian Outliers:** Extreme longevity in smokers/drinkers accounts for only ~0.01% of the population. - **Common Traits of Centenarians:** Low stress levels, a good sense of humor, historical lean body weight, and high immune resilience.

---

[01:19:38](https://www.youtube.com/watch?v=hxid7FofhMw&t=4778s) Early Motivations and the Genesis of Sinclair's Research

Addressing the social pressure to fix global issues like climate change, Sinclair recalls an instance where an audience member insisted he should redirect his career toward climate science. His response was simple: "After I cure aging, I'll get to climate change." He explains that his true, lifelong motivation stems from a childhood promise to his grandmother, who escaped Hungary during World War II after surviving the Soviet invasion. When Sinclair was just four years old, she instructed him that humans must strive to make the world a better place. She also bluntly taught him two unsettling truths: that humans can be capable of great evil, and that everyone eventually dies.

That early confrontation with mortality stayed with Sinclair, shaping his life's work. Unlike most children who push the thought of death aside, Sinclair remains acutely aware that approximately 150,000 people die worldwide every day from aging-related diseases. This instills a deep sense of urgency in his Harvard laboratory. He views every delay in research not as a mere setback, but as lost time that could have spared thousands from preventable suffering—explaining why desperate, sick, or visually impaired individuals sometimes show up directly outside his lab seeking early access to experimental therapies.

- **Personal Origin:** Inspired at age 4 by his Hungarian grandmother, a WWII survivor. - **Global Mortality Metric:** ~150,000 people die every day from aging-related conditions. - **Lab Culture:** Driven by a mission-oriented approach where research delays carry real-world human costs.

---

[01:21:47](https://www.youtube.com/watch?v=hxid7FofhMw&t=4907s) AI Breakthroughs in Longevity Science

Sinclair describes how artificial intelligence is radically transforming biological research, shifting his lab's work into hyper-drive. Where scientists previously struggled to keep up with reading 15 research papers a day, AI tools now allow labs to digest and synthesize millions of scientific papers simultaneously. To illustrate this power, Sinclair shares a story about a 19-year-old summer intern in his lab. Sinclair tasked the high school graduate with searching global exabytes of genomic data to test a personal theory: that cells retain an internal biological "master copy" or record of their youthful state in their DNA.

Two weeks later, the intern returned with five senior lab team members to present his findings. Using AI to parse massive biological databases, the teenager found what Sinclair calls the "smoking gun" evidence supporting his theory of cellular memory. Rogan expresses amazement that a teenager with an AI tool accomplished what roomfuls of distinguished professors and decorated scientists could not solve for decades. Sinclair notes that the future belongs to those who know how to leverage AI, predicting that people will soon be designing life-saving medicines—or, worryingly, bioweapons—directly from their smartphones.

- **Research Acceleration:** AI allows processing millions of scientific papers instantly vs. a human maximum of ~15 per day. - **19-Year-Old Intern Discovery:** Used AI over 2 weeks to search exabytes of data and locate evidence for Sinclair's cellular "master copy" memory theory. - **Future AI Applications:** Smartphone-level AI capability to design both advanced pharmaceuticals and potential bioweapons.

---

[01:23:47](https://www.youtube.com/watch?v=hxid7FofhMw&t=5027s) Bioweapon Concerns and Cellular Reversal

Rogan brings up a terrifying recent episode with author Annie Jacobson regarding nuclear and biological warfare risks. Sinclair agrees that bioweapons are a severe threat, revealing that upon moving to the United States, he had to formally disclose to the U.S. government that his expertise gave him the capability to manufacture bioweapons. To aid biodefense efforts, Sinclair maintains a global database tracking known pathogens and emerging biological threats to help the world respond to future pandemics or artificial outbreaks.

The conversation turns back to the therapeutic promise of cellular resetting. Rogan notes that if humans truly possess a factory-reset record in their genome, science could theoretically eradicate all diseases and reverse physical trauma. Sinclair highlights a recent paper demonstrating that two specific genetic factors allowed newborn mice to regrow severed fingertips after the injury had already healed into a stub. He asserts that humans still carry the ancient genetic machinery required to regenerate limbs—much like salamanders—but our evolutionary path favored rapid scar formation over slow limb regrowth. With gene therapy, Sinclair predicts humans may eventually achieve "Deadpool-like" resilience, becoming immune to aging, resistant to injury, and capable of regenerating lost tissue within a couple of decades.

- **Biodefense Disclosures:** Sinclair maintains a specialized pathogen database to help combat potential biological threats and future pandemics. - **Limb Regeneration Breakthrough:** Research showed mouse finger tips can regrow using just two specific genetic factors. - **Future Timeline:** Sinclair estimates practical limb and tissue regeneration in humans could be achievable within two decades.

---

[01:26:37](https://www.youtube.com/watch?v=hxid7FofhMw&t=5197s) The Billionaire Longevity Race and Industry Competition

Rogan asks whether Sinclair feels confident that human age reversal will become a commercial reality. Sinclair expresses immense confidence in the underlying science, noting that while his current clinical trials may or may not hit every milestone, the field itself is unstoppable. He points out that since he founded Life Biosciences to commercialize cellular resetting (using Yamanaka factors like OSK), a massive influx of capital and competing companies has flooded the market.

Sinclair lists major tech figures investing billions into aging research. Jeff Bezos co-founded Altos Labs with multi-billion-dollar funding across three global hubs. OpenAI CEO Sam Altman backed Retro Biosciences, while Coinbase CEO Brian Armstrong founded New Limit. Rogan and Sinclair agree that this fierce competition is fantastic for humanity. Sinclair welcomes the rival labs, emphasizing that his goal isn't personal wealth or glory, but advancing human healthspan globally.

---

[01:28:24](https://www.youtube.com/watch?v=hxid7FofhMw&t=5304s) Engineering Consciousness, Psychedelics, and Ibogaine

Rogan wonders whether science will eventually map the physical brain precisely enough to "engineer consciousness"—curing psychological flaws, sociopathy, or kleptomania by rewiring neural connections. Sinclair confirms that from a biological perspective, mental states are engineering problems that will be addressed this century. However, Sinclair quips that "curing aging is easier than world peace." Rogan argues that expanding human consciousness through psychedelics could accelerate global harmony, citing pharmaceutical giant Eli Lilly’s heavy investment in psychedelic research (including a multi-billion-dollar deal involving ATAI Life Sciences).

Rogan highlights his own advocacy at the White House for an executive order on Ibogaine, explaining how the plant medicine effectively resets the brain for people suffering from severe opioid addiction, traumatic brain injury (TBI), and CTE. Despite its life-saving potential, Ibogaine remains a Schedule I substance in the U.S., which Rogan calls absurd given its lack of recreational appeal and intense 24-hour trip length.

Sinclair and Rogan discuss whether the intense psychological "trip" of psychedelics is necessary to obtain the neurological and therapeutic benefits. Rogan notes that researchers have successfully engineered non-hallucinogenic analogs of LSD and other compounds, preserving the neuroplasticity, cognitive remapping, and therapeutic gains without forcing the patient to undergo a hallucination.

- **Eli Lilly & Psychedelics:** Major pharmaceutical movement into psychedelic-based mental health treatments. - **Ibogaine for Trauma & Addiction:** Highly effective for opioid addiction, TBI, and CTE, despite being an intense 24-hour non-recreational experience. - **Non-Hallucinogenic Analogs:** Scientific progress in modifying molecules like LSD to provide structural neuroplasticity and cognitive benefits without inducing hallucinations.

[01:31:38](https://www.youtube.com/watch?v=hxid7FofhMw&t=5498s) Non-Hallucinogenic Psychedelics and the Search for Truth

Joe Rogan and David Sinclair explore the evolving landscape of psychedelic medicine, comparing how society once refined willow bark into aspirin to how scientists are now refining complex natural compounds into targeted pharmaceuticals. While Rogan points out that pharmaceutical companies often syntheticize natural compounds to profit off patents when the original plant might be superior, Sinclair notes that unapproved plant medicines create a wild-west environment where safety and dosage are completely unregulated. The ideal middle ground is finding fast-tracked, proven-safe therapeutics.

The discussion shifts to a study out of UC Davis where researchers engineered an LSD analog designated as (+)-JRT. By swapping the positions of just two atoms in the LSD chemical structure, scientists created a compound that dramatically reduces or eliminates the hallucinogenic trip while preserving neuroplasticity, synaptic growth, and cognitive benefits. In animal models, (+)-JRT demonstrated profound antidepressant effects—reported to be around 100 times more potent than ketamine—and improved cognitive flexibility in tasks modeling the negative symptoms of schizophrenia.

> "It's almost the same molecule as LSD, but scientists swapped the positions of just two atoms in the structure. The subtle change makes JRT bind more selectively to serotonin receptors in a way that promotes neuroplasticity... but minimizes hallucinogenic signaling."

---

[01:36:01](https://www.youtube.com/watch?v=hxid7FofhMw&t=5761s) AI Bullshit Detectors, Brain Implants, and Global Languages

Joking about how hard it is to spot deceptive podcast guests, Sinclair suggests inventing an AI-powered "bullshit detector" that flashes red or green on someone's forehead. Rogan notes that while he has a strong intuition for people after three-hour conversations, some sociopathic personalities are exceptionally skilled at mimicking normal behavior. Rogan envisions a future where technology allows humans to communicate thoughts directly without spoken language, agreeing with Elon Musk's prediction that Neuralink could allow humans to bypass verbal speech and link into a collective mind.

When discussing global communication and real-time translation headphones, Rogan argues that simple translation often loses cultural context and nuance, making a true universal language ideal. While English currently serves as a global lingua franca, Rogan jokingly hopes Mandarin won't take over, given the extreme difficulty of learning and writing Chinese characters.

- **Translation tech limitations:** Real-time audio translation loses contextual meaning, subtle humor, and cultural nuance across languages. - **Mandarin literacy:** Even fluent non-native Mandarin speakers frequently struggle to learn how to write Chinese characters. - **Neuralink vision:** Bypassing vocal cords to stream thoughts directly between minds could eliminate linguistic friction entirely.

---

[01:38:00](https://www.youtube.com/watch?v=hxid7FofhMw&t=5880s) The American Mindset, Risk-Taking, and the "FU Gene"

Sinclair shares his experience as an Australian living in the United States, expressing deep gratitude for the American culture of venture capital, ambition, and risk-tolerance. In Australia and much of the rest of the world, social norms and fear of losing money inhibit people from launching bold ventures. In contrast, American investors willingly risk capital on big ideas and accept failure as part of the process.

``` +-------------------------------------------------------------------+ | DRD4-7R ("THE RISK GENE") | +-------------------------------------------------------------------+ | • Prevalent in 48% of tested chromosomes across the Americas | | • Present in only ~2% of tested populations in East Asia | | • Strongly correlated with novelty-seeking and risk-taking | | • Upregulated during adolescence to drive independence | +-------------------------------------------------------------------+ ```

Pulling up research via Perplexity, Rogan reads about the **DRD4-7R** gene variant—a dopamine receptor allele linked to novelty-seeking, impulsivity, and financial risk-taking. Studies show that this 7R variant is present in roughly 48% of studied chromosomes in the Americas, compared to only 2% in East Asia, likely selected for as migratory human populations pushed further across the globe. Sinclair labels DRD4-7R the "FU gene," explaining that its expression spikes in teenagers to push them out of the nest by making them challenge authority and leave home.

> "I call this the FU gene because I'm trying to figure out what makes humans special over other animals... It turns out that this gene is turned on in teenagers... It's a way genetically to get them out of the nest."

---

[01:43:50](https://www.youtube.com/watch?v=hxid7FofhMw&t=6230s) Modern Parenting, Resentment, and Guiding the Next Generation

Reflecting on the "FU gene" and teenage rebellion, Rogan and Sinclair discuss how parenting approaches have shifted across generations. Rogan shares his philosophy on raising his daughters: rather than issuing authoritarian commands ("listen to me because I'm your father"), he talks openly about his own past mistakes, emphasizing that he lied and messed up just like anyone else. This creates an environment of empathy rather than resentment.

Sinclair shares an anecdote about working with his 19-year-old son, Benjamin, who spent the summer managing social media for Sinclair's podcast and upcoming magazine. When Benjamin slacked off, Sinclair chose not to reprimand him like a standard boss or scream at him like older generations might have. Instead, he appealed to his son's potential, highlighting his past achievements in calculus and weightlifting, which motivated Benjamin to step up without ruining their close relationship.

- **Authoritarian parenting flaws:** Relying on harsh dominance acts as a blunt instrument that fosters deep resentment and drives kids away. - **Parental vulnerability:** Admitting past personal failures makes advice believable and builds genuine trust. - **Constructive encouragement:** Pointing out a child's past successes encourages accountability far better than anger.

{/* Reason: User may want deeper scientific context on the specific topics discussed in this snippet. */}

Parenting Philosophy, Communication, and Raising Driven Children

Joe Rogan and David Sinclair discuss the philosophy of parenting, emphasizing that parents should act as mentors rather than trying to be strict disciplinarians or "best friends." Sinclair shares that he feels incredibly fortunate with how his children turned out—describing them as smart, ambitious, driven, and talented—and notes that they never went through a phase of teenage rebellion where they hated their parents. Sinclair attributes this positive dynamic to open, empathetic communication where he always admitted his own flaws and early mistakes to his kids from a young age.

Rogan reflects on his own experience, noting that with his first child he imitated his own parents by being overly rigid, which resulted in a more rebellious and distant relationship compared to his later children. They agree that a healthy relationship with ambition is far better than motivating children through fear or strictness, and that exposing kids to the real world—such as bringing them to work to experience entrepreneurship—helps ignite their passion.

* **Parenting Approach:** Treat kids like a mentor rather than a strict authoritarian or a permissive best friend. * **Communication Strategy:** Confess your own past mistakes and foolishness rather than lecturing from a place of perceived perfection. * **Real-World Exposure:** Involve children in work experiences (like Sinclair's son Ben working with him) to show them what is possible and foster intrinsic motivation.

---

Reading Habits, Audio Consumption, and Red Light Therapy for Vision

The conversation pivots to media consumption, reading habits, and vision improvement. Sinclair laments that kids today tend to endlessly scroll social media rather than read books, noting that he subscribes his children to *National Geographic* to keep the art of reading alive. Rogan admits that about 90% of his own content consumption is through audio due to his busy schedule and active lifestyle involving driving, workouts, saunas, hyperbaric chambers, and red light therapy.

This transitions into a detailed discussion about red light therapy. Sinclair shares his personal breakthrough with red light therapy and near-infrared light devices (such as JUVV medical-grade light panels and a full-body bed from Gary Brecka's company), revealing that it completely eliminated his need for reading glasses. He explains the cellular science: light wavelengths stimulate mitochondria, which reverse aging cellular decline and restore energy production in the eye's nerves.

* **Media Consumption:** Rogan relies heavily on audio (podcasts, audiobooks) while multitasking, though he acknowledges reading physical books engages the brain differently. * **Vision Recovery:** Sinclair stopped needing reading glasses (progressing from 1x to 2.5x and then ditching them entirely) after using red light therapy consistently for 20 minutes, 3 to 5 times a week. * **Cellular Mechanism:** Red light and near-infrared wavelengths revive sluggish mitochondria in retinal nerve endings, effectively reminding cells how to function properly.

---

Eye Supplements, Cellular Rejuvenation, and Funding Challenges at Harvard

Sinclair and Rogan discuss eye health supplements like lutein and zeaxanthin (found in products like Pure Encapsulations' macular support), which help protect the retina and prevent degeneration. Sinclair explains the underlying biology of his anti-aging research, noting that around half of the nerve endings in older eyes have merely "forgotten" how to work rather than dying off. By delivering targeted gene therapies, scientists can reboot these cells back to a younger state without turning them into dangerous stem cells.

When Rogan asks about the risks—specifically wondering if making cells younger could trigger cancer—Sinclair reassures him that rigorous animal testing showed no increase in tumors. In fact, research by a PhD student in Sinclair's lab named Natal showed that activating these specific rejuvenation genes inside human cancer cells grown in mice caused the tumors to shrink because the rogue cells recognized they were behaving incorrectly and underwent apoptosis (cell suicide). The conversation concludes with Sinclair sharing a major hurdle: funding for his lab at Harvard Medical School was completely cut the previous year due to political fallout between Harvard and the federal government, forcing them to rely on private donations to keep their research alive.

* **Retinal Health:** Supplements containing lutein and zeaxanthin provide nutritional support for the macula and vision longevity. * **Cellular Reboot:** Aging neurons in organs like the eye are not dead; they can be successfully reminded of their youthful identity through cellular reprogramming. * **Cancer Research:** Activating anti-aging genes in cancer cells can cause them to recognize their abnormal growth and self-destruct. * **Funding Obstacle:** Harvard Medical School lost its federal research funding following political disputes on campus, requiring Sinclair's lab to survive entirely on donations.

By the way, to unlock the full functionality of all Apps, enable [Gemini Apps Activity](https://myactivity.google.com/product/gemini).

[02:00:14](https://www.youtube.com/watch?v=hxid7FofhMw&t=7214s) Funding Longevity Research and Launching Lifespan Magazine

David Sinclair recounts a perilous financial stretch where he nearly had to lay off most of his Harvard laboratory staff due to a lack of federal grant support. Today, his lab survives primarily through private donations, freeing his team from traditional government constraints. Joe Rogan notes that people are eager to fund Sinclair’s work because they recognize his breakthroughs and want to live longer. Sinclair emphasizes his desire to scale up his efforts, testing multiple anti-aging approaches simultaneously across various tissue types rather than relying on a single "shot on goal."

To build a global community and fund ongoing longevity science, Sinclair launched a non-profit foundation accessible via lifespan.com. For a $10 monthly donation, subscribers receive the newly launched *Lifespan* magazine—a publication written directly by scientists rather than journalists to ensure factual accuracy. Sinclair presents Rogan with a special first-edition copy wrapped in a custom velour cover, highlighting the magazine's slogan: "Life's too short. Let's fix that." Sinclair also shares that his lab's research was featured on the cover of *National Geographic* that very day, with the publisher moving up the release date specifically to align with his appearance on the podcast.

- **Website & Foundation:** lifespan.com provides links for tax-deductible foundation donations and community membership. - **Publication Details:** $10/month subscriber model for *Lifespan* magazine, written by credentialed scientists to bypass misleading media reporting. - **Slogan:** "Life's too short. Let's fix that." - **Media Highlight:** *National Geographic* featured Sinclair’s laboratory research on its cover, released early to coincide with the podcast interview.

[02:03:39](https://www.youtube.com/watch?v=hxid7FofhMw&t=7419s) Accelerating Drug Discovery with AI and Robotics

When Rogan asks what could be accomplished without regulatory hurdles or funding constraints, Sinclair laments the frustratingly slow pace of medical development. It took nearly ten years to progress from his laboratory's initial epigenetic reversal discovery published in *Nature* to current human trials—a timeframe he considers tragic given that approximately 150,000 people die worldwide every day from aging-related causes. While artificial intelligence is generating promising drug candidates at unprecedented speeds, testing those molecules through traditional laboratory pipelines creates a massive bottleneck.

Sinclair points to colleagues like Alex Zhavoronkov of Insilico Medicine, whose multi-billion-dollar enterprise uses fully automated robotic labs and AI to advance dozens of candidate molecules into clinical trials rapidly. Sinclair highlights that his own Harvard laboratory operates on a modest budget of roughly $3 million to $3.5 million annually. He argues that boosting funding for longevity science across the field would yield immense global returns, potentially saving trillions of dollars in healthcare expenses in the United States alone.

- **Global Mortality Rate:** ~150,000 deaths occur globally every day, predominantly driven by aging and age-related pathology. - **Lab Budget:** Sinclair’s laboratory operates on approximately $3 million to $3.5 million annually. - **Development Bottleneck:** Standard translational pipelines take roughly 10 years to move a discovery from top-tier journals into human trials. - **Robotic Benchmark:** AI-driven platforms like Alex Zhavoronkov's Insilico Medicine have advanced over 35 AI-designed drug candidates using automated robotic laboratory environments.

[02:07:02](https://www.youtube.com/watch?v=hxid7FofhMw&t=7622s) The Real Cost of Alcohol and Guarding Daily Vitality

Rogan shares a personal story about returning from an overseas trip to Italy jet-lagged, overworking, and experiencing a single day where he felt physically terrible. That experience reminded him how fragile health is and how easily people take baseline vitality for granted. Sinclair notes that chronic illness and old age feel like that every single day, yet healthy young people regularly poison their bodies with alcohol for temporary entertainment. Sinclair explains that he warned his children about alcohol's long-term damage, emphasizing that the body retains a cellular "memory" of heavy drinking. After reviewing brain imaging data proving that consistent drinking shrinks brain volume and accelerates biological aging, Sinclair stopped his daily glass of wine.

Rogan describes taking an eight-month total hiatus from alcohol, which drastically improved his energy and sleep. Although he now occasionally enjoys a single glass of wine or a shot of whiskey before going on stage, he completely avoids getting drunk. For Rogan, the brief novelty of intoxication is not worth sacrificing the energy required for his intense daily workouts. Sinclair agrees, observing that taking control of one's health should become a rewarding hobby rather than a chore, as building physical vitality creates "a bigger gas tank" for every intellectual and creative pursuit.

- **Brain Impact:** Chronic, consistent alcohol intake accelerates biological aging and causes measurable reductions in brain volume. - **Rogan's Abstinence Experiment:** Took 8 months off alcohol entirely; now strictly avoids intoxication to protect his morning workout routine and physical recovery. - **Longevity Mindset:** Framing health optimization as an enjoyable hobby directly increases daily energy, cognitive stamina, and productivity.

[02:10:40](https://www.youtube.com/watch?v=hxid7FofhMw&t=7840s) Optimizing Sleep Hygiene and Tracking Health with Wearables

Sinclair explains that deep sleep triggers the glymphatic system to clear misfolded proteins and metabolic waste from the brain, meaning that even shorter sleep durations can be highly restorative if sleep architecture and deep-sleep efficiency are optimized. Noticing the hardware on Sinclair's hands, Rogan asks why he wears two smart rings. Sinclair explains that he wears a thicker Oura Ring specifically to track sleep metrics and a thinner Ultrahuman ring to monitor cardiac age and heart health, alongside a continuous glucose monitor (CGM) patch on his arm.

Rogan calls Sinclair "fucking monitored," to which Sinclair responds that tracking data provides invaluable feedback. When Sinclair placed a CGM on his son, seeing the immediate blood sugar spikes caused by junk food motivated the boy to transform his diet. They also discuss night-time sleep preparation: Sinclair emphasizes quitting cognitive stimulants like Modafinil, dimming lights hours before bed, steering clear of late-night work stressors, and focusing on calming thoughts. Finally, Sinclair mentions research from Japan showing that staying indoors or blocking natural daytime sunlight can induce myopia (shortsightedness), as the eyes require full-spectrum daylight—including natural blue and violet light—to develop and function properly.

- **Glymphatic System:** Deep sleep actively flushes neurotoxins and misfolded proteins out of the brain's central nervous system. - **Wearable Stack:** Oura Ring (specialized for sleep metrics), Ultrahuman ring (cardiovascular and cardiac age tracking), and a Continuous Glucose Monitor (CGM) for real-time blood sugar tracking. - **Behavioral Biofeedback:** Using continuous glucose monitors helps visually demonstrate the metabolic impact of diet, driving positive behavioral changes in adults and children alike. - **Sleep & Vision Science:** Optimizing sleep requires removing stimulants like Modafinil and dimming lights before bed; conversely, total avoidance of natural daytime light can promote myopia.

[02:14:42](https://www.youtube.com/watch?v=hxid7FofhMw&t=8082s) Screen Fatigue, Eye Strain, and the Mechanics of Vision Loss

David Sinclair brings up a compelling theory regarding light exposure, suggesting that modern artificial indoor lighting—specifically LEDs—deprives people of natural violet and blue wavelengths that are abundant outdoors. He claims that individuals living in rural environments who regularly absorb natural blue light have significantly lower rates of vision deterioration and a reduced need for corrective glasses. Joe Rogan finds this concept logical, adding his own observations about how staring at close-range screens causes severe eye fatigue. Rogan notes that when he is exhausted and attempts to read off his phone in a dark room, his eyes experience noticeable irritation, reflecting the immense strain caused by constantly focusing on near-distance devices like monitors, tablets, and smartphones all day long.

Sinclair elaborates on the mechanical burden placed on the eyes by modern lifestyle habits. The human eye is naturally relaxed when gazing into the far distance, but focusing on an object merely a foot away—such as a book or a digital display—requires the internal ciliary muscles to constantly strain for hours on end. Over time, these muscles fatigue and the ocular lens loses its natural flexibility, leading to progressive vision impairment. Rogan admits to constantly squinting to compensate for fading focus, acknowledging how much sense it makes that modern habits have accelerated age-related vision loss.

- Rural populations exposed to natural outdoor sunlight and blue/violet light display lower rates of corrective lens usage. - Staring at screens at close proximity forces continuous ciliary muscle strain, unlike the natural resting state of long-distance gaze. - Prolonged strain leads to reduced flexibility of the eye's crystalline lens.

---

[02:16:37](https://www.youtube.com/watch?v=hxid7FofhMw&t=8197s) Role Models for Longevity and the Physical Mandate of Strength Training

Sinclair shares the remarkable story of his 87-year-old father, who remains in exceptional health with zero chronic diseases, aches, or pains. Despite having a family history of early mortality and poor genetics, his father transformed his health trajectory around age 60 by adopting a proactive longevity routine that includes taking NMN, resveratrol, and metformin, along with regular exercise. He travels globally—having just visited Japan two weeks prior—and maintains the physical vitality and mobility of a 40-year-old. The only age-related decline he experiences is in his eyesight. Rogan strongly advises Sinclair to buy his father a red light bed, recounting the profoundly positive personal impact red light therapy has had on his own physiological recovery.

The conversation transitions to the imperative need for strength and resistance training, particularly in older adults. Rogan emphasizes that lifting weights maintains bone density and muscle mass, providing the structural integrity required to prevent catastrophic falls late in life. Sinclair agrees, sharing that his father regularly performs strength and balance training at the gym, humorously noting that his father is actually in better physical shape than he is. Rogan playfully challenges Sinclair to hire a personal trainer in Massachusetts for three days a week so that he can return to the podcast significantly more muscular. While joking about his listeners wanting him to focus solely on laboratory research, Sinclair acknowledges his own muscle MRI scan revealed excess intramuscular fat that must be addressed.

- Sinclair's 87-year-old father uses a regimen of NMN, resveratrol, metformin, and regular strength training to maintain 40-year-old-level mobility. - Resistance training is vital for preventing age-related muscle loss (sarcopenia) and preserving bone density. - Rogan advocates for red light therapy as an essential modality for cellular recovery and tissue health.

---

[02:19:51](https://www.youtube.com/watch?v=hxid7FofhMw&t=8391s) Hypoxic Training, Hormesis, and Oxygen Modulation Protocols

Rogan describes his newest fitness equipment installation: a specialized hypoxic conditioning chamber. The machine simulates an altitude of 14,000 feet above sea level while ramping heat up to 115°F (46°C) to create an intense environmental stressor. Guided by specific protocols designed by his friend Roman and recommended by Australian hunter Adam Greentree, Rogan tracks his heart rate closely to optimize cardiorespiratory adaptations. Sinclair notes that the underlying science relies heavily on hormesis—the biological process where mild, brief environmental stressors trigger cellular repair and adaptation mechanisms.

Sinclair references a prominent Israeli study on hyperbaric oxygen therapy (HBOT) protocols involving 60 sessions over 90 days. While HBOT saturates tissues with hyperbaric oxygen, both hosts agree that the core biological trigger may actually be the perceived oxygen deficit—or relative hypoxia—that occurs when oxygen concentration drops back down to normal levels. This physiological signal triggers cellular pathways similar to severe exercise, driving the growth of new blood vessels and cellular restoration.

- High-altitude hypoxic chambers simulate 14,000 feet above sea level alongside heat exposure up to 115°F to spur cardiovascular adaptation. - Clinical hyperbaric oxygen therapy (HBOT) protocols (e.g., 60 90-minute sessions over 90 days) have demonstrated measurable improvements in wound healing, memory performance, and telomere lengthening. - The mechanism of relative hypoxia drives physiological vascular remodeling and tissue repair through hormetic signaling.

---

[02:22:27](https://www.youtube.com/watch?v=hxid7FofhMw&t=8547s) Microvascular Health, Dementia Prevention, and Closing Remarks

Sinclair addresses the critical yet under-discussed role of vascular health in aging. He highlights that reduced cerebral blood flow is the primary cause of vascular dementia—the second most common form of dementia globally. Maintaining robust microvascular circulation is one of the most actionable ways to protect cognitive function in old age. Sinclair mentions a 2012 study from his lab demonstrating that NMN administration helped animals generate new blood vessels by clearing age-accumulated protein blockages.

To maintain healthy microcirculation and combat age-related vascular decline, Sinclair outlines three synergistic interventions: physical exercise, phosphodiesterase-5 (PDE5) inhibitors like Sildenafil (Viagra), and NAD+ precursors like NMN. Sinclair quips that he is currently doing "two out of three" of these strategies, with plans to incorporate the third soon. Rogan stresses that preserving brain health and cerebral blood flow is the ultimate goal of longevity science, as cognitive decline represents the most devastating aspect of aging. The episode concludes with mutual expressions of respect, with Rogan praising Sinclair’s ground-breaking research and encouraging listeners to support longevity science efforts through lifespan.com.

- Vascular dementia, driven by impaired blood flow to the brain, represents the second leading cause of dementia worldwide. - Interventions that enhance microvascular integrity include aerobic/resistance exercise, PDE5 inhibitors (Viagra), and NMN supplementation. - A 2012 study showed NMN promotes new blood vessel formation by removing toxic protein buildup associated with vascular aging.

## Notable quotes > [01:31:38](https://www.youtube.com/watch?v=hxid7FofhMw&t=5498s) It's almost the same molecule as LSD, but scientists swapped the positions of just two atoms in the structure. The subtle change makes JRT bind more selectively to serotonin receptors in a way that promotes neuroplasticity... but minimizes hallucinogenic signaling. — David Sinclair

> [01:36:00](https://www.youtube.com/watch?v=hxid7FofhMw&t=5760s) I call this the FU gene because I'm trying to figure out what makes humans special over other animals... It turns out that this gene is turned on in teenagers... It's a way genetically to get them out of the nest. — David Sinclair

> [02:00:14](https://www.youtube.com/watch?v=hxid7FofhMw&t=7214s) Life's too short. Let's fix that. — David Sinclair

## Mentioned David Sinclair, Joe Rogan, Harvard University, Harvard Medical School, Cialis, Viagra, Ozempic, Wegovy, Colin Kaepernick, Ana Maria Cuervo, Ketone-IQ, Gorilla Mind, Alpha Brain Black Label, NeuroGum, Jelly Roll, Jeanne Calment, Robert Waldinger, Annie Jacobson, Life Biosciences, Altos Labs, Jeff Bezos, Retro Biosciences, Sam Altman, New Limit, Brian Armstrong, Eli Lilly, ATAI Life Sciences, Neuralink, Elon Musk, Gary Brecka, DRD4-7R, (+)-JRT, Natal, Alex Zhavoronkov, Insilico Medicine, Roman, Adam Greentree, Pure Encapsulations, Oura Ring, Ultrahuman, Lifespan, National Geographic, Nature, Modafinil, NMN, resveratrol, metformin, Sildenafil

[Source](https://www.youtube.com/watch?v=hxid7FofhMw)

中文简报

David Sinclair指出GLP-1药物与眼中风风险翻倍相关哈佛大学遗传学家David Sinclair警告称，GLP-1减肥药的广泛应用使非动脉炎性前部缺血性视神经病变病例增加了一倍，与此同时，他的实验室正在推进旨在逆转细胞衰老和组织流失的基因疗法。 David Sinclair博士与Joe Rogan共同探讨了前沿的长寿科学，讨论了细胞逆转疗法、针对视力丧失的基因疗法试验，以及(+)-JRT和PDE5抑制剂等新型化合物在延长健康寿命中的作用。他们分析了有助于降低生物学年龄的可行生活习惯，包括断食、力量训练、睡眠卫生和戒酒。此外，对话还涉及了AI对医学研究的变革、人类冒险行为的遗传根源，以及GLP-1药物广泛的系统性影响。 Sinclair 实验室成功利用人类干细胞在免疫相容小鼠身上培育出真正的人类头发，验证了生物工程毛发生长的可行性。 (47:40) 研究显示每日小剂量服用他达拉非等 PDE5 抑制剂不仅改善血流有助防脱发，还能抑制保护肿瘤的骨髓源性抑制细胞（MDSC），增强机体抗癌免疫。 (49:18) 针对青光眼和非动脉炎性前部缺血性视神经病变（NAION）的表观遗传重编程眼部基因疗法已开启首批人体临床试验；与此同时，GLP-1 药物的广泛使用导致 NAION 发病率翻倍。 (53:20) Sinclair 团队借助 AI 与 AlphaFold 数据库对上万亿种分子进行虚拟高通量筛选，将长达 160 年的传统药物研发周期压缩至两个月。 (26:13)

Reading summary

Harvard geneticist Dr. David Sinclair argues that biological aging is driven by reversible epigenetic degradation rather than permanent deterioration, asserting that cellular age can be safely reset through targeted reprogramming factors, AI-accelerated drug discovery, and vascular support. While early human trials and preclinical models demonstrate tissue regeneration, Sinclair emphasizes that regulatory friction, funding constraints, and dual-use biosecurity risks complicate broad clinical adoption. Cellular Reprogramming and the OSK Factor Pipeline (5:26) Sinclair frames biological aging as a loss of cellular identity tracked by DNA methylation patterns rather than structural loss of genetic code. Building on Shinya Yamanaka's Nobel Prize-winning stem cell research, Sinclair's laboratory developed a three-factor cocktail—OCT4, SOX2, and KLF4 (OSK)—that explicitly omits the oncogenic c-MYC gene. This approach resets cellular age by roughly 75% to 80% without converting differentiated adult cells into unspecialized, tumor-prone pluripotent stem cells. Following preclinical demonstrations of optic nerve regeneration and joint cartilage repair in rodent models, the first human clinical trial is actively underway. Delivered via an engineered adeno-associated viral (AAV) vector injected directly into the eye, the treatment (designated ER100 or OSK) targets vision loss resulting from glaucoma and non-arteritic anterior ischemic optic neuropathy (NAION). Sinclair notes that the trial is proceeding under FDA oversight with zero adverse safety issues reported in initial human subjects. AI Virtual Screening and Dual-Use Biosecurity (26:13) To bypass decades of manual laboratory screening, Sinclair's laboratory utilizes high-performance computing clusters and Google DeepMind's AlphaFold structural protein database to evaluate drug candidates virtually. Collaborating with St. Jude Children's Research Hospital, the team docked a virtual library of roughly one trillion molecules against intracellular enzymes to identify compounds capable of activating multiple anti-aging pathways simultaneously, condensing an estimated 160 years of bench research into two months and isolating 200 high-priority leads. Despite computational acceleration, Sinclair notes that physical validation through traditional wet labs remains a major developmental bottleneck. Moreover, the dual-use potential of genetic and longevity engineering has triggered national security oversight. Sinclair discloses that U.S. regulatory authorities intervened to block a $160 million foreign investment into one of his biotechnology firms due to defense concerns regarding advanced human enhancement and the proliferation of dual-use biological technologies. Repurposed Compounds and Engineered Neuroactive Molecules (49:18) Beyond gene therapy, the dialogue reviews existing pharmaceuticals repurposed for longevity and cognitive enhancement. Sinclair details his daily regimen of low-dose tadalafil (7 mg), explaining that PDE5 inhibitors enhance microvascular perfusion and show preclinical promise in suppressing myeloid-derived suppressor cells (MDSCs) that shield tumors from immune surveillance. In contrast, Sinclair highlights emerging safety signals regarding GLP-1 receptor agonists, citing clinical studies showing an up to 68.6-fold relative risk increase for NAION-induced blindness, affecting roughly 1 in 10,000 users. Turning to neurological maintenance and psychological resilience, Rogan and Sinclair examine neuroplastic therapeutics and non-hallucinogenic psychedelic derivatives. Sinclair points to research from UC Davis involving (+)-JRT, an engineered analog of LSD. By altering two atomic positions, researchers eliminated the hallucinogenic response while preserving 5-HT receptor-mediated synaptogenesis and demonstrating potent antidepressant properties in animal models. Microvascular Health, Hormetic Stressors, and Daily Habits (142:27) Sinclair highlights cerebral microvascular decline as the underlying mechanism driving vascular dementia, the second most common form of dementia globally. To protect microcirculation, he outlines three synergistic interventions: physical resistance training, PDE5 inhibitors, and NAD+ precursors such as NMN. He couples these with hormetic stressors—controlled environmental challenges that trigger cellular repair pathways—including extended fasting to induce chaperone-mediated autophagy (CMA), hypoxic training, and red-light phototherapy, which Sinclair claims eliminated his dependence on reading glasses by restoring ocular mitochondrial function. At the behavioral level, Sinclair and Rogan emphasize foundational lifestyle factors over extreme biohacking. Referencing the multi-decade Harvard Study of Adult Development, Sinclair identifies supportive social relationships as the single strongest statistical predictor of human lifespan. He adds that basic habits—abstaining from heavy alcohol use, maintaining regular strength training to preserve bone density, and optimizing deep sleep for glymphatic waste clearance—can add up to 15 years of healthspan. While Sinclair maintains that aging will eventually be treated as an addressable medical condition, substantial limitations persist. These include the financial vulnerability of academic research—exemplified by federal funding cuts that forced his Harvard lab to depend on private philanthropy—the unresolved regulatory gap between automated drug discovery and long-term human validation, and the challenge of scaling advanced genetic therapies safely beyond localized ocular tissues.

精炼阅读摘要

哈佛大学遗传学家戴维·辛克莱（David Sinclair）在访谈中指出，衰老是由表观遗传信息丢失引起的单一可控生理过程，可通过特异性细胞重编程技术实现安全逆转；结合人工智能分子筛选、微血管靶向干预与激效生活方式，人类有望实现系统性机能年轻化，但该领域仍面临监管滞后、伦理审查与科研资金断层的多重挑战。表观遗传重编程与OSK人体临床试验 (5:26) 辛克莱阐述了衰老的表观遗传信息损耗假说：细胞并未丧失原始基因组序列，而是如同划痕的光盘般失去了读取正确软件的能力。通过借鉴诺贝尔奖得主山中伸弥的研究并剔除致癌基因c-Myc，辛克莱团队开发出由Oct4、Sox2与Klf4组成的“OSK”三因子鸡尾酒疗法（代号ER100）。该疗法能将细胞表观遗传年龄重置75%至80%，恢复细胞分化身份与年轻功能，而不会诱导细胞退回多能干细胞状态或形成肿瘤。生物学年龄的逆转程度则通过精确追踪DNA甲基化模式（DNA Methylation Clocks）进行量化。在完成小鼠与非人灵长类动物实验后，首项经FDA批准的人体临床试验已正式启动。研究人员利用经过表面蛋白改造的工程化腺相关病毒载体（AAV），将重编程基因直接注入青光眼及非动脉炎性前部缺血性视神经病变（NAION，即眼中风）志愿者的眼部玻璃体腔内。辛克莱表示首批人体注射未观察到不良安全性事件。此外，中国独立科研团队利用OSK技术成功促使关节炎小鼠模型受损的肌肉与骨骼组织完全再生，证实该机制在运动创伤与退行性骨关节炎修复中具备广泛临床转化前景。 AI超大规模分子筛选与双重用途伦理 (26:13) 计算机算力与人工智能正在颠覆传统长寿科研的研发周期。辛克莱实验室结合DeepMind的AlphaFold蛋白质三维结构数据库（涵盖超20,000种人类蛋白），与圣犹达儿童研究医院合作，对包含约1万亿个候选化合物的虚拟库展开高通量分子对接筛选，旨在寻找能同时触发多重抗衰靶点的单分子口服药，成功将研发筛选周期从传统人工台架实验的160年缩短至两个月，最终锁定约200个高潜力先导化合物进入人源细胞测试。实验室一名19岁实习生利用AI解析全球基因组海量数据，亦在两周内挖掘出支持细胞留存年轻记忆主拷贝的关键证据。然而，生命工程技术的飞跃也伴随着严峻的生物安全与国家安全博弈。辛克莱透露，美国监管机构此前曾出于防范制造“超级士兵”以及敏感双工基因技术外流的考量，叫停了一笔针对其生物技术公司的1.6亿美元外国投资。由于AI同样存在被用于低门槛设计合成致命病原体的风险，辛克莱已向美国政府报备其具备制造生物武器的专业知识，并协同维护全球病原体防御数据库以防范潜在生物袭击。微循环保护、代谢调节与靶向药理探索 (49:18) 辛克莱强调，微血管退化与脑血流灌注不足是引发血管性痴呆（全球第二大痴呆病因）的核心推手，维护血管微循环是保护大脑认知与生理活力的刚需。他提出三联血管保护策略：规律运动、补充NAD+前体（如NMN促进毛细血管新生）以及低剂量5型磷酸二酯酶（PDE5）抑制剂。辛克莱自述每日服用7毫克他达拉非（Tadalafil），不仅通过一氧化氮途径改善头皮血流以维系毛囊活力，最新肿瘤学研究还表明该类药物能抑制保护肿瘤的髓系抑制细胞（MDSCs），而西地那非则可阻断癌细胞利用胆固醇，两者在动物实验中均表现出抑制头颈部恶性肿瘤的效果。在代谢干预层面，辛克莱将机体划分为高蛋白支持生长的“丰裕模式”与激发细胞防御修复的“逆境模式”。针对风靡全球的GLP-1受体激动剂（如Ozempic与Wegovy），辛克莱肯定其阻断食物成瘾的价值，但援引流行病学数据指出该类药物使NAION突发致盲风险增加了最高达68.6倍（发病率约万分之一），强调需严格在医疗监控下使用。对于禁食机制，辛克莱建议进行为期3天的深度禁食，以激活分子伴侣介导的自噬（CMA），彻底清除细胞内堆积的变性蛋白与代谢垃圾。激效压力、生活方式与心理健康干预 (72:55) 非药物层面的行为干预对表观遗传时钟具有显著调控作用。辛克莱援引哈佛大学成人发展研究（Dr. Robert Waldinger主导）长达数十年的追踪数据指出，拥有支持性、充满爱的亲密伴侣是预测人类长期健康与寿命的最强指标；相反，不良人际关系与持续毒性压力会显著拉高皮质醇水平并加速DNA甲基化时钟。不吸烟、不酗酒、规律运动与充足睡眠四大支柱习惯，累计可延长个体约15年健康寿命；深度睡眠期间启动的脑部类淋巴系统（glymphatic system）能高效清除淀粉样沉积等神经毒素。此外，合理利用“激效”（Hormesis，即温和急性应激诱导机体代偿防御）是激活生存回路的关键载体。辛克莱通过每周3至5次、每次20分钟的红光与近红外光疗法刺激视网膜线粒体能量生成，成功逆转了自身视力衰退并彻底摆脱老花镜；罗根则采用14,000英尺模拟海拔伴随115°F高温的极端低氧舱进行心肺适应训练。研究还显示，高压氧疗法（HBOT）在恢复常氧状态后产生的“相对缺氧信号”同样能强效驱动血管内皮生长因子释放。对于老年群体，辛克莱列举其87岁依然体力充沛的父亲为例，强调大重量阻抗力量训练对维持骨密度、预防晚年致命性跌倒具有不可替代的生理刚性。辛克莱强调，衰老相关疾病每日在全球夺走约15万人的生命，延缓衰老研发具备重大的公共卫生与经济价值。然而，科研资金链断裂构成了严峻现实阻碍——其实验室曾因联邦经费削减一度面临裁员危机，目前高度依赖私人捐赠与自主创立的《Lifespan》基金会维系运转；加之药物临床转化监管周期长达数年，如何打破传统审批壁垒并实现低成本规模化普及，仍是抗衰老医学亟待解决的核心难题。

Detailed notes — zh

## Background 本期节目于 2026 年 8 月 24 日由 PowerfulJRE 频道在 YouTube 平台发布。嘉宾戴维·辛克莱尔（David Sinclair）是哈佛医学院遗传学教授、知名长寿科学家、《可不可以不变老》（Lifespan）一书作者及同名播客主持人，节目简介聚焦于衰老机制研究与逆转衰老的前沿探索。 ## TL;DR 辛克莱尔深入阐述了表观遗传重编程与肢体再生的前沿前景，并剖析了百亿资本涌入抗衰研发赛道对行业拐点的推动作用。对话涵盖了无致幻神经可塑性药物研发、视网膜神经元逆转失明及肿瘤抑制的意外突破，以及结合 AI 与自动化机器人加速研发周期的必要性。此外，辛克莱尔结合日常佩戴的监测设备与其实验室研究，详细分享了红光疗法、抗阻力量训练、NMN 及改善微循环对延缓大脑和机体衰老的科学实践。 ## Atmosphere & style 整场对话在硬核前沿生物科学与直率极客探索的碰撞中展开，罗根充满好奇与务实追问的提问风格，与辛克莱尔饱含激情且严谨的学者视野形成了鲜明互补。对谈既有对人类攻克衰老这一宏大命题的紧迫感与使命感，又穿插着关于亲子教育、戒酒、健身赌约等充满烟火气的个人坦白。整期节目节奏张弛有度，听众既能感受到未来医学革命前夜的智识震撼，又能体会到挚友间真诚交流的松弛与温度。 ## Bulletin - [01:31:27](https://www.youtube.com/watch?v=hxid7FofhMw&t=5487s) 加州大学戴维斯分校合成无致幻 LSD 类似物 (±)-JRT，仅改变分子中 2 个原子位置便剥离致幻信号，在啮齿动物模型中展现出约为氯胺酮 100 倍的抗抑郁药效并能强烈激活突触生长。 - [01:24:21](https://www.youtube.com/watch?v=hxid7FofhMw&t=5061s) 表观遗传重编程研究显示，仅需两种转录因子即可诱导幼年小鼠愈合指端重新长出部分指节，表明人类基因组完好保留着年轻发育潜能。 - [01:57:02](https://www.youtube.com/watch?v=hxid7FofhMw&t=7022s) 重编程因子实验出现意外抗肿瘤发现：将重编程因子导入小鼠体内的人类癌细胞后，癌细胞重新识别自身的异常分裂并主动启动凋亡程序，促使肿瘤萎缩。 - [02:22:41](https://www.youtube.com/watch?v=hxid7FofhMw&t=8561s) 针对全球第二大痴呆类型血管性痴呆，辛克莱尔指出补充 NMN、规律体育锻炼以及使用 PDE5 抑制剂（伟哥）是促进血管内皮细胞新生与改善大脑灌注的三大途径。 ## Key takeaways - [01:24:21](https://www.youtube.com/watch?v=hxid7FofhMw&t=5061s) 人类基因组完整保留了年轻健康的原始备份，表观遗传重编程如同出厂重置，有望在未来数十年内实现复杂哺乳动物肢体再生的临床突破。 - [01:26:48](https://www.youtube.com/watch?v=hxid7FofhMw&t=5208s) 百亿资本正加速涌入细胞重编程赛道，Altos Labs、Retro Biosciences 及 NewLimit 等巨头机构的介入正将抗衰老医学推向工业化拐点。 - [01:28:24](https://www.youtube.com/watch?v=hxid7FofhMw&t=5304s) 去致幻化神经药物研发迎来技术转折，科研人员正致力于将伊博格碱等物质的致幻体验与神经可塑性修复机制在分子层面彻底剥离。 - [01:31:27](https://www.youtube.com/watch?v=hxid7FofhMw&t=5487s) LSD 衍生分子 (±)-JRT 能够在完全不触发致幻回路的前提下激活神经突触修复，并能显著改善模拟精神分裂症的认知缺失。 - [01:41:00](https://www.youtube.com/watch?v=hxid7FofhMw&t=6060s) 多巴胺受体变异基因 DRD4-7R 与探索新奇及高风险决策紧密相关，其人群分布频率与人类祖先走出非洲的迁徙距离呈显著正相关。 - [01:51:42](https://www.youtube.com/watch?v=hxid7FofhMw&t=6702s) 特定波长的红光与近红外光能够穿透组织刺激眼部细胞线粒体合成 ATP，临床与个体实践表明其能有效缓解或逆转睫状肌疲劳与老花眼症状。 - [01:57:02](https://www.youtube.com/watch?v=hxid7FofhMw&t=7022s) 衰老视神经元大多并未真正死亡而是遗忘了细胞身份，三因子重编程技术在逆转失明的同时未诱发脱分化干细胞或畸胎瘤。 - [02:03:39](https://www.youtube.com/watch?v=hxid7FofhMw&t=7419s) 全球每天约有 15 万人死于衰老相关疾病，引入自动化机器人与生成式 AI 闭环研发是打破长达十年临床周期的必然选择。 - [02:07:33](https://www.youtube.com/watch?v=hxid7FofhMw&t=7653s) 长期饮酒会导致脑容量实质性萎缩，深度睡眠期间启动的脑内胶质淋巴系统则是清除代谢废物与错误折叠蛋白的核心防御机制。 - [02:16:40](https://www.youtube.com/watch?v=hxid7FofhMw&t=8200s) 抗阻力量训练是防止高龄人群肌少症和跌倒的关键，能够有效消除久坐导致的老年人肌肉内部严重脂肪浸润。 - [02:19:51](https://www.youtube.com/watch?v=hxid7FofhMw&t=8391s) 高压氧舱（HBOT）刺激血管新生的核心生物学机制并非单纯高压环境，而是减压恢复常压过程中机体感受到的相对低氧激效反应（hormesis）。 - [02:22:41](https://www.youtube.com/watch?v=hxid7FofhMw&t=8561s) 大脑血流灌注不足是引发血管性痴呆的根源，通过 NMN 补充、有氧运动和 PDE5 抑制剂协同干预可激活全身与脑血管内皮修复。 ## Detailed walkthrough ### [00:12](https://www.youtube.com/watch?v=hxid7FofhMw&t=12s) 澳洲爵位趣谈、“高罂粟综合征”与健康咖啡节目开场，乔·罗根（Joe Rogan）热情欢迎大卫·辛克莱（David Sinclair），并随口称呼他为“辛克莱先生”，辛克莱随即开玩笑纠正道是“辛克莱博士”。但辛克莱紧接着坦承，自己在日常生活中其实从不用“博士”头衔自称。不仅如此，他还提到自己因为对科学的贡献获得了“澳大利亚勋章”（Order of Australia, AO），在澳洲理论上相当于拥有类似骑士爵位的认可。辛克莱打趣说，虽然名字后面可以加上“AO”头衔，有时也被戏称为“大卫爵士”，但这在实际生活中并无任何实质特权，“就像在加油站碰到任何人都能随口喊一声 Sir 一样”，只多了几个字母而已。两人随即聊起了澳大利亚独特的文化氛围。辛克莱指出，在澳洲文化中，如果一个人表现得自命不凡、自吹自擂，从小就会在操场上挨揍。罗根对此深表认同，提到澳大利亚极为盛行的“高罂粟综合征”（Tall Poppy Syndrome）——社会容不得任何人自傲出格，大家极力拉平优越感。辛克莱表示自己非常喜欢回澳洲，正因为那里是一个绝对平等的竞技场，没有任何人会在意你的显赫头衔。聊到跨洋飞往澳洲的漫长旅程时，罗根回忆起以前人们常用的“威士忌配安眠药（Ambien）”入睡法，而辛克莱则透露自己如今已彻底戒除酒精，除非极罕见的庆祝场合，平时滴酒不沾。罗根为辛克莱准备了一杯由冲浪传奇莱尔德·汉密尔顿（Laird Hamilton）旗下品牌 Laird Superfood 与 Black Rifle Coffee 联名制作的特调咖啡。这杯咖啡融入了姜黄（turmeric）与椰奶等超级食物成分，不仅风味浓郁，还具备出色的抗炎功效。辛克莱笑着称赞这杯饮品完美契合理念，罗根顺势戏称他是“长寿先知”（Prophet of Longevity）。 ### [02:40](https://www.youtube.com/watch?v=hxid7FofhMw&t=160s) 《长寿》畅销奇迹与全民长寿热潮的兴起辛克莱对第四次受邀登上 JRE 播客向罗根表达了由衷的感谢。他回顾了两人首次结缘的契机：2019 年他在节目中宣传自己的新书《长寿：为什么我们会衰老，为什么我们不必衰老》（Lifespan: Why We Age—and Why We Don't Have To）。得益于播客的巨大传播力，这本原本充满了高深技术细节与前沿科学理论的专著在全球掀起热潮，被翻译成 40 多种语言，阅读量达到数百万人次，跃居全球畅销书之列。辛克莱强调，写书本身并不赚钱，但能让晦涩的前沿科学进入大众视野，具有里程碑式的意义。罗根与辛克莱深入探讨了近年来全社会对“长寿与健康优化”关注度激增的原因。辛克莱认为，除了书籍与播客的普及，2019 年底爆发的新冠疫情是关键转折点。在此之前，绝大多数 70 岁以下的人几乎从未认真审视过自身的死亡与衰弱；但突如其来的全球危机让无数人猛然意识到“原来我随时可能死去”，进而催生了强烈的自我健康管理意识。罗根观察到，如今大众对各类干预手段极为狂热——冷水浸泡（cold plunge）、红外桑拿、红光疗法（red light therapy）以及各种生物黑客协议（biohacking protocols）已经成为日常谈资。罗根强调，长寿的真谛并不在于单纯苟延残喘地延长生物学寿命，而在于改善当下的生存质量；只有当下状态得到优化、精力充沛，长寿才会作为水到渠成的副产品自然发生。辛克莱十分赞同这一观点，并指出普通人其实不必把长寿想得过于复杂，只要在日常生活中坚持做好或避免 5 件基础的生活习惯，就有可能无痛延长约 15 年的健康寿命。 - **《长寿》一书的影响力**：2019年出版后全球读者超数百万，翻译达 40 余种语言。 - **心理转折**：全球疫情迫使 70 岁以下的中青年人群直面个体脆弱性与死亡风险。 - **生活干预的核心逻辑**：通过 5 种基础生活方式调整，即可争取额外 15 年的健康寿命（Healthspan）。 ### [05:08](https://www.youtube.com/watch?v=hxid7FofhMw&t=308s) 从科学异端到人体试验：逆转衰老的细胞“重装系统” 谈到前沿科技的进展，罗根询问目前的衰老干预手段究竟走到了哪一步。辛克莱感慨地指出，自 2019 年他们首次在播客上讨论衰老逆转以来，许多当年被视为天方夜谭的设想如今已悉数变成现实。彼时，任何科学家如果敢在公开场合宣称“衰老可以被逆转”，都会被主流学界视作离经叛道的“异端”。然而时至今日，衰老逆转不仅在小鼠实验室和非人灵长类（猴子）身上得到了确凿验证，甚至已经正式跨入了人类临床试验阶段。罗根提出，既然人类已经逐渐掌握衰老的底层分子机制，试图去逆转它在逻辑上是完全成立的，过去学界的禁锢反倒令人费解。辛克莱解释说，过去千百年里人类对衰老持妥协态度，就像两百年前医学界对癌症束手无策一样，认为衰老是不可抗拒的自然规律。但现代遗传学与表观遗传学研究表明，全身几乎所有细胞的衰老都共享着同一个根本原因（Root Cause）。辛克莱及其团队在 2020 年发表的重要论文中证实，衰老并非不可逆的单向磨损，细胞内部依然保留着年轻时期的初始信息。通过激活特定的基因组合，科学家可以安全地重置细胞的表观遗传时钟，这就像给出现严重软件错误的计算机“重新安装操作系统”一样，使衰老失能的细胞重获青春并恢复原有功能。 ```mermaid flowchart TD accTitle: 细胞表观遗传衰老与重编程恢复机制 accDescr: 展示从年轻健康细胞到表观遗传信息紊乱的衰老细胞，再经由特定基因重新激活、恢复为年轻细胞的过程。 subgraph AgingProcess["衰老阶段"] A["年轻健康细胞 （表观遗传软件完好）"] --> B["环境压力与DNA损伤累积"] B --> C["表观遗传信息紊乱 （衰老失能细胞）"] end subgraph RejuvenationProcess["重编程重置阶段"] C --> D["导入转录因子组合 （如 OSK / ER100）"] D --> E["重装细胞系统 （重置表观遗传标记）"] E --> F["恢复年轻生理功能 （细胞逆龄工作）"] end ``` ### [06:41](https://www.youtube.com/watch?v=hxid7FofhMw&t=401s) 病毒载体递送系统（ER100 / OSK）与青光眼人体试验为了向罗根直观解释这项前沿疗法，辛克莱从口袋里掏出了一个实物教具模型：一个带有多处凸起突刺的橡胶球，外观类似于新冠病毒颗粒。辛克莱笑着打消罗根的疑虑，解释这绝非致病病毒，而是一种在实验室中被驯化改造的病毒载体外壳（基于腺相关病毒 AAV 设计）。辛克莱详细拆解了这一递送系统的工作原理： 1. **靶向转运适配器**：病毒载体表面的突刺小球充当“导航雷达”，可以精准识别并附着在特定组织的细胞受体上。当前正在进行的人体试验将表面突刺定制为靶向眼球后部的视网膜细胞；若改变表面蛋白突刺，便可靶向递送至肝脏（实验室已利用该技术成功治愈了小鼠的脂肪肝疾病）。 2. **基因载荷（Payload）**：在蛋白质外壳内部包裹着特定的重编程基因载荷，该疗法被命名为 **ER100**（即 Epigenetic Reprogramming 100，表观遗传重编程 100 号）或经典因子组合 **OSK**（Oct4、Sox2、Klf4，去除了具有致癌风险的 c-Myc）。辛克莱透露，首例人体临床试验已于今年早些时候正式给药。受试者是一位因青光眼导致视力丧失、单眼几乎完全失明的志愿者。由于常规医学已经宣判其视力无法挽回，该患者勇敢地选择成为人类历史上第一位接受这种重编程基因疗法的人，眼球内被单次注射了数万亿个病毒载体颗粒。辛克莱欣慰地表示，截至目前，临床监测显示未出现任何不良安全性问题，一切均在按预定计划平稳推进。若该试验最终成功逆转视神经细胞年龄并恢复视力，将成为整个人类医学史的划时代转折点。听到这里，罗根忍不住大笑并调侃道，这简直就是典型好莱坞丧尸灾难片（如《惊变28天》/ *28 Days Later*）的标准开场白：电视节目里，一位斯文优雅的科学家正端着咖啡向观众娓娓道来“我们正在利用病毒载体逆转衰老，大家不必惊慌”；画面一转，28 天后主角从昏迷中醒来，大街上满地废墟、汽车起火燃烧，这群被所谓“优化”的人类已经异变成了互相啃噬的丧尸。辛克莱对此也忍俊不禁，坦承这门前沿技术在公众眼中的确极具未来科幻甚至带有惊悚色彩。 ### [09:34](https://www.youtube.com/watch?v=hxid7FofhMw&t=574s) 眼睛基因疗法与体内“青春备份”的重启机制辛克莱（David Sinclair）解释了为何人体临床试验选择从眼睛切入：作为封闭系统，注射的物质不会向全身扩散，具备极高的安全性，该试验已在严格审查所有安全性数据后获得了 FDA 的批准。罗根对此打趣调侃道：“天知道他们（FDA）可从来没搞砸过任何事。”谈到注入眼部的数万亿个病毒载体胶囊时，辛克莱透露，这套载体中装载了三组特定的基因——简称为“OSK”。这三组基因能够安全地重编程细胞，重启深藏于体内的人体“青春备份”。辛克莱甚至坦言，现在自己在街上看到步履蹒跚的老人时，眼里看到的不再是一个“衰老的人”，而是一个“需要被系统重启的人”。罗根忍不住大笑：“如果这真的是你看待人们的方式，那这份工作简直就是为你量身定制的。” ```mermaid flowchart TD accTitle: 细胞重编程与细胞状态对比 accDescr: 对比山中伸弥全能重编程与辛克莱OSK部分重编程在细胞身份与功能上的差异。 subgraph Yamanaka["山中伸弥方案 (OSKM 因子)"] Y1["成熟分化细胞"] -->|"4 个转录因子 (含 c-Myc)"| Y2["诱导性多能干细胞 (iPSC)"] Y2 -->|"细胞身份清零 / 丧失特化功能"| Y3["潜在肿瘤/畸胎瘤风险"] end subgraph Sinclair["辛克莱方案 (OSK 因子)"] S1["衰老细胞 (丢失表达记忆/充满表观遗传损伤)"] -->|"剔除 Myc 仅用 OSK"| S2["安全恢复 75%–80% 青春表征"] S2 -->|"保留细胞身份与特化功能"| S3["恢复 20 岁巅峰机能 / 组织再生"] end ``` 辛克莱借用老式黑胶唱片与光盘（CD）来形象化表观遗传学的损伤机制：生命最初构建年轻机体的 DNA 蓝图在年老时依然完好无损地存在于体内，衰老的过程并非硬件彻底损毁，而是唱片表面布满了划痕，导致机器无法正确读取曲目；而 OSK 的作用正是“抹去划痕”，让细胞重新读取原本的年轻指令。2006 年日本科学家山中伸弥（Shinya Yamanaka）因发现能将成体细胞诱导为多能干细胞的四种转录因子而荣获诺贝尔奖，但若将人体器官细胞完全逆转为没有任何分化特性的干细胞，不仅可能迅速致死，还会诱发癌症。辛克莱团队剔除了可能致癌的 Myc 基因，只保留 OSK，使细胞能够安全回到约 75% 至 80% 的年轻状态，既不会彻底清空细胞特异身份，又能让老化的细胞重新找回 20 岁巅峰时期的工作机能。 ### [13:44](https://www.youtube.com/watch?v=hxid7FofhMw&t=824s) 从致盲眼疾到神经与关节再生：逆转物理损伤将该技术率先落地于眼部疾病，源于辛克莱实验室华人学者吕垣澄（Yuancheng Lu）在 2017 年的前瞻性建议。虽然辛克莱最初提议先从肝脏着手，但吕垣澄坚持以结构闭环的眼球作为突破口。仅在美国，青光眼就影响着约 4000 万人，黄斑变性的患病规模更为庞大，而实验室已成功逆转了小鼠的此类病症。面对罗根关于“物理创伤是否也能被重格式化修复”的提问，辛克莱表示这正是他们近年攻克的核心课题：无论是中枢神经、周围神经还是视神经受损，OSK 均展现出促使神经重新生长的能力，其研究成果更曾登上 2020 年《自然》（Nature）杂志的封面。中国的一个研究团队也将该技术引入关节损伤小鼠体内，成功再生出了肌肉与骨骼组织。 - 青光眼全美患病人群达 4000 万人，老年性黄斑变性患者群体更为庞大。 - 2020 年《自然》杂志封面论文展示了受损视神经在重编程因子的作用下实现再生与结构连接。 - 罗根分享了自己饱受困扰的左膝旧伤：此前切除了部分半月板并进行了前交叉韧带（ACL）重建，即便干细胞注射能带来少许缓解，软骨磨损仍无法逆转。 - 辛克莱确认该技术正拓展至背部损伤、关节创伤及骨关节炎等退行性与外伤性病变。 ### [16:19](https://www.youtube.com/watch?v=hxid7FofhMw&t=979s) 竞技超级士兵、口服长寿药与被阻断的跨国投资肢体与关节再生的前景让罗根联想到竞技体育的颠覆：未来很可能会诞生大批宛如“超级士兵”的职业运动员，人人都具备迈克尔·乔丹般从半场起跳暴扣的惊人身体素质。辛克莱对此表示赞同，甚至预测未来可能需要引入专门的 DNA 检测来筛查运动员是否植入了 OSK 基因。辛克莱更爆出猛料：其实验室的技术进展比外界所知的至少超前 8 年，目前他们正在测试一种可口服的饮剂与药丸，在小鼠实验中已成功实现了机体逆龄焕新。罗根兴奋地主张对于行将就木的八旬老人，应该绕过繁琐的 FDA 审批直接放开尝试：“对于一位行将离世的老人，如果这款药水可能致命，但也可能让你重回 30 岁，那还有什么好犹豫的？” 辛克莱透露自己因此类研究收到了海量求助邮件，甚至不得不将个人邮箱从公开网站上移除，曾有患者直接守在其办公大楼拒不离开。这项前沿生物技术的战略价值也引起了地缘政治的警觉：美国政府曾以担忧尖端技术外流导致敌方制造“超级士兵”为由，直接动用国家安全权力，叫停了一笔原本计划投向辛克莱旗下公司的 1.6 亿美元外国投资。当罗根试图追问具体是哪个国家并先后猜测中俄时，辛克莱避开了具体国名，仅含蓄透露“介于美国和中国之间”，并感叹那是一次代价极其沉重、令人痛心的遭遇。 ### [19:07](https://www.youtube.com/watch?v=hxid7FofhMw&t=1147s) 苏联人猿杂交实验的传闻与现代嵌合体研究乔·罗根（Joe Rogan）与大卫·辛克莱（David Sinclair）将话题引向了一段充满争议的科学历史：二战期间苏联试图制造“人猿杂交”（Human-Chimp Hybrid）超级士兵的秘密计划。罗根提到，苏联在二战中承受了极其惨烈的人员伤亡，阵亡士兵高达数千万人，因此苏方内部便萌生出一种念头——“如果上战场的不是人类该有多好？”于是他们试图将人类与黑猩猩结合，培育出一批不需要承受人类痛苦、体魄强健的类人猿超级战士。辛克莱对此附和并透露，纽约就有一位科学家以此为研究方向。辛克莱曾与其同台交流，那位科学家在实验室中成功制造出了人猿杂交嵌合体胚胎，不过并未让胚胎足月发育。罗根感叹道，如果在美国这样拥有严格法律、道德伦理规范以及 FDA 监管的环境下，科学家都已经在进行此类实验，那么在那些缺乏法律约束的国家和暗处，天知道正在发生着多么疯狂的事情。 ### [20:25](https://www.youtube.com/watch?v=hxid7FofhMw&t=1225s) 基因筛选、《千钧一发》与臭名昭著的生育诊所丑闻辛克莱指出，现实中人类的基因工程与胚胎筛选早就已经存在。在美国，只要父母有足够的财力，就可以在受孕或试管婴儿阶段进行性状筛选——不仅可以筛选健康指标，还可以选择长相、身高甚至智商，这完全就是经典科幻电影《千钧一发》（Gattaca）的现实翻版。罗根随后将话题延伸到相关的伦理失控案例：许多辅助生殖领域的荒诞丑闻。罗根提及多起生育医生瞒着患者、滥用自己精液给成百上千名女性受精的恶性事件，辛克莱也笑着提到自己孩子的伴侣之一，其生物学生父就是全美这类繁衍了数百个孩子的捐精者之一。罗根甚至查阅到，当年某些涉案医生还曾荒唐地宣称自己让一只红毛猩猩受了孕。现场随后查证了苏联生物学家伊利亚·伊万诺夫（Ilya Ivanov）在 1920 年代尝试杂交人类与猿猴的真实历史记载： - 坊间流传斯大林曾要求伊万诺夫创造一种“不知疼痛、耐力极强且对食物品质无所谓”的无敌新人类士兵，以此重建红军。 - 科学史学者基里尔·罗西亚诺夫（Kirill Rossiianov）在 2002 年发表于《Science in Context》的权威论文中梳理了伊万诺夫培育人猿杂交种的失败尝试，并将其作为科学伦理失控的重要警示。 - 历史调查证实，关于斯大林亲口下达该指示的名言并无确凿档案支撑，但这起荒诞的伦理丑闻本身揭示了当时利用人猿杂交服务于军事设想的疯狂狂热。 ### [22:45](https://www.youtube.com/watch?v=hxid7FofhMw&t=1365s) “实验室兽人”、未来战争与真正颠覆社会的性爱机器人罗根对这种超级士兵的概念提出了一个现实而残酷的道德思考：从战争的角度来看，如果人类真要打仗，究竟是派出人造的“兽人”替我们流血，还是让街坊邻居家那个单纯为了攒大学学费而参军的邻家男孩约翰尼·罗宾逊（Johnny Robinson）去战死沙场？辛克莱提醒道，普通黑猩猩的力气极大，一记重拳就能致人于死地，肉体力量远超常人认知。辛克莱随后将视角转向现实：人类当前正在加速制造人形机器人，未来被直接征召入伍的更有可能是这些机械战士；但这也带来新的隐患——一旦每家每户都普及了人形机器人，政府是否能在战时直接征用普通人家中的设备？然而罗根坚信，机器人技术未来面临的最直接、最巨大的社会问题其实是“性爱机器人”： - 对于没有性爱机器人、想找真实伴侣的人来说，现实中可能已经无人可选，因为多数人早已选择沉溺于没有复杂人际纠葛的机器伴侣中。 - 机器伴侣与当前 AI 的最大共性在于极端谄媚。AI 只会不断对你说：“大卫，你太棒了，你做的每件事都无可挑剔。” - 真实的夫妻与人际关系之所以珍贵，恰恰在于伴侣会毫不留情地指出你的自私与讨厌之处，迫使你反思并获得心智成长；而面对 AI，“就算你整天对着它的脸放屁，它也会夸奖你的屁放得真香”。 ```mermaid flowchart TD accTitle: AI谄媚与真实人际关系的对比 accDescr: 对比AI机器人提供的无条件逢迎与真实人类关系中带来的磨合成长。 subgraph AI["AI 与性爱机器人模式"] A1["绝对顺从与奉承"] --> A2["缺乏真实摩擦与反馈"] A2 --> A3["陷入自恋孤立，心智停止成长"] end subgraph Human["真实人际关系模式"] H1["指出缺点与自私行为"] --> H2["直面矛盾，反思与沟通"] H2 --> H3["互相磨合，促成心智与人格成熟"] end ``` ### [25:19](https://www.youtube.com/watch?v=hxid7FofhMw&t=1519s) 超级智能的日常荒谬与 AI 在数学上的突飞猛进辛克莱指出，未来的家用机器人将会比整个人类文明的所有智慧总和还要聪明。罗根打趣地描绘了一幅荒谬的日常生活图景：人类一边吩咐一个智力超越爱因斯坦与所有诺贝尔奖得主集合体的超级机器人去“把洗碗机里的盘子码好”，一边顺便要求它在刷碗的间隙用通俗语言解释一下量子纠缠；而机器人则可能一边漫不经心地洗着盘子，一边随手顺便把困扰人类千百年的衰老难题给彻底攻克了。罗根提到，AI 在纯数学领域的推理进展已经令人瞠目结舌——仅在最近的数周之内，AI 就连续攻克了数学界几十年来悬而未决的 50 多道复杂数学方程，解题速度犹如信手拈来。 ### [26:14](https://www.youtube.com/watch?v=hxid7FofhMw&t=1574s) 两个月跑完160年：AI 颠覆长寿药物研发范式辛克莱指出，尽管生物系统的复杂程度远超纯数学，但 AI 已经接管了他哈佛实验室里原本由大量研究人员承担的繁杂科研工作。辛克莱透露了一项惊人进展：他的实验室刚刚利用 AI 在短短两个月内完成的计算与筛选工作，如果放在过去用传统生物学方法，需要足足消耗 160 年的时间。面对罗根对其延寿药物鸡尾酒的追问，辛克莱坦承自己目前还没有亲自服用该复合配方。虽然团队进行了大量安全性测试且结果极佳，但由于全世界的目光都在紧盯着他的一举一动，他必须严格遵守法律法规和临床审批程序，绝不能在公开场合做出任何违规之举，“一旦临床试验出现任何差池，后果不堪设想”。辛克莱详细阐述了这“两月顶160年”的技术突破内幕： - **研发目标**：以往他们逆转衰老依靠的是多成分混合的分子鸡尾酒，但团队的目标是找到“单一分子”，使其能够同时兼具细胞内的 3 到 4 种不同活性来代替整个鸡尾酒配方。 - **制药行业瓶颈**：传统大型跨国药企耗费数亿美元甚至数十亿美元，通常也只能研发出针对单一靶点活性的分子。让一个仅有约 20 人的学术实验室去合成能够一举实现多靶点活性的单药，在五年前的制药技术条件下几乎是天方夜谭，耗费数千年都未必能成。 - **AI 与海量筛选**：辛克莱团队与圣裘德儿童研究医院（St. Jude Children's Research Hospital）的小组展开深度合作，借助尖端 AI 计算平台，他们已经能够将筛选通量从最初的 100 亿个候选结构提升到当下能够同时对高达 1 万亿个理论分子及已知药物进行空间结构与活性的虚拟模拟计算。 ### [28:27](https://www.youtube.com/watch?v=hxid7FofhMw&t=1707s) 从万亿分子到两百个候选药物：AI 与计算生物学的筛选革命在闲聊播客录制技巧并提及重新启动的《Lifespan》播客后，戴维·辛克莱尔（David Sinclair）将话题带回了抗衰老药物筛选的巨大“分子漏斗”。在实验初期，候选库中包含多达 1 万亿个分子，科学家的终极目标是将其缩减为唯一的最优药物分子。如果在传统的湿实验台（wet bench）上逐一测试这 1 万亿个分子，哪怕动用自动化机器人和成群的研究生，也需要花费成百上千甚至上万年的时间。如今这一过程完全被搬到了计算机中。得益于 Google DeepMind（AlphaFold 技术）解决了人体全部 2 万种蛋白质的三维结构难题，研究团队利用庞大的算力，模拟这 1 万亿个分子与靶标酶之间的分子对接（docking）。经过数月的超级计算模拟，筛选漏斗的末端最终只留下大约 200 个高潜力的候选分子。辛克莱尔透露，他的实验室正在将这 200 个分子直接用于人类细胞实验，并且全程配备 AI 视觉系统——通过 AI 图像识别分析，仅凭显微观察就能判断人类细胞是否从 92 岁的高龄状态成功逆转回 20 岁的年轻状态。 ```mermaid flowchart TD accTitle: 计算生物学抗衰老药物筛选流程 accDescr: 展示从上万亿虚拟分子经过AI对接与实验测试最终筛选出逆龄药物的漏斗流程 subgraph Computational ["阶段一：虚拟高通量计算"] A["1 万亿个候选分子"] --> B["DeepMind 蛋白质组结构库 (20,000 种人类蛋白质)"] B --> C["超级算力分子对接模拟 (耗时数月)"] end subgraph WetLab ["阶段二：实验室生物验证"] C --> D["精选出的 200 个候选分子"] D --> E["人类细胞体外测试"] E --> F["AI 图像视觉监控 (评估细胞是否从 92 岁逆转回 20 岁)"] end ``` --- ### [29:38](https://www.youtube.com/watch?v=hxid7FofhMw&t=1778s) 细胞返老还童的“刹车”机制与 OSK 鸡尾酒乔·罗根（Joe Rogan）半开玩笑地提出了一个担忧：这种逆龄技术会不会矫枉过正，把人一路倒退变成婴儿？他坦言自己可不想重当婴儿，“停在 25 岁就很完美”。辛克莱尔笑称自己在公开场合聊这个经常会被网络喷子攻击，因为人们总喜欢断章取义截取片段，宣称“辛克莱尔说我们所有人都能变回 20 岁”。但他强调，这确实是他们在实验室里真真切切做到的事情：取下 92 岁老人的皮肤细胞，逆龄过程会在 20 多岁时稳稳停住，不会无限倒退。辛克莱尔解释，在体外细胞中逆转衰老并不深奥，“如果你的车库里有 OSK 基因，你也能做这个实验”。过去十年里真正的科学攻坚难题，是如何安全地将其转化为可在人体内递送的临床药物，以及如何精准控制这套逆龄“刹车”机制。山中伸弥教授最初发现的四种多能干细胞重编程因子（Yamanaka factors: Oct4, Sox2, Klf4, c-Myc）极易引发畸胎瘤。辛克莱尔的学生在实验室里尝试了无数种胚胎期基因组合（因为受精卵和早期胚胎必须在生命的第一周重置生物年龄，否则新生儿就会继承父母的真实年龄），历经反复失败后终于发现，剔除致癌的第四个因子，仅保留三种基因（OSK），就能安全触发细胞重置并精确停留在年轻成熟期。 - **OSK 因子**：去除了原山中因子中高致癌风险的 c-Myc，保留了安全逆转细胞表观遗传年龄的能力。 - **胚胎重置启示**：胚胎在着床前后有一套天然的生物年龄重置程序，实验室正是借鉴了这一自然演化出的抗衰机制。 --- ### [31:13](https://www.youtube.com/watch?v=hxid7FofhMw&t=1873s) 表观遗传时钟与“一夜变老”的阴暗面当被问及如何精准测定细胞变年轻时，罗根猜测是否是通过端粒（telomeres）长度来衡量。辛克莱尔指出，端粒虽然也是指标之一，但目前公认最精确的分子标尺是 DNA 甲基化（DNA methylation）。甲基基团结构极其简单，仅为一个碳原子连接三个氢原子（$-CH_3$），细胞在胚胎发育期间正是利用这些甲基作为分子标签来关闭特定基因——比如立志成为神经元的细胞会甲基化并关闭肝脏或皮肤基因，未被甲基化的基因则终生保持开启，以此维持细胞身份与健康。然而随着岁月流逝与外界损伤（如紫外线暴晒、DNA 双链断裂等），这些甲基化标记会发生规律性的漂移与错乱。辛克莱尔的好友史蒂夫·霍瓦特（Steve Horvath）据此发明了“霍瓦特表观遗传时钟”（Horvath Clock）。通过读取甲基化图谱，不仅能测出细胞或个体的生物学真实年龄，还能人为干预。辛克莱尔的实验室在 2023 年发表的研究中，就成功利用诱导 DNA 损伤使小鼠迅速衰老。这让罗根脑洞大开地联想到间谍阴谋：“如果有敌国特工或俄罗斯间谍在你的咖啡里下毒，岂不是能让你一夜之间变成 99 岁的老翁？”辛克莱尔坦言从技术原理上说，科学界确实已经掌握了快速衰老的机制，罗根随即打趣称愤怒的妻子也能用这招给丈夫下药。 --- ### [32:50](https://www.youtube.com/watch?v=hxid7FofhMw&t=1970s) 当外表不再揭示年龄：伦理玩笑与社会观念冲击谈话转向了逆龄技术可能带来的社会文化冲击。辛克莱尔提到网上的一则争议话题：“如果一个 92 岁的老人外表重返 25 岁，你会愿意和他/她发生关系吗？”辛克莱尔风趣地回应道：“当然愿意，想象一下他们脑子里该积攒了多少人生智慧！”罗根则犀利反问：“问题是，那个看起来 25 岁但活了 92 岁的人，看得上你吗？他们可能也只想找另一个 20 岁外貌的人。” 两人调侃起当下社会对“年轻女孩嫁给年迈富豪”的复杂心理。目前老男人吸引年轻伴侣主要靠银行存款，旁人往往投以异样甚至反感的目光；但如果未来通过生物技术让一位 99 岁的亿万富翁不仅富有，外表也完全是健康的 20 岁青年，社会的道德评判与反感是否会转化为“他在利用百年的信息差和阅历进行猎艳”的全新伦理焦虑？辛克莱尔断言，这一天终将到来——未来肉眼将彻底无法判断一个人的真实年龄，必须通过分子基因检测才能验明正身。届时人们可能不再隐瞒年龄，反而会自豪地虚报更大的岁数，以彰显自己的寿命资历。 --- ### [34:10](https://www.youtube.com/watch?v=hxid7FofhMw&t=2050s) 苏美尔王表、史前超前文明与长生不老的古代猜想罗根将话题引向了历史与另类考古学（Alternative Archaeology）领域的未解之谜，特别是美索不达米亚的古代苏美尔文明。罗根阐述了在非传统考古圈流传甚广的假说：人类文明的发展或许并非从洞穴原始人到现代工业社会的线性上升过程，在几万年前可能存在过高度发达的前代文明，但遭遇彗星撞击等全球大灾难（如新仙女木期事件）后被彻底抹去，现代文明只是一次废墟上的重建。这种假说经常被用来解释那些难以逾越的巨石建筑奇迹，例如吉萨大金字塔内部精密的工程结构、秘鲁马丘比丘和萨克塞瓦曼（Sacsayhuamán）那严丝合缝的巨石墙，以及黎巴嫩巴勒贝克（Baalbek）重达数百吨、被抬升至离地 9 米高空的超巨型三石塔（Trilithon stones）。罗根特别指出了古苏美尔王表（Sumerian King List）中的诡异记录： - **大洪水前**：统治者的在位时间长达数万年或数千年（神话般的极长寿命）。 - **大洪水后**：诸王的统治年限断崖式暴跌，从几百年迅速过渡到三五十年的人类正常水平。罗根推测：既然古代工匠能将数百吨的巨石从数百英里外运来并精准拼装，证明其工程学造诣远超后人想象；那么在生命科学领域，史前文明是否也曾掌握过某种基因工程或极端延寿技术？古代文献记载的长寿君王，难道真的仅仅是夸张的神话与记录错漏，抑或是某种失落的高科技产物？ --- ### [37:06](https://www.youtube.com/watch?v=hxid7FofhMw&t=2226s) 57岁的逆龄状态与拥有500年科研寿命的潜力面对罗根的大胆猜想，话题落回到了辛克莱尔自身的身体状态上。辛克莱尔即将在数周后迎来 57 岁生日，罗根当面赞叹他的外貌保持得极其惊人，不仅皮肤紧致，满头黑发也没有染发或植发的痕迹。辛克莱尔打趣说，人们总怀疑他的头发是假的，但他显年轻的秘密之一其实是因为常年泡在地下实验室里科研，几乎晒不到紫外线，从而极大地减少了日光造成的表观遗传光老化损伤。赞叹之余，罗根提出了一个更为深远的议题：知识和智慧的指数级复利。辛克莱尔在短短 50 多年的人生里就已经在遗传学领域做出了划时代的突破；倘若人类真的攻克了衰老，让顶尖科学家不再因身体机能退化和死亡而被迫中断事业，而是拥有 500 年甚至 1000 年健康的巅峰科研寿命，持续不断地学习与积累，人类社会的科技进步、认知深度与创新爆发力将会以何种不可思议的指数级速度向前推进。 ### [38:11](https://www.youtube.com/watch?v=hxid7FofhMw&t=2291s) 寿命延长的未来图景与现代老龄认知的转变当谈及古代文明是否存在过高度发达的科技或超长寿命时，戴维·辛克莱尔（David Sinclair）调侃自己作为一名哈佛科学家，绝不会在缺乏实证的情况下胡乱断言，但乔·罗根（Joe Rogan）提出的核心议题十分深刻：人类看待远古文明与恐龙的方式往往存在偏差，对未来的预判也是如此。圣经和古文明记载中那些活到数百岁的传说，引出了一个至关重要的人文命题——如果人类寿命真的被大幅延长，活到100岁时依然处于生理黄金期，人生的底层逻辑将被彻底重塑。届时，人们的婚姻观念、职业规划都将发生翻天覆地的变化，一个人在一生中完全可以经历“多段不同的人生”、多段婚姻并组建多个家庭。辛克莱尔断言，这早已不是“能否实现”的问题，而是“何时实现”的必然，正如莱特兄弟制造出滑翔机之后，人类注定会造出协和超音速客机、迈向太空一样。这种生命周期的跃迁已经在近代拉开了序幕。罗根指出，如今57岁的人与1930年代的57岁老人相比，其体能、健康状态存在着天壤之别。放在近一个世纪前，年近六旬的人早已垂垂老矣、行将就木；而罗根表示自己再过一周就满59岁了，童年时他总觉得59岁的人步履蹒跚、毫无生机、只等着退休等死，可现在的自己依然精力极其充沛。这种巨变背后是现代生活认知的升级：过去的人根本不知道什么是合理的营养素与维生素摄入，对抗阻力量训练、睡眠质量乃至红光疗法（Red light therapy）一无所知，反而充斥着酗酒、重度吸烟、熬夜以及接触杀虫剂等大量有害行为。 - **寿命延长的社会影响**：未来百岁若处于生理盛年，人生将衍生出多元轨迹，包括多重职业阶段与多次家庭重组。 - **莱特兄弟隐喻**：基础抗衰老机制已经证实（滑翔机阶段），后续必然向更高级的全面逆龄技术（协和客机/太空探索）演进。 - **时代生理差距**：现代50多岁人群的健康状态远优于1930年代同龄人，得益于营养学、睡眠管理、力量训练及健康生活方式的普及。 --- ### [40:05](https://www.youtube.com/watch?v=hxid7FofhMw&t=2405s) “冻龄”神话与逆转衰老的科学愿景在讨论身体状态的过程中，制作人杰米（Jamie）在屏幕上调出了一名在社交网络上引发轰动的新加坡男性照片（陈传多 / Chuando Tan）。屏幕上那张看似只有28岁至30岁出头的面孔，实际年龄竟已近60岁。罗根直呼这简直不可思议，甚至一度怀疑该账号是由AI生成的钓鱼虚构账号，或是照片经过了深度修图。但检索显示，这位新加坡摄影师早在AI广泛普及之前的2024年就已爆火，如果是伪造早就会被彻底揭穿。大家感叹，这或许是极端罕见的基因天赋，就像综合格斗选手约埃尔·罗梅罗（Yoel Romero）那样的体能怪兽；相比之下，某些肤色苍白、皮肤菲薄的人群在衰老过程中则显得极为残酷。辛克莱尔指出，社交媒体上充斥着严重的躯体变形障碍（Body dysmorphia），许多健美运动员明明肌肉发达却自感弱小，也有很多人对自己的容貌衰老产生了病态的认知扭曲，进而推动了洛杉矶等地极其庞大的医美整形产业。然而，医美不过是表面功夫。辛克莱尔团队所追求的愿景完全不同：未来人们或许只需找医生开一种药片，甚至只是一管面霜涂抹在脸上，就能从细胞层面“真正变年轻”。这一愿景绝非空中楼阁，因为哈佛实验室已经在小鼠身上实现了这种逆转，将其转化到人类身上只是时间问题。 --- ### [41:45](https://www.youtube.com/watch?v=hxid7FofhMw&t=2505s) 绝密“返老还童饮剂”：四周逆转小鼠生理与早衰辛克莱尔在节目中首次公开了实验室的重磅最新进展。针对小鼠无法咀嚼药片的情况，他的团队研发出了一种口服药饮（Cocktail drink）。该配方包含三种核心成分，目前在其实验室内部被列为“最高机密”（Top secret），所有研究人员均签署了严格的保密协议。他们给老年小鼠按照“每周给药三天（周一、三、五给药，周末停药）”的节奏连续灌服，仅仅过了四周，小鼠在生理机能和心理认知测试中的表现就发生了惊人的蜕变。这项实验原本仅打算进行一个月（因为恰逢圣诞假期，实验被迫中断），但结果却令研究团队大为震惊。以往利用基因疗法恢复小鼠视力通常需要六到八周，而这款化合物口服饮剂仅用四个星期，就让普通老年小鼠变得更加强健敏捷，笼内活动量与记忆力显著提升。此外，辛克莱尔团队还在早衰症（Progeria）小鼠模型上进行测试——这些小鼠携带早衰基因突变，身体老化速度极快——实验表明该疗法同样在逆转它们的早衰表征。 ```mermaid flowchart TD accTitle: 口服抗衰配方与表观遗传重置机制 accDescr: 展示哈佛实验室从口服给药到激活TET酶、清除DNA甲基化，最终实现机体逆龄的通路。 subgraph Administration ["给药方案"] A["三元核心配方口服饮剂 (Top-secret 3-component cocktail)"] B["给药周期: 每周3天 (周一/三/五给药，持续4周)"] A --> B end subgraph EpigeneticReset ["表观遗传重编程机制"] C["依赖 TET 家族酶 (TET1, TET2, TET3)"] D["精准清除 DNA 上的异常甲基化标记 (Demethylation of DNA)"] E["重置表观遗传生物时钟 (Resetting the Biological Clock)"] B --> C C --> D D --> E end subgraph PhysiologicalOutcomes ["生理逆龄表型"] F["体能与肌肉力量大幅恢复"] G["脑部认知与迷宫记忆力提升"] H["早衰症模型恶化进程逆转"] E --> F E --> G E --> H end ``` --- ### [44:46](https://www.youtube.com/watch?v=hxid7FofhMw&t=2686s) TET酶与重拨生命时钟：逆转认知衰退与伤口自愈谈及这种口服饮剂的作用原理时，辛克莱尔解释，它并非仅仅为细胞提供单纯的营养或改善代谢环境，而是通过表观遗传重编程实现了“系统重启”与“底层软件重装”。其核心驱动力依赖于人体内的一类关键基因——TET基因家族（TET1、TET2、TET3）。TET基因编码的酶专门负责移除DNA链上的甲基化标记（Methyls）。DNA上的甲基化修饰就像是记录生命流逝的“时钟刻度”，而辛克莱尔团队证实，只要敲除或阻断TET基因，无论是视力恢复疗法还是口服饮剂都会彻底失效。这一发现的核心价值在于：生命时钟不仅仅是记录时间的指针，当你人为地把这个时钟的指针向后拨动时，机体的生理时间也会跟着发生逆转——“生物钟本身就是衰老，衰老就是这堵生物钟”。辛克莱尔团队此前正是凭借这一颠覆性发现登上了《自然》（Nature）杂志的封面。 ``` ┌────────────────────────┐ │ 衰老累积过程 │ │ DNA 甲基化标记异常累积 │ │ (表观遗传时钟走快) │ └───────────┬────────────┘ │ TET 酶激活 (TET1 / TET2 / TET3) ───────────────┴─────────────── │ ┌───────────▼────────────┐ │ 逆向重编程机制 │ │ 清除甲基基团，重置生物钟 │ │ (将表观遗传时钟拨慢) │ └───────────┬────────────┘ │ ┌───────────────────────┴───────────────────────┐ ▼ ▼ ┌───────────────────────────┐ ┌───────────────────────────┐ │ 大脑认知重获新生 │ │ 组织自愈机能复苏 │ │ • 学习记忆力显著提升 │ │ • 皮肤外用促进创口快速愈合│ │ • 找回遗忘记忆(阿尔茨海默)│ │ • 重现孩童般高强度修复力 │ └───────────────────────────┘ └───────────────────────────┘ ``` 这种机制对大脑认知具有重大的医学意义。辛克莱尔确认，多个独立实验室与他们自己的数据均表明，逆转小鼠大脑年龄能显著改善其学习认知能力；更令人兴奋的是，即将发表的研究显示，小鼠那些原本被认为已经丢失的记忆竟能够被重新唤回。辛克莱尔据此推论，阿尔茨海默病患者的大脑记忆并未真正消失，只是神经系统丧失了访问和检索这些记忆的通路。年轻的身体之所以不得阿尔茨海默病，是因为年轻细胞拥有强大的自我修复机制；只要让全身重返年轻，机体就能自行攻克当前被视为不治之症的各类退行性疾病。罗根对此深有共鸣。他以养育三个孩子的经验提到，孩童的伤口愈合速度令人惊叹——孩子头上磕出深色伤痕或皮肤划伤，几天之内就能彻底消失，而同样的外伤留在中年人身上可能需要整整四个月才能代谢平复。辛克莱尔随即透露，当他们将这套抗衰修复配方制成外用药剂涂抹在老年小鼠皮肤上时，小鼠的创口愈合速度瞬间恢复到了幼年状态，这预示着该技术在未来的外伤修复与器官再生领域拥有极其广阔的应用前景。 - **TET酶的关键机制**：TET1、TET2、TET3通过DNA去甲基化重置表观遗传时钟，是启动逆龄恢复的必要开关。 - **阿尔茨海默病的新视角**：记忆并非不可逆地彻底丢失，而是“读取通路受阻”，通过脑细胞逆龄有望唤醒休眠记忆。 - **外用自愈潜力**：配方局部涂抹不仅停留在外观年轻化，还能从细胞修复层面赋予组织如同幼童般迅速愈合的能力。 ### [47:37](https://www.youtube.com/watch?v=hxid7FofhMw&t=2857s) 在小鼠身上培养人类毛发与实验室植发前景两人的对话从面部抗衰老美容应用转向了头发再生领域。David Sinclair 透露，他的实验室目前已经在小鼠身上成功长出了真正的人类头发。这一突破花费了数年时间，目的是测试团队是否能够让人类毛囊重新生长并恢复年轻时的深色发色。Sinclair 笑着提到，他曾把这项研究成果发布在 Instagram 上，结果哈佛大学官方立刻勒令他：“赶紧把那个删掉”，但这项技术是切切实实存在的。其实验室利用人类干细胞培育出微小的毛发球团，耗时数月使其生长，随后将这些小球切开铺平成一片平整的人类皮肤，再移植到免疫系统经过改造、能够接纳人类皮肤的实验小鼠背上。最终，小鼠背上便长出了一丛丛乌黑浓密的人类毛发。 Joe Rogan 随即开玩笑地问，既然能人工培育毛发，那能不能搞出像 Colin Kaepernick 那样夸张的复古爆炸头（Afro），纯粹用来恶搞和惹恼别人。Sinclair 笑着回应道：“我们可以做到”，并指出他们的实验室是全球少数掌握这项人造毛发技术的团队之一。Sinclair 曾考虑围绕这项技术创立一家公司，但他也坦言目前的毛发移植手术可能还是更直接省事。这引发了 Rogan 对传统植发弊端的吐槽：Rogan 曾做过植发手术，他将此形象地比喻为“把一群身体极度健康的人硬生生搬到一个所有人都在死去的衰退小镇”——医生把后脑勺那些寿命持久的坚韧毛囊挖出来，移栽到头顶那片原本就在持续脱落的荒地里。虽然后脑勺移过去的头发确实能成活，但原本周边的天然头发却依然在不可逆转地枯萎，加上后枕部的供体资源极其有限，导致许多做过植发的男士发型极其滑稽怪异：前额是一条死板僵硬的发际线，后面却稀稀拉拉、混乱不堪。 - **小鼠培养人类毛发机制**：提取人类干细胞培养成微型毛发组织球，耗时数月形成结构后展开为人类皮肤皮瓣，缝合移植到免疫缺陷小鼠背部形成可生长的人类黑色毛囊。 - **植发手术的生理局限**：后枕部可采集毛囊数量存在绝对上限；移植后无法逆转周围原有脆弱毛囊的微小化与脱落。 --- ### [49:18](https://www.youtube.com/watch?v=hxid7FofhMw&t=2958s) 他达拉非与西地那非：从脱发、心血管到癌症抑制的多重机制谈及自身如何保养头发时，Sinclair 抛出了一个让 Rogan 颇感意外的日常用药：微剂量的他达拉非（Tadalafil，即西力士的有效成分，每天低剂量服用 7 毫克）。Rogan 笑称许多人肯定会调侃这是在给自己找借口，但他也认可该药的多种生理效益，并指出不少运动员为了提升耐力表现也会偷偷使用。Sinclair 强调，最新的肿瘤学研究揭示了勃起功能障碍（ED）类药物出人意料的抗癌潜能，他甚至在社交媒体上发文感慨“这药简直完美，谁能不爱呢”。最新出炉的研究显示，在小鼠模型以及临床回顾性队列中，服用这类药物的个体对头颈癌等多种恶性肿瘤展现出了显著的抗性。 Rogan 猜测这是否仅仅是因为血液循环得到改善，Sinclair 澄清说，除了药物通过一氧化氮（Nitric Oxide）信号通路舒张全身血管的基本药理外，抗癌效果主要归功于两项全新发现的细胞机制。第一项机制涉及免疫微环境：他达拉非能够有效瓦解并抑制髓系来源抑制性细胞（MDSCs，即保护肿瘤免受宿主免疫系统反击的“护盾”细胞），从而让肿瘤重新暴露在机体免疫监视之下，导致小鼠和患者体内的实体瘤出现明显萎缩。第二项机制则是基于西地那非（Sildenafil，万艾可原研成分）的发现：许多癌细胞除了疯狂吞噬葡萄糖（因此生酮饮食与断食有助于抗癌）之外，高度依赖宿主的胆固醇来进行恶性增殖，而西地那非恰好能切断并阻断癌细胞利用胆固醇的代谢通道。 ```mermaid flowchart TD accTitle: PDE5抑制剂的多重生理效应 accDescr: 展示他达拉非与西地那非在头发生长、心血管舒张及肿瘤抑制等方面的生物学机制。 subgraph PDE5["PDE-5 抑制剂 (他达拉非 / 西地那非)"] direction TB NO["激活一氧化氮 (Nitric Oxide) 通路"] IMM["阻断 MDSC 免疫抑制细胞"] MET["阻断癌细胞利用胆固醇"] end subgraph Effects["下游生理与治疗响应"] direction TB Vasodilation["血管扩张与微循环增强"] HairGrow["毛囊血液滋养 -> 促进头发生长"] TumorKill["肿瘤暴露于免疫系统 -> 实体瘤萎缩"] StarveCancer["阻断能量供给 -> 抑制头颈癌等肿瘤"] end NO --> Vasodilation Vasodilation --> HairGrow IMM --> TumorKill MET --> StarveCancer ``` Sinclair 随后回顾了万艾可最初研发时的著名逸事：辉瑞原本是将其作为治疗心绞痛和心血管疾病的降压药进行研发，结果临床试验结束后，受试患者（尤其是男性甚至包括其伴侣）坚决拒绝将剩余药丸交还给研究团队。临床数据表明，药物组有约 75% 的患者报告勃起功能显著增强，而安慰剂组仅为 22%，这项阴差阳错的副反应最终彻底改写了医药历史。针对头发健康的原理，Sinclair 解释毛囊萎缩脱落的关键诱因之一就是真皮乳头微循环血液供应不足，因此无论是外用米诺地尔（Minoxidil）还是全身性口服低剂量他达拉非，改善局部血流都能有效延缓脱发。 - **低剂量他达拉非方案**：Sinclair 每日维持摄入 7 毫克，用于微循环维持、防脱发与前列腺增生防护。 - **抗癌新靶点 MDSCs**：髓系来源抑制细胞原本充当肿瘤免疫豁免屏障，PDE5 抑制剂可抑制其活性。 - **肿瘤胆固醇依赖**：西地那非被证实能够遏制癌细胞对胆固醇的摄取与利用通路。 --- ### [52:08](https://www.youtube.com/watch?v=hxid7FofhMw&t=3128s) 药物个体化反应：双氢睾酮抑制剂的心理风险与眼部基因治疗临床试验针对雄激素性脱发的治疗方案，Rogan 提到了口服双氢睾酮（DHT）抑制剂（如度他雄胺/非那雄胺）。他分享了身边朋友的恐怖经历：对方在服药期间陷入极其严重的重度抑郁，甚至产生了自杀倾向，整个人处于精神崩溃的边缘；然而其本人浑然不知这是药物副作用，直到停药后所有抑郁症状彻底烟消云散，朋友才惊恐地意识到是 DHT 抑制剂直接扰乱了大脑神经机能。Sinclair 对此表示赞同，虽然他自己为了保护头发和预防前列腺肥大也在服用这类药物且未遭遇明显心理副作用，但他极其严肃地提醒受众：任何声称某种药物绝对“好”或“坏”的断言都是危险的，个体生物学差异极其巨大，所有处方药必须在专业医师严密监控下进行个性化评估与试用。 Rogan 借此将话题引向深层安全关切：既然个体差异如此剧烈，Sinclair 团队正在开发的重编程逆转衰老药物又该如何向全人类普惠推广？Sinclair 解释，任何正式推向大众的抗衰老疗法都必须经历极其严苛且多人群覆盖的临床试验阶段。他首度证实，目前团队已经展开了正式的人体临床试验，首批受试患者的眼睛内已经注射了导入的山中因子相关逆转衰老基因。当 Rogan 迫不及待地追问临床疗效到底如何、能不能“眨两下眼睛暗示一下”时，Sinclair 保持了严谨的监管底线，谨慎地表示目前因试验保密条例无法透露细节，但可以用允许公开的合规措辞告知大众：“一切都在按计划推进，目前没有任何负面不良事件需要汇报（Nothing bad to report）”。 - **DHT 抑制剂的神经精神副作用**：度他雄胺/非那雄胺等 5α-还原酶抑制剂阻断神经甾体合成，部分患者可能诱发严重抑郁、认知迷雾和自杀观念。 - **眼部逆衰基因人体临床进展**：首批人类患者已接受眼内基因递送，目前主要针对青光眼等视神经退行性病变，处于早期安全性与疗效追踪期。 --- ### [54:38](https://www.youtube.com/watch?v=hxid7FofhMw&t=3278s) GLP-1 药物的阴暗面：前部缺血性视神经病变（NAION）与眼中风警讯谈到针对眼部的适应症开发，Sinclair 指出除了青光眼，临床试验的另一核心目标是治疗突发性失明——非动脉炎性前部缺血性视神经病变（NAION）。令人震惊的是，Sinclair 披露这项疾病在近期发病率近乎翻倍，而背后的罪魁祸首直指当前红极一时的 GLP-1 受体激动剂类减肥降糖神药（如 Ozempic、Wegovy）。Sinclair 直言，虽然制药巨头出于商业利益极力回避这一话题，但 NAION 本质上就是眼部供血视神经发生的“眼内中风”，往往导致单眼发生无痛性突发视力丧失，且另一只眼睛随后极易发生连锁病变，现代医学对此几乎无计可施。哈佛大学著名眼科学家 Joseph Rizzo 领导的研究团队已在全球多中心队列中复现并验证了这一关联。 ```mermaid flowchart LR accTitle: GLP-1药物与眼中风风险链条 accDescr: 说明GLP-1药物引发NAION视神经病变的过程及流行病学调查发现。 GLP1["长期使用 GLP-1 类药物 (司美格鲁肽等)"] --> EyeCirculation["视神经局部灌注异常 / 微血管缺血"] EyeCirculation --> NAION["前部缺血性视神经病变 (NAION / 眼中风)"] NAION --> VisionLoss["突发性单眼视力永久受损 (继发另一眼失明风险)"] ``` Rogan 对此感到极度愤怒与震惊。他痛斥互联网上充斥着无数网红播客与带货领袖，毫无保留地鼓吹“所有人都可以且应当立即注射 GLP-1”，将其捧为改变人类社会的灵丹妙药，却丝毫不提刚刚暴露出的长期神经血管风险。两人在现场调取了最新的医学文献摘要：研究指出，使用司美格鲁肽等 GLP-1 药物的肥胖人群发生 NAION 的风险是非用药人群的 7.6 倍，而在糖尿病患者人群中风险更是飙升到了原来的 4 倍以上（此前部分早期研究甚至估算高危倍率极高）。尽管其在总人群中的绝对发生率仍属于罕见不良反应范畴（每万人中仅有少数个案），但鉴于全球数千万人正在大规模常规注射，这一比例代表着大量原本健康的个体正在不可逆地陷入失明深渊。Rogan 指出，许多疯狂站台的意见领袖背后都夹杂着隐秘的商业利益与药企持股，在大规模长期安全性尚未完全经受时间检验前，盲目造神是极其危险的。 - **NAION（眼部中风）病理机制**：睫状后短动脉血流灌注中断导致视神经乳头缺血、水肿并发生不可逆神经元坏死。 - **哈佛 Joseph Rizzo 团队研究**：流行病学数据显示，使用司美格鲁肽治疗肥胖症的患者被诊断为 NAION 的风险相较于未用药者高出数倍以上。 - **公共健康预警**：服用 GLP-1 类药物期间若出现任何单眼突发性无痛视野缺失，必须立即寻求急诊眼科神经病学评估。 ### [57:22](https://www.youtube.com/watch?v=hxid7FofhMw&t=3442s) GLP-1 药物的突破与“正向势头”的心理重塑大卫·辛克莱尔（David Sinclair）指出，虽然围绕降糖与减重药存在商业利益的讨论，但不可否认的是，GLP-1 受体激动剂类药物已经在全球范围内挽救了数以百万计的生命。目前约有 10% 的人尝试过这类药物，另有 25% 的人跃跃欲试。乔·罗根（Joe Rogan）表示赞同，虽然他的一位好友因严重不良反应不幸住院，但他也亲眼目睹该药物彻底改变了许多人的生活。特别是对那些受深层生理机制驱动、深陷严重食物成瘾而无法自拔的人来说，GLP-1 提供了摆脱失控食欲的契机。罗根强调，人们常常把成功完全归功于“自律”，自律固然是核心引擎，但在生活方式的转变中，“势头（Momentum）”的作用同样不可估量。当一个人通过药物或训练初见成效、减掉体重并感到身体状态好转时，这种正向反馈会产生巨大的前行动力。辛克莱尔随即分享了自己的切身经历：过去他受限于薄弱的意志力，连一整天的断食都很难坚持，尤其深受深夜吃零食的习惯困扰。在尝试了 GLP-1 受体激动剂后，他轻而易举地克服了饥饿感。更关键的是，在停药之后，由于在心理上突破了界限、形成了正向势头，他几个月前甚至顺利完成了长达两周的断食。 - 据辛克莱尔估计，大约 10% 的人群已尝试过 GLP-1 药物，25% 的人有尝试意向。 - 罗根的核心观点：“大家都喜欢谈自律，我认为自律确实是主引擎，但在任何改变生活的计划中，正向势头（Momentum）具有无与伦比的力量。” - 辛克莱尔通过短期体验 GLP-1 克服了夜间进食冲动，随后在不依赖药物的情况下成功完成了两周禁食。 --- ### [59:27](https://www.youtube.com/watch?v=hxid7FofhMw&t=3567s) 生酮饮食、断食与分子级清理：伴侣介导的自噬（CMA）当罗根询问辛克莱尔是否依然坚持植物基饮食时，辛克莱尔表示大部分时间如此。罗根随后分享了自己从一位长跑运动员朋友那里听到的经验：进入断食的最佳前置路径是先让身体进入生酮状态（Ketosis）。罗根日常以纯肉食为主，搭配泡菜（Kimchi）、德国酸菜（Sauerkraut）等发酵蔬菜。他发现，只要远离披萨、意面等高碳水化合物，胰岛素敏感度保持稳定，就不会出现过去那种“必须立刻吃东西”的狂暴饥饿感，断食 24 小时变得轻而易举。辛克莱尔鼓励罗根尝试将断食延长至三天，因为三天断食所带来的身体益处更为深远。他解释道，深度的生酮状态不仅能让头脑和身体感觉良好，还会触发体内被称为“伴侣介导的自噬（Chaperone-Mediated Autophagy, 简称 CMA）”的深层清洁机制。他在纽约的朋友兼科学家安娜·玛丽亚·库尔沃（Ana Maria Cuervo）正是该领域的权威学者。这一过程会高效清理并降解体内老化病变的蛋白质，促进细胞内蛋白质的重建与更新，是极为核心的抗衰老生物学机制。 ```mermaid flowchart TD accTitle: 断食与自噬抗衰机制 accDescr: 展示生酮状态到伴侣介导自噬的细胞清理流程 subgraph MetabolicState ["代谢转化"] A["减少碳水摄入 / 延长断食"] --> B["耗尽糖原储备"] B --> C["机体进入深度生酮状态"] end subgraph CellularRepair ["细胞清理与重建"] C --> D["触发伴侣介导的自噬 (CMA)"] D --> E["识别并降解老旧/受损蛋白质"] E --> F["促进蛋白质新生与机体抗衰"] end ``` - 罗根的日常饮食构成以高品质肉类结合发酵蔬菜（如泡菜、酸菜）为主，以此规避血糖大幅波动造成的极端饥饿。 - CMA（Chaperone-Mediated Autophagy）由纽约阿尔伯特·爱因斯坦医学院的安娜·玛丽亚·库尔沃教授深入研究，是细胞清除受损蛋白质的关键路径。 - 辛克莱尔指出，持续三天的断食对于全面激活自噬机制并获得抗衰老回报具有显著意义。 --- ### [01:01:39](https://www.youtube.com/watch?v=hxid7FofhMw&t=3699s) 维持六小时高强度脑力：促智补剂与酮体饮料的实战应用在谈及生酮与饮食控制的即时感受时，罗根认为最大的获益在于“精神敏锐度（Mental acuity）”。在维持这种饮食时，他在播客中的言语组织能力、信息检索速度和专注力都会显著提升。辛克莱尔感同身受地表示，主持播客极为消耗心智，尤其是录制单人节目时，他往往需要凭记忆调动数百篇科研文献的细节。如果录制前没能及时断食，他就会通过饮用外源性酮体（如 Ketone-IQ）来快速提供脑部供能。罗根表示自己也是外源性酮体的忠实拥趸，在解说 UFC 赛事前必定会饮用。UFC 的现场直播往往长达整整六个小时，解说员需要全程保持高度专注，不仅要在高压下实时分析比赛，还要从数以千计的巴西柔术技术位置中瞬间辨认出特定招式（例如迅速看清并叫出“秘鲁绞” Peruvian Necktie）。解说结束后，高强度的脑力消耗往往让他精疲力竭、饥肠辘辘。为了最大限度优化认知状态，罗根还结合使用了好友 Derek 研发的 Gorilla Mind 促智饮品、Alpha Brain Black Label 促智胶囊以及 Neurogum 含咖啡因促智口香糖。 - 解说 UFC 赛事需要连续 6 小时无间断直播，高频调取数以千计的地面格斗细节，是对大脑代谢的极端考验。 - 辛克莱尔与罗根均使用 Ketone-IQ 外源性酮体饮料来应对高强度脑力输出。 - 罗根用于播客和赛事解说的认知增强组合还包括 Gorilla Mind、Alpha Brain Black Label 以及 Neurogum。 --- ### [01:03:44](https://www.youtube.com/watch?v=hxid7FofhMw&t=3824s) 神经兴奋剂、剧烈运动抗时差与激效反应（Hormesis）看到罗根充沛的精力，辛克莱尔原以为他服用了莫达非尼（Modafinil）等促智处方药。罗根澄清自己过去确实用过莫达非尼和阿莫达非尼（Provigil 与 Nuvigil），尤其是在圣地亚哥演出结束后凌晨一点驾车两个半小时回家时，服用该药能让他听着有声书清醒安全地开完全程，且神奇的是随后并不会干扰正常睡眠。然而，正因为其效果太好、令人过于依恋，他选择停止日常使用。辛克莱尔则承认，在跨时区长途旅行需要做学术演讲时，自己会服用阿莫达非尼（Armodafinil）来消除脑雾、克服时差，确保表达精准无误。对于时差问题，罗根首选的“解药”是极端的高强度运动：在 15 至 20 分钟内通过 Airdyne 迎风阻力车进行 Tabata 冲刺，或者进行间歇极短的高强度壶铃训练，将心率强行拉升至 150 乃至 180~190 BPM。这种大汗淋漓、喘不过气的冲击能彻底“重置”身体系统，消除疲劳感。辛克莱尔指出，这正是典型的“激效反应（Hormesis）”——“杀不死你的，会让你更强大”。身体在面临生存压力时会启动自我修复机制。辛克莱尔坦言，自己之所以选择以植物性饮食为主并摄入 NMN 等分子，本质上是在用生化方式模拟这种生存压力，因为他平时总以“太忙”为借口缺乏像罗根那样的高强度锻炼。对此，罗根笑着调侃道：“你有的是钱，给自己请个私教不就解决了。” - 处方药 Provigil（莫达非尼）与 Nuvigil（阿莫达非尼）常被用于对抗极端困倦，辛克莱尔在长途差旅演讲时偶尔使用它重置注意力和消除时差脑雾。 - 罗根倒时差的生理重置法：15-20 分钟极限高强度间歇训练（Tabata 冲刺或高负荷壶铃），将心率推高至 150-190 BPM。 - 辛克莱尔强调，剧烈运动和断食的底层科学逻辑一致，均为激效反应（Hormesis）；他通过植物饮食与 NMN 模拟机体的生存逆境信号。 ### [01:06:22](https://www.youtube.com/watch?v=hxid7FofhMw&t=3982s) 交换条件：健身私教与长寿补剂的约定乔·罗根与大卫·辛克莱在笑声中敲定了一项私下交易：大卫给乔提供一罐他研发的长寿“神奇药水”，而乔则亲自担任大卫的健身私教。乔分享了自己此前指导多位脱口秀喜剧演员朋友的经验，强调对于长期久坐、缺乏运动的人群，健身绝不能一上来就搞魔鬼训练。乔的训练哲学是“温和起步，循序渐进”，绝不能把身体系统逼到极限，“你变健康的过程，必须和你当年慢慢变糟糕的过程一样，都需要时间。” 乔直言，许多健身教练一上来就安排两小时高强度训练，练到学员在垃圾桶边呕吐，结果第二天整个人彻底瘫痪放弃，甚至拉伤肌肉、扭伤背部。相反，正确的做法是每天只做极小负荷的动作——比如 10 个俯卧撑、10 个仰卧起坐、10 个自重深蹲，搭配轻量壶铃高翻（kettlebell cleans）。训练结束时，学员不应感到精疲力竭，而应当感到神清气爽、精力充沛，从而能够日复一日地坚持下去。大卫赞同这种理念，并将其与间歇性断食类比：如果从未练习过断食，绝不可能一上来就直接禁食一到三天。乔随后以他的好友、歌手 Jelly Roll 为例，指出 Jelly Roll 成功减重 250 磅的第一步仅仅是“开始走路”——绕着街区散步、爬楼梯，然后逐步调整饮食，并详细记录下每天的训练内容和身体感受。这种逐步累积的微小习惯能够形成正向动能，避免让人在空腹或进行烈性动感单车 Tabata 冲刺后，大脑一片空白地走进实验室。大卫笑着表示完全接受这个建议，并打趣称下次如果有幸再来上播客，一定会穿一件紧身 T 恤来向两千万听众展示训练成果。 - **极简入门方案**：10 次俯卧撑、10 次仰卧起坐、10 次自重深蹲，加上轻量壶铃动作。 - **核心减重案例**：Jelly Roll 通过最基础的走路起步，逐步改变饮食，最终减重 250 磅。 - **心理机制**：通过记录每日动作与身体反馈，建立可持续的正向动能，拒绝直接进入“新兵训练营”式的自虐模式。 --- ### [01:09:55](https://www.youtube.com/watch?v=hxid7FofhMw&t=4195s) 纯素与吃肉的争论：“丰裕模式”与“逆境模式” 话题随即转向两人的重大分歧——饮食结构。乔敦促大卫放弃“可笑的纯植物饮食”，直言肉类是自然界中营养密度最高的食物，并向大卫极力推荐野鹿肉（elk steak），声称一口吃下去“所有神经突触都会瞬间激活点亮”。大卫虽然表示自己热爱肉类的风味、并不排斥偶尔尝试，但解释自己坚持植物性饮食是基于过去三十年在多种动物模型中观察到的长寿数据。为了解释这一现象，大卫提出了他关于生物体状态的核心理论框架：人体在进化中形成了两种截然不同的生理模式。一种是**丰裕模式**（Abundance Mode），对应于人类祖先猎杀猛犸象后大快朵颐的场景，这种状态下摄入充足的蛋白质与能量，极利于肌肉合成、伤口愈合和组织修复，主导的是“生长”；另一种则是**逆境模式**（Adversity Mode），对应于猎物耗尽、人类不得不四处寻找块茎、浆果糊口并长时间奔跑迁徙的艰难时刻。 ```mermaid flowchart TD accTitle: 生物体的两种生存模式对比 accDescr: 展示丰裕模式与逆境模式在饮食触发、生理机制及健康结局上的差异 subgraph A["丰裕模式 (Abundance Mode)"] A1["充足肉类 / 高蛋白摄入"] --> A2["激活生长信号通路"] A2 --> A3["增强体能 / 增肌修复"] end subgraph B["逆境模式 (Adversity Mode)"] B1["植物饮食 / 热量限制 / 奔跑运动"] --> B2["激活生存与防御机制"] B2 --> B3["延长寿命 / 细胞抗逆"] end ``` 大卫指出，丰裕模式让人更强壮、更适应短期生存，但逆境模式（低热量、轻断食、吃植物、持续运动）激活的是长寿防御机制，两者各有其生理价值。乔对此提出质疑，认为动物实验的结果不能机械照搬到人类身上，并询问这种长寿机制究竟与当前的健康活力（vitality）有何本质区别。 --- ### [01:11:36](https://www.youtube.com/watch?v=hxid7FofhMw&t=4296s) 蓝区神话的破灭与人际关系的终极长寿力量乔进一步对当今长寿界推崇的“蓝区”（Blue Zones）概念提出尖锐抨击，直言其充斥着严重的数据造假。两人谈到近期的调查发现，许多所谓百岁老人的长寿纪录实际上是社会福利欺诈的结果：例如在日本冲绳，部分老人去世后，其家属为了继续冒领养老金支票而刻意瞒报死亡事实，导致人口普查名单上充斥着纸面上的“百岁神仙”。大卫也补充道，包括法国被列为史上最长寿人类（122岁）的让娜·卡尔芒（Jeanne Calment），也存在一种未被彻底证实的猜测，即女儿为了逃避高额遗产税而冒充亡母的身份继续生活。乔和大卫达成共识：人类的绝对生物寿命上限大约在 117 至 118 岁左右，而那些真正活到极致高龄的人往往根本没有严格遵循健康守则，他们抽烟、喝酒、纵情享受生活。乔指出，这表明情绪与社交因素被严重低估了——孤独、绝望和抑郁对健康的杀伤力远超不良生活习惯。大卫随即引用了哈佛大学罗伯特·瓦丁格（Robert Waldinger）主持的长达数十年的成人发展追踪研究。该研究追踪了二战老兵等群体的血压、胆固醇等全方位指标，最终得出的结论是：**预测长寿的最强单一指标，是拥有一个可靠且充满爱意的伴侣**。乔对此深感共鸣，分享了自己结婚 17 年依然深爱妻子、享受彼此陪伴的真实体会，并对比了一位刚从长达 7 年有毒恋爱关系中解脱的 40 岁好友。乔感慨地引用了那句老话：“‘宁可孤身一人，也胜过在一段关系中渴望独自一人’（It's so much better to be alone than to wish you were alone）。” - **长寿神话破绽**：冲绳等蓝区百岁老人激增的背后，存在大量隐瞒死亡冒领养老金的真实案例。 - **让娜·卡尔芒疑云**：官方记录 122 岁的世界纪录保持者，被部分研究者怀疑是女儿为避税顶替母亲身份。 - **哈佛成人发展研究结论**：罗伯特·瓦丁格的研究证明，深厚、可靠的伴侣关系对寿命的保护作用位列第一，超越了传统生理指标。 ### [01:14:23](https://www.youtube.com/watch?v=hxid7FofhMw&t=4463s) 毒性关系与职场高压对生物学时钟的摧残不良的人际关系对身心健康的摧残是致命的，这种压力会直接反映在生物学的衰老层面上。戴维·辛克莱（David Sinclair）指出，科学研究已经证实，当一个人处于重度压力或经历痛苦的分手时，DNA上的表观遗传化学修饰（即衰老时钟）会急剧加速。乔·罗根（Joe Rogan）对此深有感触，他提到看到身边的朋友经历离婚折磨时，整个人看起来瞬间苍老了几十岁，通常需要一到两年时间才能重新找回身心平衡。辛克莱坦言自己在新冠疫情期间也经历过类似的家庭危机，全家人被封控在一栋网络不畅的小房子里，极度压抑的狭小环境引发了意想不到的巨大冲突，好在如今他已走出阴霾并重获幸福。罗根进一步指出，人际关系的毒害不仅局限于恋爱、婚姻或家庭，职场中的恶劣关系同样杀伤力惊人。如果你每天面对一个暴君般的老板，被迫加班、被严厉训斥，甚至回到家还要接电话应对工作，身体在生理层面上根本无法区分恋爱关系和职场关系所带来的创伤，两者产生的破坏力几乎等同。辛克莱补充道，高压状态下人体皮质醇（Cortisol）长期处于高位，这会直接加速机体衰老。他用自己学生时代养鱼的经历打了个生动的比方：鱼缸里那些被优势种欺凌的弱小鱼类不仅体格矮小、体色暗淡，而且寿命往往极短。这完全是客观的生物学规律——被霸凌、长期受压，衰老就会加速。幸运的是，随着年龄与阅历的增长，他们都学会了彻底清除生活中的混蛋，辛克莱现在还找到了一位同为长寿科学专家的伴侣，两人拥有共同的研究志趣与生活爱好。 - **DNA表观遗传时钟加速**：研究表明，心理重压、情感破裂和不良人际关系会直接加快DNA甲基化时钟的走速。 - **职场压力的生物学等价性**：长期遭受暴君式老板虐待所引发的高皮质醇分泌，对人体的损伤与糟糕的婚姻不相上下。 - **5种延长15年寿命的健康基石**：远离不良关系、不吸烟、不酗酒、保证充足睡眠、坚持规律运动。 - **长寿老人的核心特质**：虽然有千分之一（0.01%）的老人即使抽烟喝酒也能长寿（属于罕见的极端基因特例），但绝大多数百岁老人的共同特征是不易焦虑、极富幽默感、从未过度肥胖，且几乎记不得自己上次生病是什么时候。 --- ### [01:18:08](https://www.youtube.com/watch?v=hxid7FofhMw&t=4688s) 社交媒体诱发的应激反应与专注自我的解脱现代人每天被社交网络上的负能量裹挟，无形中在大幅缩短寿命。辛克莱与罗根笑称科学界真该好好立项研究一下“刷推特（Twitter / X）到底会让人折寿多少年”，特别是那些充满恶意的评论区。罗根表示，彻底戒断这些网络杂音后自己的幸福感显著提升。人类的大脑原本是为生活在紧密邻里社区中而设计的，如果每天被动接收全世界每一个角落发生的苦难与灾难，大脑就会持续陷入全天候的“战斗或逃跑”（fight or flight）应激反应。很多人即便身处平静的现实环境，精神世界却被数千里之外的气候危机、地缘冲突和争吵折磨得濒临崩溃。辛克莱指出，世界并不会因为你少看一条推文就发生变化，与其把精力浪费在焦虑宏大议题上，不如专注于自己擅长且真正有益的事业。有人曾站在道德制高点指责辛克莱，质问他“为什么不去解决全球气候变暖”，罗根对此类指责嗤之以鼻，认为要求每个人对所有问题负责是荒谬至极的。社会有不同领域的分工，辛克莱的幽默回应是：“等我治愈了衰老，我再去解决气候变化。” ```mermaid flowchart TD accTitle: 社交媒体压力与身心损耗机制 accDescr: 展示全天候信息过载如何诱发战斗或逃跑反应并导致慢性衰老。 subgraph External["信息过载环境"] A["全球危机/地缘冲突新闻"] B["社交平台恶意评论"] C["气候焦虑与道德绑架"] end subgraph Internal["生理与心理机制"] D["持续触发'战斗或逃跑'反应"] E["皮质醇长期处于高位"] end subgraph Consequence["生物学后果"] F["心智疲惫与焦虑蔓延"] G["表观遗传时钟加速运转"] H["机体生理性衰老加速"] end A --> D B --> D C --> D D --> E E --> F E --> G G --> H ``` --- ### [01:20:04](https://www.youtube.com/watch?v=hxid7FofhMw&t=4804s) 祖母的遗训与对抗死亡的使命感辛克莱研究衰老并非出于偶然，其深层动力源自四岁时祖母带给他的灵魂震撼。他的祖母是二战幸存者，亲历了战火洗礼与苏联军队占领匈牙利时犯下的种种暴行，随后历经艰难辗转逃往澳大利亚。祖母从小灌输给辛克莱两件事：一是人性中有恶的一面，人类为改善世界做得远远不够；二是“所有人终究都会死去”。年仅四岁的辛克莱当即觉得这极不公平，为什么所有生命最终都要屈服于死亡？这个童年困惑深植于他的脑海，成为了他一生科研道路的原动力。对于大多数人而言，每天思考死亡是残忍且沉重的，因此本能地选择遗忘；但对辛克莱而言，全球每天有约15万人死于与衰老相关的慢性疾病，这一冷酷的现实时刻都在鞭策着他的团队。他的实验室因此具有极其强烈的使命感与紧迫感，深知只要研究进度推迟一天，就意味着又有成千上万的人遭受本可避免的病痛折磨。甚至有视障患者亲自赶到他的实验室门前苦苦守候，迫切希望成为逆转衰老基因疗法临床试验的受试者。辛克莱表示，如果这项恢复视力的临床试验取得成功，整个世界的格局都将被改写；即便眼下的试验受挫，底层的科学逻辑也已足够扎实，攻克衰老只是时间早晚的问题。 - **祖母的历史烙印**：二战期间在匈牙利的生存危机塑造了祖母的处世哲学，从而直接启蒙了辛克莱改善世界、挑战死亡的决心。 - **衰老疾病的沉重代价**：全球每天约有15万人因与衰老直接相关的疾病离世。 - **临床试验的前沿突破**：实验室针对细胞逆转与视力恢复的技术已进入临床试验阶段，吸引了大量盲人及退行性疾病患者的高度关注。 --- ### [01:21:49](https://www.youtube.com/watch?v=hxid7FofhMw&t=4909s) 人工智能如何颠覆生物学研究范式当罗根问及AI（人工智能）是否正在对长寿科学带来突破性影响时，辛克莱给出了极为肯定的答复。他强调AI已经彻底颠覆了整个生物学界的研究范式。过去一名研究人员一天顶多硬啃15篇学术论文，如今借助AI的超强理解与信息检索能力，系统可以在极短时间内研读、交叉比对上百万篇文献。这种“超级大脑”的出现，直接将生命科学的数据处理与假设验证速度提升了几个数量级。辛克莱分享了一个正在其实验室发生的生动案例：今年夏天，一名年仅19岁的年轻人加入了他那由20人扩张到40人的研究团队。辛克莱的实验室正试图解开一个前沿生物学谜题——为何仅凭三种山中因子（Yamanaka factors）的重新激活，衰老的细胞就能重置回年轻状态？细胞究竟是如何记住自己30甚至40年前的年轻形态？那份年轻态的信息备份究竟储存在细胞的什么位置？辛克莱提出了一个全新的生物学假说，认为DNA内部存在着某种未被发现的信息记录机制。面对海量未知的机制，他让这位19岁的年轻人直接调用AI模型去检索全球数据库中海量级别（Exabytes，艾字节）的庞大数据，通过计算生物学手段验证他的假说是否能够成立。 ### [01:22:48](https://www.youtube.com/watch?v=hxid7FofhMw&t=4968s) 19岁高中毕业生利用 AI 破解长寿谜题与生物技术两面性戴维·辛克莱尔（David Sinclair）分享了一件令他极为振奋的突破：实验室里一名刚高中毕业的 19 岁实习生，在短短两周内利用 AI 算法处理了海量数据。当团队其他成员带着灿烂笑容把他请进办公室时，显示屏上赫然展示出证实辛克莱尔长寿假说的“确凿证据”（smoking gun）。长期以来，诸多顶尖教授与资深学者苦思无果的核心难题，竟被一个初出茅庐的年轻人借助 AI 工具攻破。辛克莱尔感叹，未来的世界必然属于那些能够熟练驾驭 AI 的人，甚至普通人在手机端也能完成药物的设计与研发。然而，乔·罗根（Joe Rogan）敏锐地指出，技术门槛的骤降也意味着制造炸弹和生物武器的门槛同样大幅降低。两人谈及调查记者安妮·雅各布森（Annie Jacobsen）在播客中关于核战争与生物武器的恐怖警示——她揭露的真相让全世界不寒而栗。辛克莱尔透露，由于自身掌握的技术具备潜在的生物武器制造能力，他在移居美国之初就必须向美国政府进行严格报备；为了防范未来潜在的天然或人造大流行病，他目前正建立一个涵盖所有已知病原体与新型潜在病原体的数据库，以此为全球生物安全尽一份力。 - **AI驱动科学发现**：19 岁研究员利用 AI 工具两周内验证了辛克莱尔理论的核心证据，实现了传统顶尖学者团队多年未能突破的进展。 - **生物技术的双刃剑效应**：手机端设计分子药物的技术同样可被恶意用于设计致命病原体与生物武器。 - **全球病原体数据库**：辛克莱尔团队建立已知及未知潜在病原体数据库，用于预警未来大流行病危机。 --- ### [01:24:21](https://www.youtube.com/watch?v=hxid7FofhMw&t=5061s) 基因“出厂重置”与肢体再生：从蝾螈到“死侍”的现实路径讨论转向机体修复的终极前景。罗根提出，如果人类基因组中确实完整保留着年轻健康状态的“原始备份”，那么通过表观遗传重编程将其激活，就如同对身体进行一次“恢复出厂设置”（factory reboot），理论上不仅能彻底消除所有疾病，甚至能修复严重创伤并重新长出断肢。辛克莱尔对这一设想表示高度认同，并提及近期一项新发表的研究：研究人员仅用两种转录因子，就成功促使幼年小鼠愈合的指尖残端重新长出部分指节。这证明人类体内依然潜藏着保持年轻与身体部位再生的全套分子指令，只是在进化中被永久“关闭”了。不同于经常遭遇断肢掠食因而保留再生能力的蝾螈，哺乳动物在远古生存竞争中选择了“迅速结疤封住伤口并继续逃命”的演化策略。辛克莱尔坚信，结合现有的表观遗传逆转技术与肢体再生新突破，人类未来有望获得如同漫画超级英雄“死侍”（Deadpool）般的自愈能力——无惧衰老与物理创伤，且能再生肢体。他预测人类肢体再生的临床突破在未来数十年内即可实现。从 2019 年在小鼠身上首次证实衰老可逆并公开发表，到短短几年内推进至人体临床试验，衰老生物学的演进速度已远超以往认知。 ```mermaid flowchart TD accTitle: 肢体再生与抗衰演化路径对比 accDescr: 对比蝾螈与哺乳动物应对损伤的策略差异以及现代生物科技重塑人体再生能力的流程 subgraph Nature ["自然界演化策略对比"] Salamander["蝾螈演化路径"] --> S_Regen["遭遇断肢频繁捕食 长期保留全套肢体再生机能"] Mammal["哺乳动物演化路径"] --> M_Scar["追求生存时效 选择快速愈合结痂（关闭再生指令）"] end subgraph FutureTech ["现代表观遗传重编程与再生医学"] Reset["基因组底层原始备份 （出厂设置重置）"] --> Factors["引入关键诱导因子 （小鼠指尖再生实验）"] Factors --> Clinic["终极目标：超越创伤与衰老 实现如死侍般的自愈与肢体再生"] end Nature --> FutureTech ``` --- ### [01:26:48](https://www.youtube.com/watch?v=hxid7FofhMw&t=5208s) 科技巨头入局抗衰赛道：百亿资本涌入重编程研发伴随抗衰老从理论假说转入人体临床试验，全球资本与顶尖科技巨头纷纷重金下场。辛克莱尔创立的 Life Biosciences 正在推进候选药物 ER-100 的人体试验，与此同时，一批拥有巨额资金支持的强劲竞争对手相继涌现：亚马逊创始人杰夫·贝索斯（Jeff Bezos）联合创立了跨国研发布局的 Altos Labs（注：音频口误为 Eltos Pharma），注资数十亿美元；OpenAI 首席执行官山姆·奥特曼（Sam Altman）大笔投资了 Retro Biosciences；Coinbase 首席执行官布莱恩·阿姆斯特朗（Brian Armstrong）则联合创立了抗衰生物技术公司 NewLimit。面对这些携数十亿美元杀入战场的竞争者，辛克莱尔表现得非常豁达与欢迎。他直言，自己的初衷并非追逐个人商业利益，而是渴望推动整个人类命运的根本改变；对于贝索斯这样拥有无尽财富的人而言，在探索太空之外，投入资金去逆转衰老、根除疾病和再生肢体，本身就是对人类文明最有价值的贡献。虽然这项宏伟事业可能无法在辛克莱尔有生之年完全实现，但全球顶尖智慧与数百亿美元资本的合流，已经不可逆转地将抗衰老医学推向了前沿拐点。 | 机构 / 团队 | 核心领投 / 创始人 | 重点技术方向与资本布局 | |:--- |:--- |:--- | | **Life Biosciences** | 戴维·辛克莱尔（David Sinclair） | 推进 ER-100 人体临床试验，专注于表观遗传重编程逆转衰老 | | **Altos Labs** | 杰夫·贝索斯（Jeff Bezos）等 | 斥资数十亿美元，在全球三大城市设立研发中心，攻坚细胞逆龄转化 | | **Retro Biosciences** | 山姆·奥特曼（Sam Altman） | 获得数亿美元战略注资，主攻细胞重编程与健康寿命大幅延长 | | **NewLimit** | 布莱恩·阿姆斯特朗（Brian Armstrong，Coinbase CEO） | 聚焦单细胞表观基因组学，利用重编程技术靶向攻克衰老退行机制 | --- ### [01:28:24](https://www.youtube.com/watch?v=hxid7FofhMw&t=5304s) 意识工程、精神困境与迷幻药革命：从伊博格碱到无致幻分子谈话从生理肉体进一步延伸至精神与意识层面。罗根提出设想：未来人类是否能像工程化操控肉体一样去“工程化操控意识”——例如通过神经回路精准测绘，直接排查反社会人格、偷窃癖或纵火狂等心理与行为缺陷的神经传导故障。辛克莱尔对此毫不怀疑，他认为意识本质上同样是生物学与工程学机制，本世纪人类终将实现对自身生物机能的全面控制。不过，相较于消除衰老与心脑血管疾病，辛克莱尔幽默地指出“战胜衰老可能比实现世界和平要容易得多”。罗根随即提出，实现广泛共情或许可以通过致幻植物（如迷幻蘑菇）来达成。当前制药工业对致幻剂的接纳程度正在经历剧变，如大型药企正斥资数十亿美元收购或投资相关研发管线（如涉足 ATAI Life Sciences 等致幻剂研发实体）。罗根回顾了自己前往白宫游说、推动总统就伊博格碱（Ibogaine）签署行政指令的经历。伊博格碱提取自西非传统灌木，对阿片类药物成瘾以及创伤性脑损伤（TBI）、慢性创伤性脑病变（CTE）展现出不可思议的神经逆转疗效，然而该物质长期被美国无端列为无医疗价值且不可使用的“附表一管制药物”（Schedule I）。尽管其服用过程长达 24 小时且体验极度煎熬痛苦，绝无任何滥用和成瘾可能，却长期受到严厉封禁。辛克莱尔与罗根共同探讨了一个前沿科学问题：患者是否必须亲身经历恐怖强烈的致幻“旅程”（trip）才能获得神经重塑与治疗收益？辛克莱尔坚信两者在分子机制上可以剥离，而罗根提到科研人员已在实验室成功合成出剥离了致幻副作用、仅保留认知修复与神经可塑性益处的非致幻新型 LSD 类似物。 ### [01:31:27](https://www.youtube.com/watch?v=hxid7FofhMw&t=5487s) 从柳树皮到迷幻药改造：药物审批与辨人哲学乔·罗根与大卫·辛克莱探讨了迷幻药去致幻化改造的前景：是否可能制造出一种保留 LSD 积极认知重塑、内省与神经重构能力，却完全剔除“面部融化、恶魔吞噬”等可怕幻觉反应的药物。辛克莱对此大加赞赏，认为这正是整个现代医学的演进路径——正如人类最初通过咀嚼柳树皮止痛，随后提炼合成了阿司匹林，“我们现在不会直接啃树皮了”。罗根对此提出另一面隐忧：许多大型制药企业热衷于将天然成分申请专利，通过石油基合成手段制造高价药物以攫取暴利，而在很多时候原生植物本身反而是更好的选择。然而辛克莱指出，未获审批的天然成分会导致市场沦为“法外狂徒式的荒野西部”，消费者根本无法确认产品的真实剂量与成分，行业亟需一种既能安全迅速推向市场、又能提供确定品质的中间路线。谈话随即转入对欺骗与谎言的探讨。罗根打趣说，人类最迫切需要的其实是一台“谎言探测器”或读心术。辛克莱表示罗根在播客主持中已经展现出极敏锐的辨伪能力，罗根则坦言尽管阅人无数，有时仍会被某些善于伪装的人蒙蔽。他谈到，在长达三小时的深入对谈中，一个人的真实面貌很难隐藏，主持时必须保持适度宽容，理解很多人只是因为紧张才出现口误、夸大或遗忘；但真正可怕的是那些“除了自己之外完全不在乎任何人”的自私个体，这群人甚至掌握了极其精湛的伪装技巧，能够毫无破绽地演扮成一个正常人。 ### [01:33:40](https://www.youtube.com/watch?v=hxid7FofhMw&t=5620s) UC Davis 的无致幻 LSD 类似物 JRT 与 AI 搜索的颠覆罗根调出了一项令人瞩目的最新神经科学成果：加利福尼亚大学戴维斯分校（UC Davis）的科学家在《美国国家科学院院刊》（PNAS）上发表论文，成功合成出名为 (±)-JRT 的 LSD 化学类似物。研究人员仅仅对分子结构中的两个原子位置进行了调换，这种微调使 JRT 能够以更高的选择性与五羟色胺受体结合，一方面强烈激活神经元突触的可塑性、突触生长与损伤修复，另一方面几乎完全阻断了致幻信号的产生。 ```mermaid flowchart LR accTitle: LSD与改造分子JRT的机制对比 accDescr: 展示加州大学戴维斯分校科学家微调LSD分子结构以分离神经修复与致幻作用的路径。 subgraph MOD["分子结构改造"] LSD["经典致幻剂 LSD"] -->|"调换2个原子位置"| JRT["LSD 类似物 (±)-JRT"] end subgraph MECH["受体结合机制"] JRT -->|"高选择性靶向"| 5HT["五羟色胺受体通路"] end subgraph OUT["神经与临床效应"] 5HT --> E1["促进突触生长与神经可塑性"] 5HT --> E2["超强抗抑郁 (啮齿动物模型中达氯胺酮100倍)"] 5HT --> E3["大幅抑制或消除致幻体验"] end ``` 罗根惊叹于动物实验的数据：该化合物在标准啮齿动物测试中展现出极强的抗抑郁效果，药效据报道达到氯胺酮（ketamine）的约 100 倍，并且在模拟精神分裂症认知障碍与负性症状的模型中，显著提升了认知灵活性与测试表现。罗根特别赞许了本期节目的赞助商 Perplexity AI，感叹以往在 Google 上检索必须逐一筛选嘈杂的网页与混乱的信息源，而现在利用 AI 能即刻精准调取最前沿的论文背景。辛克莱指出，从动物实验成功到药物真正上市通常至少还需要 5 年以上，但这项研究从原理上彻底证明了“无需经历致幻旅程即可收获神经修复益处”的可行性，对于饱受精神分裂症摧残的患者及其家庭而言，具有革命性的意义。 - 分子结构优化：通过仅调整 2 个原子的位置，大幅降低了致幻通路信号。 - 突触重塑活性：保留了促进大脑神经可塑性、神经突触修复与轴突再生的特性。 - 超强抗抑郁潜力：在动物模型中的抗抑郁效力达到氯胺酮的约 100 倍。 - 精神分裂症认知改善：改善了模拟精神分裂症负性症状与认知缺失的任务表现。 - 临床转化周期：辛克莱评估按照通常的药物研发规律，距离商业化至少还需 5 年左右。 ### [01:36:01](https://www.youtube.com/watch?v=hxid7FofhMw&t=5761s) 脑机接口、意识互联与全球通用语言的局限围绕“识别谎言”的话题，辛克莱畅想未来或许可以通过 AI 探测并在每个人的额头上投射红绿灯提示。罗根则认为，未来人类终究会通过某种技术手段直接读取思维的内容，这并非天方夜谭。针对辛克莱“可能需要植入物”的判断，罗根提到埃隆·马斯克正致力于通过 Neuralink 脑机接口实现无需语言的直接意念交流，甚至可能使全人类联结为一个群体蜂巢思维（hive mind）。两人随之探讨了全球通用语言的演变。尽管辛克莱提及某科技巨头推出的翻译耳机已经能实现实时跨语言转译，但罗根指出，机器翻译往往会丧失特定文化深处的语境、隐喻与微妙情感，生硬翻译会显得十分怪异，因此一种真正全球统一的共同语言依然具有不可替代的价值。辛克莱感叹英语在国际旅行中的高度普及，罗根幽默地称这是“美国统治全球”的体现；辛克莱随即纠正笑称应该先感谢英国人打下的基础，罗根则风趣回应英国只是负责开局，是美国接过了接力棒将其推广到全球。谈及中文是否可能成为下一个世界通用语言时，罗根表示自己身边精通中文口语的朋友都无法书写汉字，庞大而复杂的汉字书写系统对于非母语者而言是一道难以逾越的高门槛。 ### [01:37:58](https://www.youtube.com/watch?v=hxid7FofhMw&t=5878s) 顶尖学术实验室的科研审查与美澳创投文化的鲜明对比话题转入跨国科研人才流动。辛克莱透露，他实验室里来自中国的留学生虽然在签证与移民环节面临严厉的审查与挑刺，但他们极度热爱这里的科研环境、普遍不愿回国。面对罗根关于技术机密窃取风险的提醒，辛克莱承认目前针对科学家的监管与背景审查极其严苛，每一位进入核心实验室的人员都必须经过详尽的安全背调。作为一名从澳大利亚赴美发展的移民科学家，辛克莱深情对比了两国的文化土壤。尽管澳大利亚十分自由安逸，但与美国相比仍有本质区别：在美国，只要倾注心血、拥有绝妙的想法，个人就不会受到阶级或资金的束缚，能迅速获得创立公司的机会；而在澳大利亚，本土投资者普遍极度规避风险，罕有人愿意为冒险想法下注。辛克莱感慨，全世界大部分地区的人哪怕手里有钱，也总是战战兢兢害怕亏损，只有美国拥有庞大流动资本和一种罕见的慷慨冒险精神——投资者愿意承担血本无归的风险，并在失败后依然自豪地认为“自己冒了险并曾试图推动世界改变”。罗根深表赞同，他认为许多人对美国的批评主要集中在外交政策等方面，但从大局来看，这项即将迎来 250 周年的自我治理制度实验，依然是人类历史上令人惊叹的伟大成就。 ### [01:39:54](https://www.youtube.com/watch?v=hxid7FofhMw&t=5994s) 美国建国先贤的历史机缘与法国的恩怨乔·罗根与大卫·辛克莱聊起了关于美国建国先贤的影视纪录片。罗根感叹，除了本杰明·富兰克林（Benjamin Franklin）当时算是个老者之外，其他绝大多数起草宪法、发起革命的先贤们其实不过是二三十岁的年轻小伙子。他们置身于风暴的中心，虽然隐约意识到自己正在创造历史，但整个建国历程充满了凶险与未知——只要有几张选票投向相反的方向，或者某几场关键战役的结果反转，美利坚合众国就根本不会存在。大卫补充指出，在独立战争早期，美军面对英国军队几乎是一路惨败。话题随后转到了法国在独立战争中的关键角色。两人调侃道，美国人其实从来没有给过法国人足够的感谢，甚至不知从何时起，法国在某些美国文化语境中反而成了嘲讽的对象。罗根回忆起海湾战争期间，由于法国反对美国的军事行动，美国一些餐厅甚至愤而将法式薯条（French fries）改名为“自由薯条”（Freedom fries）。大卫笑着表示大家常常吐槽法国人傲慢，而罗根则反驳道，通常一个人或民族表现出傲慢，是因为他们历史上确实干过极其牛气的大事——比如在19世纪横扫欧洲的拿破仑战争。 --- ### [01:41:00](https://www.youtube.com/watch?v=hxid7FofhMw&t=6060s) 多巴胺受体基因 DRD4-7R 与“叛逆冒险”天性罗根借由 Perplexity 搜索了一个话题：“美国人身上是否存在某种冒险基因？”搜索结果引出了神经科学与遗传学界深入研究的多巴胺受体基因变异体——DRD4 的 7 重复序列版本（7R variant）。该基因变异与探索新鲜事物（novelty seeking）、冲动性以及高风险的财务或社会决策密切相关。尤为惊人的是它在全球人口中极不均衡的分布特征：在美洲原住民及迁移群体中，约 48% 的受测染色体带有该变异，而在东亚人群中，这一比例仅有约 2%。进化人类学的研究表明，在人类祖先走出非洲后，迁徙距离越遥远的族群，DRD4-7R 基因的携带比例往往越高。罗根由此推论，那些当年敢于冒着生命危险飘洋过海来到美洲新大陆的人，天然就带有这种敢打敢拼、孤注一掷的基因底色。大卫对此深表赞同，并透露自己正在撰写的新书中就重点写到了这个基因。大卫戏称其为“去你的基因”（the FU gene），认为正是这种渴望探索、打破规则的特质让人类超越了其他物种。大卫进一步解释，该基因在青少年时期会被显著激活，直到成年后才逐渐下调；这在进化上其实是一种促使孩子“离巢”的生理机制，让青少年本能地看父母不顺眼并渴望自立门户。 ```mermaid flowchart TD accTitle: DRD4-7R 基因机制与迁徙演化 accDescr: 展示 DRD4-7R 基因从进化迁徙到青少年行为表达的生理与社会机制 subgraph Evolution ["演化与迁徙分布"] A["走出非洲的远途迁徙"] --> B["DRD4-7R 频率显著上升"] B --> C1["美洲人群: 约 48%"] B --> C2["东亚人群: 约 2%"] end subgraph Behavior ["生理表达与行为结果"] D["青春期基因激活"] --> E["寻求新奇与冲动冒险"] E --> F["对父母产生叛逆感 ('FU Gene')"] F --> G["脱离原生家庭、探索新世界"] end Evolution -.-> Behavior ``` - **DRD4-7R 特征**：多巴胺受体基因的 7 次重复变异，与高探索欲、冲动和承担社会/财务风险直接相关。 - **地理分布差异**：美洲样本中携带率接近 48%，东亚仅约 2%，与人类从非洲迁徙的最远距离呈正相关。 - **生理调控**：青春期阶段该基因表达上调，促使个体脱离家庭庇护，走向独立生存与探索。 --- ### [01:42:57](https://www.youtube.com/watch?v=hxid7FofhMw&t=6177s) 父母教育之道：做导师而非权威暴君在谈到青少年的逆反期时，罗根分享了自己的育儿观念。他作为父亲，极为警惕将自己的意愿强加在孩子身上，既不强迫他们做不喜欢的事，也不把孩子推向特定的人生轨道，而是鼓励他们追随自己的兴趣去尝试和冒险。当孩子犯错需要纠正时，罗根绝不会摆出“因为我是你爹，所以你必须听我的”那套陈腐架子，而是坦白告诉孩子：自己当年犯过更愚蠢的错误、对父母老师撒过谎、把所有事情都搞砸过，自己只是出于爱和人生阅历提供参考，希望孩子少走弯路。大卫对罗根的育儿方式深表赞同，并分享了自己与 19 岁儿子本杰明（Benjamin）之间的一段真实经历。本杰明利用暑假给大卫打工，协助制作播客和即将推出的新杂志，但有一段时间工作松懈，整整一周没有在社交媒体发布内容。大卫当时面临选择：是像对待普通雇员那样严厉斥责，还是采取不同的方式？大卫选择了克制，他找儿子坦诚沟通：“你在健身房练得很棒，微积分也学得极好，但在这项工作上你确实没做好。到底发生了什么？”这种基于肯定与尊重的交流让父子关系更加紧密，本杰明随后迅速改进了工作状态。 --- ### [01:45:20](https://www.youtube.com/watch?v=hxid7FofhMw&t=6320s) 避免代际创伤：以真诚沟通替代居高临下的管教罗根与大卫深入探讨了传统粗暴管教方式带来的危害。罗根指出，老一辈那种大喊大叫、摔东西甚至动辄体罚的管教手段，或许偶尔能起到震慑作用，但它是一件粗钝的钝器，不仅无法让孩子心服口服，反而会在他们心中埋下深深的创伤与长期的敌意。孩子最终只会变得充满愤怒，而无法从父母那里吸收宝贵的人生经验。两人达成共识：父母的角色应当是“导师”（mentor），既不能退化为毫无规矩的“死党”，也不能沦为发号施令的独裁者。大卫询问罗根的孩子成长情况，罗根欣慰地表示孩子们非常优秀、专注且充满上进心，甚至从未经历过那种仇视父母的极端叛逆期。面对大卫调侃“也许他们缺少那个强烈的 DRD4 叛逆基因”，罗根坚持认为沟通方式起到了决定性作用——父母必须放下虚伪的威严，承认自己从不是完美无瑕的圣人，哪怕是小时候把饭扔在地上这种荒唐事也同样干过。大卫感慨地反省道，自己在抚养第一个孩子时盲目沿袭了父母死板严肃的管教方式，导致大孩子至今性格依然较为叛逆、与他有些疏远；直到抚养第三个孩子时他才明白这个道理，转变了教育方式。 ### [01:48:26](https://www.youtube.com/watch?v=hxid7FofhMw&t=6506s) 育儿之道：从“证明给世界看”到激发内生热情与阅读习惯谈及下一代的教育与动力来源，乔·罗根（Joe Rogan）反思了传统的严厉管教方式。他坦言自己小时候总憋着一股“我一定要证明给你们看”的狠劲，曾以为如果不严格要求、让孩子过得太舒服会毁掉他们的斗志。然而现实打破了他的偏见——健康的心态并非源于复仇式的证明欲，而是来自对事物的真正热情与创造力所带来的满足感。大卫·辛克莱（David Sinclair）深表赞同，并分享了他带儿子本（Ben）一起工作的经历：他希望儿子能近距离感受创业者的生活状态，明白开创一番事业不仅充满挑战，而且“工作本身可以非常有趣”。辛克莱指出，很多年轻人缺乏这种见识，而父母最重要的职责就是为他们打开眼界。两人还探讨了信息时代的利与弊。罗根指出，尽管并非每个孩子都能在家庭中获得这种熏陶，但互联网、播客和 YouTube 让现代年轻人能够接触到多元的顶级视角，随时汲取有用的思维工具。与此同时，辛克莱特别强调了抵御社交媒体算法诱惑、培养阅读习惯的重要性。由于看到孩子们整天抱着手机无休止地滑动屏幕，辛克莱特意给家里订阅了《国家地理》（National Geographic）杂志，试图用图文阅读留住这项濒临失传的能力。罗根承认自己目前摄入的信息有 90% 依赖音频。他通常利用开车、健身、蒸桑拿、躺高压氧舱或做红光理疗的碎片时间听书。虽然他认为听书的吸收效果可能只有深度精读的 70%，缺少了那种独自沉浸、调动大脑特定机制的互动深度，但在生活节奏极其繁忙的情况下，这依然是最高效的选择；而在如今的生活中，翻开一本纸质书往往成了罗根最立竿见影的“助眠神器”。 - **现代视野获取**：即便没有家庭资源支持，年轻人也可以通过网络播客与高质量访谈吸收多元认知工具。 - **保护阅读习惯**：辛克莱通过订阅《国家地理》等优质杂志，帮助孩子对抗短视频和社交媒体的即时多巴胺成瘾。 - **听书与精读的差异**：罗根认为听书能达到约 70% 的阅读效果，适合多任务并行，但无法完全取代无声默读时的大脑专注机制。 --- ### [01:51:38](https://www.youtube.com/watch?v=hxid7FofhMw&t=6698s) 红光疗法奇迹：摆脱老花镜的亲身体验与设备选择当辛克莱感叹随着年龄增长视力开始衰退、看书变得吃力时，罗根兴奋地分享了自己依靠红光疗法（Red Light Therapy）逆转老花的亲身经历。罗根表示，很多人对红光改善视力持怀疑态度，甚至以为他在胡说八道，但他现在确实已经彻底告别了曾经随处乱扔的老花镜。这一转变并非一蹴而就：在刚开始接触全身红光理疗舱时，由于他没有闭眼，视线一度感觉更加模糊，他还曾暗骂自己是不是被忽悠搞坏了眼睛。然而坚持数月后微小的改善开始显现，大约一年后迎来了质的飞跃，视力恢复到了远胜 50 岁时的水平。关于治疗频率，罗根透露自己每周至少进行 3 次，状态好时会做到 5 次，每次在红光舱里躺 20 分钟（无论睁眼、闭眼甚至戴眼罩都能起效）。面对辛克莱关于普通人难以负担昂贵理疗舱的疑问，罗根提到自己最初是从小型家用面板起步的，比如早年赞助过节目的品牌 Joovv（提供医用级红光与近红外光板），站在面板前同样有效。后来，罗根从加里·布雷卡（Gary Brecka）的公司购置了类似于大型日晒床的全身红光舱，不仅视力得到了显著提升，全身胶原蛋白与皮肤状态也获得了肉眼可见的改善。 ```mermaid flowchart TD accTitle: 红光疗法改善视力进程 accDescr: 展示从初期视力恶化到使用红光设备并最终摆脱老花镜的完整体验路径 subgraph Problem ["视力衰退困境"] A["老花加深 度数从 1.0 升至 2.5"] --> B["不戴老花镜 无法阅读邮件与手机"] end subgraph Intervention ["红光干预方案"] C["设备选择 Joovv 光板 / 全身红光舱"] D["使用频率 每周 3 至 5 次，每次 20 分钟"] C --> D end subgraph Progression ["阶段性反应与转折"] E["初期适应阶段 短暂视线模糊，产生怀疑"] F["数月积累 出现细微视力改善"] G["坚持一年以上 彻底摆脱老花镜，晶状阅读无压力"] E --> F --> G end Problem --> Intervention Intervention --> Progression ``` - **老花镜度数演变**：罗根的老花镜度数曾从 1.0 逐步恶化到 2.0 再到 2.5，离开眼镜连手机邮件都无法阅读；目前近距离文字已完全清晰。 - **设备类型跨度**：从立式近红外光板（如 Joovv）到全身光疗舱均具疗效，不必受限于昂贵的专业级舱体。 - **附带效益**：除了显著逆转眼部退化，红光与近红外光还能促进皮肤胶原蛋白生成，提升整体气色。 --- ### [01:54:03](https://www.youtube.com/watch?v=hxid7FofhMw&t=6843s) 线粒体供能、眼部抗衰机制与黄斑营养补充剂辛克莱从分子生物学角度肯定了罗根的体验。他解释道，十年前红光疗法的科学机理尚不明朗，但如今研究已经证实，特定波长（尤其是近红外光）能直接激活细胞内的线粒体（Mitochondria）。有趣的是，辛克莱指出红光激活能量通路的机制在生化层面甚至与伟哥（Viagra）有异曲同工之处。人眼是全身对线粒体能量依赖最高的器官之一，衰老导致的视力下降很大程度上正是由于眼部线粒体无法产生足够的能量（ATP）来支持感光细胞的高强度运转。辛克莱自己虽然没有养成固定的全身光疗习惯，但也会在淋浴时打开红光光砖，并使用生发红光帽（偶尔拉低照亮眼部与面部），虽然外表看起来“像漫画里的末日博士（Doctor Doom）或外星人”，且照完后眼前会有短暂的光斑，但科学依据是扎实的。随后话题转向眼部补充剂，罗根提到自己长期服用 Pure Encapsulations 的黄斑支持配方（Macular Support），主要成分包含叶黄素（Lutein）等抗氧化成分。辛克莱证实了临床试验对眼部营养素的支持，特别是叶黄素、玉米黄质（Zeaxanthin）以及虾青素（Astaxanthin），这些成分对于维护视网膜和黄斑健康具有确切证据。最后，辛克莱笑称自己的裸眼视力目前依然接近完美、无需配镜，唯一的岁月痕迹体现在暗光环境下：当在灯光昏暗的餐厅里孩子们能轻松看清菜单而自己辨认吃力时，确实会感到有些尴尬。 - **线粒体与视力衰老**：眼睛是体内代谢最旺盛的组织之一，近红外光通过激发线粒体能量合成，从根源上延缓感光系统的机能衰竭。 - **关键护眼抗衰成分**： - **叶黄素（Lutein）与玉米黄质（Zeaxanthin）**：过滤蓝光、抗氧化，临床验证可保护视网膜与黄斑区。 - **虾青素（Astaxanthin）**：强效抗氧化剂，辅助缓解视疲劳与眼部细胞应激。 - **昏暗光线适应力（Low-light Vision）**：随着晶状体硬化与视锥/视杆细胞衰退，暗光阅读障碍往往是眼部衰老最普遍的早期信号。 ### [01:57:02](https://www.youtube.com/watch?v=hxid7FofhMw&t=7022s) 视网膜神经的年轻化修复与细胞记忆讨论从人眼随衰老而视力衰退的机制展开。Joe Rogan 提到自己甚至看不清文字，询问背后的根本原因。David Sinclair 解释称，根据其哈佛实验室的系列研究，视网膜内拥有数以万计负责捕捉光线末梢神经。随着机体衰老，这些神经元逐渐丧失了自身的细胞身份，无法正常工作。而他们所开发的基因重编程疗法，能够将这些受损衰老的神经重新唤醒，使其恢复为具有完整功能的年轻神经，这就是在小鼠和猴子实验中能够彻底逆转失明、让动物重获完美视力的原因。 Sinclair 进一步阐述，他和 Rogan 两人的年龄相差大约 22 个月，在他们的眼球内，大约有一半的视神经元已经“遗忘”了该如何正确工作。这项技术的核心逻辑并不是补充新细胞，因为那些神经并没有死亡或消失，它们仍然完好地待在原处，只是需要外界信号重新“提醒”它们找回最初的工作状态。这一原理同样适用于人体的诸多器官与组织：大部分细胞在衰老时并未真正消亡，只需被重新编程唤醒。 ```mermaid flowchart LR accTitle: 细胞重编程逆转衰老机制 accDescr: 展示衰老细胞通过转录因子重编程唤醒原始身份并恢复功能的过程。 subgraph Aging["衰老阶段"] A["衰老/受损细胞"] --> B["细胞身份遗忘 功能退化但未死亡"] end subgraph Therapy["重编程干预"] B --> C["诱导表达年轻化转录因子 （三因子重编程）"] end subgraph Restoration["恢复阶段"] C --> D["重置表观遗传时钟"] D --> E["找回年轻组织身份与功能 （如小鼠/猴视力恢复）"] end ``` ### [01:57:59](https://www.youtube.com/watch?v=hxid7FofhMw&t=7079s) 癌症疑虑、发育不良与逆转肿瘤的意外发现当 Rogan 追问这项研究最大的潜在风险与负面后果、Sinclair 深夜辗转反侧最担忧的问题是否是“诱发癌症”时，Sinclair 坦言癌症确实是首要担忧。如果重编程过程推得过远，细胞可能会陷入发育不良（dysplasia），引发细胞异常分化并失控增殖扩散。正如他此前反复警告的“千万不要把我彻底变回婴儿”，山中伸弥（Shinya Yamanaka）凭借全套因子诱导多能干细胞获得了诺贝尔奖，但若在体内直接产生未分化的干细胞团，就会导致畸胎瘤等灾难性后果。不过，实验室的长期动物模型带来了极其振奋的安全数据： - 他们让小鼠眼部的基因治疗持续表达长达 21 个月，并在另一些小鼠体内维持全身性表达达 19 个月。 - 实验结果显示，这些细胞从未退化为无序的多能干细胞，接受治疗的小鼠体内出现的肿瘤甚至少于未接受治疗的对照组。 - 实验室的博士生 Natal 取得了一项意外的突破发现：当将这三种重编程基因引入生长在小鼠体内的人类癌症细胞与肿瘤时，肿瘤不仅没有恶化，反而出现了萎缩。 Sinclair 解释其内在逻辑是：当癌细胞被强行唤醒时，它们忽然“意识到”自己本应是一个正常的细胞（比如肝细胞），进而识别到自身异常的分裂状态，随即启动程序性凋亡（apoptosis），实现“细胞意识到自己三十年前的本来身份，然后自我了断”。 ### [01:59:32](https://www.youtube.com/watch?v=hxid7FofhMw&t=7172s) 哈佛资金断裂危机与独立社群筹款谈及目前实验室想做却受制于现实的科研规划时，Sinclair 透露其实验室在去年遭遇了惨重的科研经费归零危机，几乎全靠私人捐赠才勉强维持运转。面对 Rogan 关于资金断供是否与联邦援助政策相关的疑问，Sinclair 提到哈佛大学与联邦政府之间爆发的激烈冲突，导致哈佛医学院的多项联邦资助全线中断。Rogan 追问这是否与哈佛前校长在国会就校园反犹言论听证会上的争议表现有关，Sinclair 谨慎回应称“据传是这样，但我不想卷入政治站队”，但那场风波几乎迫使他解雇实验室的大多数研究员。在那段极度艰难的时期，Sinclair 依靠个人募款成功挽救了团队，目前实验室彻底摆脱了联邦政府的资金依赖，转由民间捐赠支持。他表示绝大多数科学家并不具备这样的个人号召力和筹款渠道，因此他正通过基金会筹集资金来资助同行科学家。针对自身的研究愿景，Sinclair 感慨最大的遗憾是“进展还不够快”： - 迫切需要并行探索多种抗衰老途径，而不是孤注一掷只有“一次射门机会”。 - 若能注入充足的资金，团队能够迅速开展针对不同人体组织甚至全身性器官重编程的大规模临床试验。 ### [02:01:08](https://www.youtube.com/watch?v=hxid7FofhMw&t=7268s) 《Lifespan》杂志发布与《国家地理》封面为了构建不受制于自上而下官僚体系的抗衰老生态，Sinclair 建立了 lifespan.com 平台，试图自下而上凝聚全球数百万人的长寿健康社群。在现场，Sinclair 拿出了一份精心准备的特殊礼物赠予 Rogan，以感谢他多年来对科学普及与该实验室工作的支持：这是一本第一期创刊号的《Lifespan》杂志，且 Sinclair 专门为 Rogan 定制了一款独特的奢华丝绒（velour）封面。 Sinclair 指出，大众媒体上绝大多数科学报道均出自缺乏专业知识的记者之手，充斥着误解与偏差；而《Lifespan》完全由专业一线科学家亲自执笔撰写，旨在向公众传达值得信赖的前沿科学。杂志的标语印在显眼位置：“Life's too short. Let's fix that.”（生命太短暂，让我们来修复它）。Sinclair 还在节目中分享了一个巧合喜讯：就在录制当天，哈佛实验室关于逆转衰老的研究正式登上了《国家地理》（National Geographic）杂志的封面。编辑部在得知他要参加 Joe Rogan 的播客后，特意提前推出了该期封面报道。 ### [02:03:39](https://www.youtube.com/watch?v=hxid7FofhMw&t=7419s) 结合 AI 与机器人加速转化：打破抗衰研发瓶颈讨论最后转向了如果拥有无限资源和宽松监管环境下的理想研发图景。Rogan 调侃是否可以像《莫罗博士之岛》那样打破条条框框进行极限加速。Sinclair 回应称，在不被大学开除的前提下，最理想的路径是实现高通量管线作业：借助人工智能源源不断预测和生成新型候选分子药物，再以高度自动化的流程迅速完成从小鼠、猴子到人体的多线递进测试。 Sinclair 强调目前的开发周期令人痛心。从他们最初在《自然》（Nature）杂志发表重编程逆转衰老的里程碑突破至今，已经耗费了将近十年时间，而在全球范围内，每天有大约 15 万人因衰老及相关退行性疾病离世。尽管 Sinclair 位于波士顿的衍生公司在重编程赛道上起步最早且领跑全行业，但相比于杰夫·贝佐斯（Jeff Bezos）等人投资的大体量巨头，他们的资金规模仍然相当有限。 - **AI 药物管线标杆**：Sinclair 举了好友 Alex Zhavoronkov（英矽智能 Insilico Medicine 创始人）的例子。Alex 的企业通过由人工智能和全自动化机器人实验室驱动研发，已经推进到了第 35 款在研药物，公司估值数十亿美元。 - **终极构想**：Sinclair 希望将这种基于 AI 筛选与全自动化机器人驱动的高速实验闭环，全面移植到细胞重编程抗衰老领域，实现多个靶点、多种组织并发推进的大规模并行研发。 ### [02:06:01](https://www.youtube.com/watch?v=hxid7FofhMw&t=7561s) 实验室预算与健康常态的珍贵大卫·辛克莱尔（David Sinclair）谈到了长寿科研面临的资源瓶颈。他指出，自己在哈佛医学院实验室的年预算目前只有 300 多万美元出头。与衰老研究若取得突破后能带来的巨大经济回报相比——仅在美国就能节省数万亿美元的医疗开支——这点预算微不足道。如果能获得更多资金和研究资源来开展各项临床实验，将对全人类产生改变一生的深远影响。乔·罗根（Joe Rogan）随之感慨，没有人希望衰老或生病，健康的身体才能带来无与伦比的行动效率。两人探讨了现代人对健康“身在福中不知福”的普遍心理。人们往往只有在生病、萎靡不振时，才会猛然想起健康是多么宝贵的财富。罗根分享了自己最近的经历：他在一周半前刚从意大利出差回国，由于时差反应和睡眠紊乱，加上连续几天高强度的健身训练和不间断的工作，终于在某一天彻底崩溃，整个人“感觉糟透了”。他不得不推掉所有安排，窝在电视机前休息，心里唯一的念头就是“真希望赶紧好起来”。辛克莱尔提醒道，这种糟糕甚至衰弱的状态，其实正是老年人和体弱多病者每天面对的现实，而目前大部分人对此束手无策。 - 辛克莱尔实验室目前的年科研预算约为 300 多万美元，相较于其在全美乃至全球范围内潜在节约的数万亿美元医疗支出，这一数字极低。 - 罗根分享刚从意大利回国后的重度时差与疲劳体验，说明失去健康活力时日常机能所受到的严重阻碍。 --- ### [02:07:33](https://www.youtube.com/watch?v=hxid7FofhMw&t=7653s) 饮酒对衰老的加速与精力的代偿代价在谈及健康容易被透支时，酒精成为了讨论的核心。罗根指出，许多人借着身体健康四处狂饮，用一整夜的酒精毒害身体来换取短暂的放纵。辛克莱尔严肃警告，这种行为不仅得不偿失，还会大幅加速衰老过程。他经常告诫自己的孩子：哪怕几天后宿醉感消退了，身体各组织深处依然会留存这段酒精损伤的“生物学记忆”。无可辩驳的研究数据证实，长期频繁饮酒会损害大脑机能，甚至导致脑容量萎缩；正因如此，辛克莱尔彻底戒掉了过去每天喝一杯的习惯。罗根也讲述了自己对待酒精的态度转变。他曾彻底戒酒 8 个月，期间感受到了前所未有的精力与清爽；后来他在与妻子共进晚餐时喝了一杯玛格丽特鸡尾酒，虽然重新开始接触酒精，但他已经彻底告别了“喝醉”的状态。如今罗根一年多没有醉过酒，偶尔只在晚餐时品一杯红酒，或者在上台演出前抿一小口威士忌。对他而言，宿醉后的早晨去完成既定高强度体能训练简直是种酷刑；为了几小时的喧闹放纵，去牺牲一整天神清气爽、满怀激情的运动与生活状态，是极不划算的交易。辛克莱尔总结道，保持健康不该是一项沉重的苦差事，若是能将其变成一种爱好，生活活力就会成为从事任何智力或创造性事业的强大引擎。 - **大脑损伤数据**：持续、规律的饮酒会导致大脑结构变化，甚至造成可测量的脑容量萎缩。 - **饮酒习惯的转变**：辛克莱尔放弃了每日小酌；罗根戒酒 8 个月后恢复极低频次的微量浅尝，坚决不再把自己喝醉。 - **身心动力模型**：保持健康是在为身体打造“更大的油箱”与“更强劲的引擎”，体力与精力的充沛会直接反哺脑力与创造力。 --- ### [02:10:17](https://www.youtube.com/watch?v=hxid7FofhMw&t=7817s) 胶质淋巴系统、深度睡眠与穿戴设备的生理监测在探讨精力的来源时，话题转向了咖啡与睡眠。面对外界对咖啡因褒贬不一的评价，两人一致力挺咖啡，认为只要不过量摄入，适量饮用咖啡对健康有益。辛克莱尔进一步强调，比起单纯的睡眠总时长，高质高效的“深度睡眠”才是延缓衰老的核心关键。在深度睡眠期间，大脑的胶质淋巴系统（Glymphatic System）会全速运转，清理脑内堆积的毒素以及错误折叠的蛋白质；哪怕总睡眠时间较短，只要能保证约一个小时的高质量深度睡眠，第二天醒来大脑依然能够感到格外清晰和健康。 ```mermaid flowchart TD accTitle: 深度睡眠与穿戴式生理反馈监测回路 accDescr: 展示深度睡眠对大脑清理的生理机制，以及两款智能戒指与血糖仪构成的闭环数据监测系统。 subgraph SleepMech["深度睡眠机制"] A["进入深度睡眠状态"] --> B["胶质淋巴系统启动"] B --> C["清除错误折叠蛋白与代谢毒素"] C --> D["清晨清醒度与脑力修复"] end subgraph Wearables["穿戴设备多维度监测"] E["Oura Ring"] --> F["监测睡眠分期与深睡效率"] G["Ultrahuman Ring"] --> H["监测心脏健康与心血管年龄"] I["连续血糖仪 (CGM)"] --> J["实时监测饮食引起的血糖波动"] end subgraph DataFeedback["AI 数据整合与行为矫正"] F & H & J --> K["AI 算法实时洞察分析"] K --> L["改善睡眠习惯"] K --> M["戒除升糖垃圾食品"] K --> N["直观展现饮酒破坏睡眠的代价"] end ``` 罗根注意到辛克莱尔的手指上戴着两枚智能戒指，辛克莱尔笑称自己“两只手上都戴着，所以没一个读数是准的”。随后他认真解释了原因：较厚的一枚是 Oura Ring，以睡眠分期监测见长；较薄的一枚是 Ultrahuman Ring，主要用来追踪心血管年龄和心脏数据；同时他的手臂上还贴着连续动态血糖仪（CGM）。这些穿戴设备正结合 AI 技术提供即时反馈，例如分析昨夜哪一顿饭导致了血糖暴增。辛克莱尔透露，他曾让自己的儿子佩戴过一段时间血糖仪，孩子亲眼看到垃圾食品如何让体内血糖剧烈飙升后，便自觉在很长一段时间里远离了垃圾食品。罗根补充道，Oura 等设备的数据同样改变了许多人的饮酒观，因为用户能直接看到睡前哪怕仅喝两杯酒，整夜的睡眠架构也会被彻底破坏。 - **胶质淋巴系统（Glymphatic System）**：主要在深度睡眠期活跃，负责冲洗清除中枢神经系统中的代谢废物和错误折叠蛋白。 - **穿戴设备配置**： - **Oura Ring**：专门用于高精度追踪睡眠周期与深度睡眠效率（常年保持在 90% 以上效率）。 - **Ultrahuman Ring**：用于追踪心脏负荷及心血管年龄（Cardiac Age）。 - **连续动态血糖仪（CGM）**：实时监测体液葡萄糖浓度，直观呈现不同饮食结构引发的升糖峰值。 --- ### [02:13:37](https://www.youtube.com/watch?v=hxid7FofhMw&t=8017s) 睡眠卫生：从药物警惕到睡前降噪仪式围绕睡眠质量的优化，辛克莱尔提到了莫达非尼（Modafinil）等促智药物的副作用。他表示自己必须远离莫达非尼，罗根也赞同这种药物会对后续的睡眠造成严重干扰。辛克莱尔坦言，为了获得如今这种高效率的深度睡眠，他付出了巨大的努力来重建自己的作息。在过去的 50 年里，他始终处于“两头烧蜡烛”的透支状态，承受着极其严重的职业倦怠（burnout）；如今他通过科学的生活方式终于修正了这一恶性循环。现在的辛克莱尔在睡前拥有一套严格的降噪与放松仪式：在准备入睡的前几个小时将家里的灯光调暗，给大脑留出安静的缓冲时间，主动在脑海中冥想能让自己快乐和平静的场景，彻底将繁重的工作思绪隔绝在外。当被罗根问及是否会完全远离手机或佩戴防蓝光眼镜时，辛克莱尔坦承自己还没有完全做到彻底离开手机屏幕，此前也尝试过防蓝光眼镜但个人感受效果并不显著。随后，他向罗根抛出了一个鲜为人知的重要生物学事实：白天如果过度阻隔蓝光或者完全不见蓝光，同样会对人体产生意想不到的影响。 - **莫达非尼（Modafinil）的睡眠干扰**：两人一致认为该药物会严重破坏自然睡眠节律。 - **辛克莱尔的睡前准备**：提前数小时调暗室内照明，主动进行心理降噪，戒除长达 50 年的过度劳累恶习，将睡前注意力从工作转移到快乐平静的事物上。 ### [02:14:25](https://www.youtube.com/watch?v=hxid7FofhMw&t=8065s) 室内紫光缺失、近距离屏幕与视力退化 David Sinclair 提到日本有一位学者针对现代人近视（myopia）高发的现象提出了前沿假说。在动物实验中，缺乏感知紫光（violet light）能力的小鼠会患上近视，而现代人类长期身处室内，LED 人工光源与室内环境几乎彻底过滤掉了紫光波段。该学者甚至研发出一种可以在室内照射紫光的装置，并指出生活在乡村、经常到户外接触自然光谱的人群，配戴眼镜的需求明显更低。如果缺少紫光确实是导致现代人普遍近视的根源，那将是一项颠覆性的发现。 Joe Rogan 极为赞同这一逻辑，并结合切身体验指出人工光源和超近距离用眼的危害。当他疲惫地躺在黑暗的卧室刷手机时，屏幕光线会刺痛眼睛，而正常白天并不会如此敏感。现代职场人整天在不足三英尺的距离死盯电脑屏幕，随后又无缝切换到手机、平板或电视，眼部肌肉完全得不到喘息。Sinclair 进一步解释，人类眼球的生理结构本是为了远眺而设计的；当极目远眺时眼部肌肉是自然放松的，而强行聚焦在咫尺之遥的近处，睫状肌等肌肉必须持续紧绷数小时，最终因过度疲劳和老化失去调节能力，晶状体也会变得僵硬不灵活。 ```mermaid flowchart TD accTitle: 现代生活环境与近视及视力退化机制 accDescr: 展示室内 LED 缺乏紫光与近距离屏幕用眼如何共同导致晶状体硬化及视力下降。 subgraph 光谱与环境因素 A["长期身处室内环境"] --> B["LED 缺乏紫光 (Violet Light)"] B --> C["眼球缺乏特定光信号刺激"] end subgraph 肌肉与机械负荷 D["长期凝视近处 (手机/电脑)"] --> E["眼部肌肉持续收缩紧绷"] E --> F["睫状肌疲劳与晶状体弹性丧失"] end C --> G["近视加剧与视力老化"] F --> G ``` ### [02:16:37](https://www.youtube.com/watch?v=hxid7FofhMw&t=8197s) 87 岁父亲的抗衰奇迹与红光床建议 Sinclair 谈到自己 87 岁的父亲身体非常健康，但唯一出现衰退迹象的就是视力。Rogan 随即强烈建议他为父亲添置一张红光理疗床（red light bed），直言红光治疗是他个人尝试过的所有健康干预中见效最明显、影响最深远的项目。Sinclair 欣然采纳，并提到父亲当晚正从悉尼飞抵波士顿。 Sinclair 自豪地分享了父亲的生活状态：作为一位紧跟前沿科学的老人，他常年服用 NMN（烟酰胺单核苷酸）、白藜芦醇（resveratrol）和二甲双胍（metformin），每周坚持去健身房锻炼两到三次，还会进行长距离步行。在 Sinclair 的家族中原本存在寿命不长的遗传倾向，许多亲属在较年轻时就去世，父亲在六十多岁前也只是个普通人，甚至做好了活不过七十几岁的心理准备。但他随后主动掌控生命，在过去的二十年间，除了眼睛老化外，身体机能几乎没有岁月侵蚀的痕迹。两周前他还在日本旅行，举手投足、行动敏捷的程度宛如四十岁的中年人。 - Sinclair 父亲的抗老日常组合：NMN、白藜芦醇、二甲双胍、规律力量训练与徒步。 - 87 岁依然保持无慢性病、无酸痛的状态，全球跨国旅行毫无障碍。 ### [02:18:11](https://www.youtube.com/watch?v=hxid7FofhMw&t=8291s) 抗阻训练的重要性与健身赌约 Rogan 与 Sinclair 深入探讨了力量训练在衰老过程中的防御价值。抗阻训练不仅能够维持骨密度和肌肉量，更是防止跌倒的核心保障。老人如果肌肉充实、平衡感好，即便摔倒也只会“像皮球一样弹开”（"bounce"），而不会发生致命的骨折。Sinclair 坦言 87 岁的父亲在健身房的平衡能力和器械力量甚至强过自己，自嘲道这正说明自己有多虚弱。 Rogan 顺势督促 Sinclair 必须把力量训练提上日程，并当场定下约定：下次 Sinclair 再来录播客时必须练出一副强壮的体格。Rogan 承诺帮他在马萨诸塞州物色顶尖的私人教练，要求他每周雷打不动训练三天。Sinclair 开玩笑说，此刻可能有数百万听众在屏幕前大喊：“David，快回实验室去，别管什么健身房，赶紧做长寿研究！”但 Rogan 强调，力量训练能提升精力和专注力，只会让科研效率更高。两人还提到了 70 岁久坐老人与同龄马拉松跑者的肌肉组织 MRI 对比切片图，生动展示了不运动导致的肌内脂肪浸润和骨髓脂肪化，凸显了力量训练不可替代的生物学必要性。 ### [02:19:51](https://www.youtube.com/watch?v=hxid7FofhMw&t=8391s) 低氧与极端环境训练（Hypoxia Training）在谈及有氧运动时，Rogan 介绍了自己刚安装完成的一套低氧训练舱（hypoxia machine）。该设备能够精准模拟海拔 14,000 英尺（约 4,260 米）的高原低氧环境，并配备了可加热至 115 华氏度（约 46 摄氏度）的高温元件。在极度缺氧与酷热的双重夹击下运动，犹如“直通地狱”。这套训练系统由 Rogan 的好友、澳大利亚知名弓猎手 Adam Greentree 推荐，设备商朋友 Roman 亲自为其安装调试。该训练依托严密的心率监控协议，科学规划推力与间歇，对运动员心肺耐力的提升效果极其显著。Sinclair 从长寿生理机制分析，这正是经典的“激效反应”（hormesis）：人体在跳出舒适区、面对极端压力刺激时，会激活深层的细胞适应机制。 - 舱内模拟环境：海拔 14,000 英尺的氧分压，环境温度最高可达 115°F。 - 核心作用：通过可控的低氧刺激促进肌肉微血管生成与心肺机能代偿适应。 ### [02:21:20](https://www.youtube.com/watch?v=hxid7FofhMw&t=8480s) 高压氧舱的生理机制与视差欺骗对话延伸至以色列著名的长寿高压氧舱（Hyperbaric Oxygen Therapy, HBOT）研究。Rogan 透露自己不仅在以色列亲自体验过，家中也配置了一台高压氧舱，并且严格完成了经典的“90 天内进行 60 次、每次 90 分钟”的研究协议。该临床试验的数据极其坚实，证实该方案能加速伤口愈合、提升记忆力并显著延长端粒长度。 Sinclair 分享了他造访以色列研究团队时的一段轶事：当地研究人员曾开玩笑说他们使用的加压舱是德国制造的，这个涉及历史伤痛的黑色幽默让 Sinclair 颇感尴尬。不过，更关键的是其科学内核——以色列科学家与 Sinclair 的共识是：**真正带来血管新生等生物学收益的，并不是持续的高压高氧环境本身，而是从超高氧状态降回常态时，机体所感知到的“相对低氧伪影”**。这种相对落差激发了与低氧舱类似的代偿反应，诱导新生血管生长，其生理机制类似于伟哥（西地那非）等药物舒张血管的通道。Sinclair 提到他们在 2012 年发表的一篇论文中，也曾深入研究过能够调控微血管网络的补充剂分子。 ### [02:22:41](https://www.youtube.com/watch?v=hxid7FofhMw&t=8561s) 血液流动与衰老：NMN、运动与血管生成大卫·辛克莱（David Sinclair）指出，补充 NMN（烟酰胺单核苷酸）可以通过清除随着年龄增长而逐渐累积的特定有害蛋白质，促使动物体内重新生长出新生血管。从机制上讲，口服 NMN 药丸能够模拟甚至逆转血管退化的过程，而坚持体育锻炼同样能达到这种促进血管生成的效果。辛克莱强调，主流医学界极少深入探讨一个核心问题：人类步入老年后之所以百病缠身，最主要的原因之一正是“血流灌注不足”（lack of blood flow）。以血管性痴呆（vascular dementia）为例，它是全球第二大常见痴呆症类型，其根源就在于脑部血流不足。然而令人乐观的是，血流问题其实是所有衰老相关病症中最容易逆转的一项。要改善全身及大脑供血，最直接的方法就是保持锻炼，或者使用 PDE5 抑制剂（如万艾可/伟哥，Viagra），再或者补充 NMN 这类前沿抗衰分子。乔·罗根（Joe Rogan）随即插话表示，将这三者全部结合才是最理想的综合方案。辛克莱听后大笑坦言，自己目前已经做到了“三选二”，并且希望很快能把三者全部占齐。两人一致认为，保护大脑功能是延寿过程中最重要的防线，因为“又老又痴呆”是比任何身体疾病都更加糟糕的噩运，必须时刻牢记保持全身血液顺畅流动的决定性意义。 - **血管性痴呆的成因**：作为全球发病率第二高的痴呆类型，主要由于微循环与脑血管血供不足引发。 - **改善血流的三大干预途径**： - 坚持规律的有氧或耐力运动； - 临床使用 PDE5 抑制剂（如万艾可 / Viagra）促进血管扩张； - 补充 NMN 促进血管内皮细胞新生。 --- ### [02:23:47](https://www.youtube.com/watch?v=hxid7FofhMw&t=8627s) 结语与致谢：传播抗衰科学与支持前沿研究在对话尾声，乔·罗根对大卫·辛克莱的到访表达了由衷的感谢，盛赞他是科学界的“无价之宝”（a treasure），并感谢他不遗余力地向公众普及当今生命科学领域最前沿的突破。辛克莱对此十分感动，反过来向罗根致谢，赞扬罗根利用自身巨大的播客影响力向全世界传播严肃前沿的科研知识，认为罗根所做的事情给无数受众带来了不可估量的益处，简直是“在做功德无量的事”（literally doing God's work）。辛克莱承诺团队会全力以赴推进更多延缓衰老的突破性研究。节目结束前，罗根向听众推荐了辛克莱及其团队的研究与公益平台网站 lifespan.com，呼吁有能力和意愿的听众前往该网站进行捐赠支持，共同推动能够改变人类未来的抗衰老科学事业。最后，两人在热烈友好的氛围中互道珍重，圆满结束了本次对谈。 ## Notable quotes > [01:31:27](https://www.youtube.com/watch?v=hxid7FofhMw&t=5487s) 我们现在不会直接啃树皮了 — David Sinclair > [01:41:00](https://www.youtube.com/watch?v=hxid7FofhMw&t=6060s) 去你的基因（the FU gene） — David Sinclair > [01:42:57](https://www.youtube.com/watch?v=hxid7FofhMw&t=6177s) 父母应扮演导师而非发号施令的独裁暴君 — Joe Rogan > [01:57:02](https://www.youtube.com/watch?v=hxid7FofhMw&t=7022s) 遗忘了细胞身份 — David Sinclair > [01:57:59](https://www.youtube.com/watch?v=hxid7FofhMw&t=7079s) 千万不要把我彻底变回婴儿 — David Sinclair > [02:01:08](https://www.youtube.com/watch?v=hxid7FofhMw&t=7268s) 生命太短暂了，让我们来解决它（Life's too short. Let's fix that.） — David Sinclair > [02:18:11](https://www.youtube.com/watch?v=hxid7FofhMw&t=8291s) 活力反弹（bounce） — Joe Rogan > [02:19:51](https://www.youtube.com/watch?v=hxid7FofhMw&t=8391s) 相对低氧伪影 — David Sinclair > [02:23:47](https://www.youtube.com/watch?v=hxid7FofhMw&t=8627s) 这简直是在做上帝的工作（literally doing God's work） — David Sinclair ## Mentioned 大卫·辛克莱尔（David Sinclair）, 乔·罗根（Joe Rogan）, 杰夫·贝索斯（Jeff Bezos）, 山姆·奥特曼（Sam Altman）, 布莱恩·阿姆斯特朗（Brian Armstrong）, 山中伸弥（Shinya Yamanaka）, 亚历克斯·扎沃龙科夫（Alex Zhavoronkov）, 安妮·雅各布森（Annie Jacobsen）, 加里·布雷卡（Gary Brecka）, 亚当·格林特里（Adam Greentree）, Life Biosciences, Altos Labs, Retro Biosciences, NewLimit, ATAI Life Sciences, Neuralink, 英矽智能（Insilico Medicine）, Perplexity AI, Joovv, Pure Encapsulations, Oura Ring, Ultrahuman Ring, 《国家地理》（National Geographic）, 《Lifespan》, ER-100, (±)-JRT, NMN, 白藜芦醇（Resveratrol）, 二甲双胍（Metformin）, 莫达非尼（Modafinil）, 伟哥（Viagra） ## Video description David Sinclair, AO, PhD, is a longevity scientist, Professor of Genetics at Harvard Medical School, author of the book "Lifespan: Why We Age—and Why We Don't Have To," and host of the "Lifespan" podcast. https://www.youtube.com/c/davidsinclairpodcast https://www.simonandschuster.com/books/Lifespan/David-Sinclair/9781501191978 https://lifespan.com https://davidasinclair.com Perplexity: Download the app or ask Perplexity anything at https://pplx.ai/rogan. Visit https://superpower.com/rogan for $20 off your membership. This video is sponsored by BetterHelp. Visit https://BetterHelp.com/JRE [Source](https://www.youtube.com/watch?v=hxid7FofhMw)

Source quotes

[91:27] David Sinclair: 我们现在不会直接啃树皮了 [101:00] David Sinclair: 去你的基因（the FU gene） [102:57] Joe Rogan: 父母应扮演导师而非发号施令的独裁暴君 [117:02] David Sinclair: 遗忘了细胞身份 [117:59] David Sinclair: 千万不要把我彻底变回婴儿 [121:08] David Sinclair: 生命太短暂了，让我们来解决它（Life's too short. Let's fix that.） [138:11] Joe Rogan: 活力反弹（bounce） [139:51] David Sinclair: 相对低氧伪影 [143:47] David Sinclair: 这简直是在做上帝的工作（literally doing God's work）

Source quotes

[91:38] David Sinclair: It's almost the same molecule as LSD, but scientists swapped the positions of just two atoms in the structure. The subtle change makes JRT bind more selectively to serotonin receptors in a way that promotes neuroplasticity... but minimizes hallucinogenic signaling. [96:00] David Sinclair: I call this the FU gene because I'm trying to figure out what makes humans special over other animals... It turns out that this gene is turned on in teenagers... It's a way genetically to get them out of the nest. [120:14] David Sinclair: Life's too short. Let's fix that.

Original transcript

[0:01] Joe Rogan podcast. Check it out. [0:03] >> The Joe Rogan Experience. [0:06] >> TRAIN BY DAY. JOE ROGAN PODCAST BY [0:08] NIGHT. All day. [0:12] >> Mr. Sinclair. Good to see you again. [0:16] >> Dr. Sinclair. [0:16] >> Doctor. [0:17] >> I'm kidding. It's better that way, [0:18] right? [0:19] >> Yeah. Do you ever introduce yourself as [0:21] doctor? [0:21] >> Never. [0:22] >> Yeah. That's a kind of a It's a weird [0:24] thing because you're allowed to. [0:26] >> I'm actually a Sir David from Australia, [0:28] but [0:28] >> Are you a sir? Yeah, but I I it's kind [0:30] of a joke. I don't really [0:31] >> What does that How's that work out? Did [0:33] you geted or representative gave me some [0:37] Australian version of a nighthood? [0:39] >> But uh it I get to put AO at the end of [0:42] my name. [0:43] >> AO? [0:44] >> Yeah. Order of Australia. [0:45] >> Oh, [0:46] >> but it actually makes no difference to [0:48] my life. So, it's just an extra couple [0:50] of letters. [0:50] >> It's kind of cool. [0:52] >> I'm honored for sure, but uh it uh it's [0:57] just a joke. You don't know. [0:58] >> Well, it's kind of anybody, sir. You [1:00] meet a guy at the gas station. How you [1:02] doing, sir? [1:03] >> It's like, wow, how does he know? [1:05] >> Right. You don't say, "How you doing, [1:07] king?" [1:08] >> Yeah. [1:08] >> Right. [1:09] >> Well, I'm David. I'm Australian. So, in [1:11] Australia, if you have any ego, you get [1:13] beaten up in the playground. So, [1:15] >> that is true. Australia is the land of [1:17] the tall poppy syndrome. They don't They [1:19] don't [ __ ] around. They don't like you [1:21] getting a big head in Australia. [1:23] >> That is That is true. Um, I like to go [1:25] back there, though, because it's an a [1:26] level playing field. Nobody cares who [1:28] you are. [1:29] >> I love the people there. The Australian [1:31] people are some of my favorite people. [1:32] They're awesome. They're just They're [1:34] very friendly and fun. [1:36] >> It's a great place to be. It's just too [1:38] far to get there. Such a hall. [1:40] >> Oh, no. If you just, you know, whiskey [1:42] in an ambian and you're there without [1:43] >> Is that what you do? [1:44] >> I used to. I've gone clean. I don't [1:47] drink much at all anymore. Last time. [1:49] >> What does that mean? How often is drink [1:50] much at all? [1:51] >> Uh, celebration. [1:52] >> You want to drink right now? [1:53] >> Uh, no. It would be a bad look. [1:55] [laughter] I've got the coffee that you [1:57] gave me, which [1:57] >> Yeah, this is a layered superfood [1:59] coffee. So, layered Hamilton. He has c [2:02] it's black rifle coffee mixed with his [2:05] superfood stuff, which is um this one's [2:07] turmeric. So, it's turmeric and I think [2:09] it has coconut milk in it and some other [2:12] jazz. It's great. Delicious. [2:13] >> Anti-inflammatory, too. [2:14] >> Yes, they've done [2:16] >> which I know you're all about. [2:17] >> Uh yes. As a a profit of longevity. [2:22] >> Yes. Is that [laughter] is that another [2:24] title of you? [2:25] >> Yes, you can call me Sir David the [2:26] prophet. How about that? [laughter] [2:29] >> Sir David the prophet. Dr. Sir David the [2:32] prophet of longevity. [2:33] >> That'll do. [2:33] >> Um, so there's a lot. Let's just jump [2:36] right into it because there is a lot [2:38] going on in the longevity space. [2:40] >> Thank you for having me back on. It's my [2:41] pleasure. And by the way, I also want to [2:43] thank you [2:44] >> uh for I think this is the fourth time [2:46] on which is amazing. Thank you. Congrats [2:49] on all your success. It's wonderful to [2:51] see. Um, also the the book that I wrote, [2:54] which you first had me on to promote, [2:56] has done so well and it's really because [2:57] of you and the book Lifespan uh became a [3:00] bestseller. Not not just that, but it's [3:02] now been read millions of times around [3:04] the world. It's in 40. [3:05] >> Well, that's phenomenal and it's my [3:06] pleasure. [3:07] >> And that's not a promo. As you know, you [3:09] don't make any money from books really, [3:10] but I'm just honored that uh it was read [3:13] by so many people around the world [3:14] because it wasn't an easy read. It was [3:16] high high-tech science. Well, people are [3:19] very interested, especially nowadays. [3:21] It's uh I think I've never I I can't [3:24] recall a time in my life where [3:28] optimizing your health and longevity has [3:32] been more of a subject that people are [3:33] interested in. [3:34] >> Well, I think that's largely because not [3:36] to keep blowing smoke in up your uh [3:39] rear, but largely because of what you [3:41] did and the book. So the book went [3:43] global and it's it was right in 2019 and [3:48] the pandemic hit and I think most people [3:50] saw their own mortality at that point. [3:53] Most people under the age of about 70 [3:55] didn't even think about dying but then [3:57] pandemics like [ __ ] I could die and uh I [4:00] saw the book take off. You launched it. [4:02] Um but yeah since then a lot of people [4:04] have jumped on the bandwagon and now [4:06] longevity is I hear this everywhere I [4:08] go. [4:08] >> It's everything. It's everywhere. People [4:10] are constantly talking about different [4:12] modalities. How often do you cold [4:14] plunge? Are you sauna? What about the [4:16] red light? And what do you think? Is [4:17] this legit? Is that legit? Like there's [4:19] everybody's optimizing everything [4:21] constantly all the time. But the reason [4:23] why it's caught on is cuz if you do [4:25] follow some of the protocols, you will [4:27] feel better. And so that's the ultimate [4:30] goal. Like longevity is wonderful, but [4:32] feeling better in the moment currently [4:34] like living your life should be primary. [4:37] Longevity I think is uh [4:40] If you're optimizing your life and you [4:43] feel better, you will live longer. It's [4:45] like this, it's all part of it. [4:47] >> Would follow the longevity principles [4:49] and the ideas behind it, you you [4:51] certainly will live better right now. [4:53] >> You will. And it's not even that hard. [4:54] There are [4:55] >> basic things, five basic things you can [4:57] do or avoid [4:58] >> and you can live another 15 years. It's [5:00] really not that hard. And that's what [5:01] I'm excited about telling millions of [5:03] people today is and maybe we can go over [5:05] the kind of things that people can do [5:06] easily to live longer. Well, I want I [5:08] definitely want to do that, but I I also [5:10] want to talk about like what what is the [5:12] current state of science uh as applied [5:16] to longevity treatments? Like because I [5:19] know that there's some pretty [5:21] groundbreaking stuff that's in the [5:23] pipeline right now. Yeah, it's so since [5:26] 2019, [5:28] a lot of what we talked about has come [5:30] true, which is the amazing thing. [5:32] >> [clears throat] [5:32] >> We uh were speculating 2019 that we [5:36] could potentially reverse aging and that [5:38] was a sin to say that as a scientist [5:41] publicly in those days. I put it in the [5:43] book. Um and it it's actually come true [5:46] since then. Uh certainly for the lab uh [5:49] for mice, monkeys and now we have a [5:52] human clinical trial. The first [5:54] potential human age reversal technology [5:56] is in people right now. Listen, it [5:58] completely seems logical. The idea that [6:01] that at one point in time would have [6:02] been heresy in science to discuss it. So [6:06] that seems crazy like if we if people [6:09] get old and we understand the mechanism, [6:11] why couldn't we reverse it? [6:13] >> Well, I think for a long time we had to [6:14] accept it um in the way that cancer used [6:17] to be accepted 200 years ago probably [6:19] that there was nothing you could do [6:20] about it. And then my colleagues and I [6:22] found that aging has a root cause that's [6:24] the same in pretty much every cell in [6:26] the body and that we could control that [6:28] and that there were genes that not only [6:30] slowed it down but in 2020 we had a big [6:33] publication that showed we could [6:34] actually safely for the first time [6:35] reverse that process like reinstalling [6:38] software in the cell to make it work [6:40] again. [6:41] And so what is the pro is that using [6:43] crisper? Like what what are you using to [6:46] >> Well, we we deliver genes into the body [6:48] like crisper. Uh I have a little little [6:52] prop here I brought in my pocket here. [6:54] Uh this is a representation of how we [6:56] deliver the age reversal genes. It's a [6:58] virus-like capsule that we make in the [7:01] lab. [7:02] >> And this is what's going into the [7:03] patients right now into their eyes. [7:06] Initially [7:08] >> uh and the eye is a good place to start. [7:10] How do you pick the people to get on [7:12] these tests? [7:12] >> They they volunteer. Um I was really [7:16] fortunate uh to see the first patient [7:19] get dosed earlier this year. Um and that [7:23] person bravely volunteered to be the [7:25] first person to get trillions of these [7:28] injected into his eye to see if it could [7:30] could cure his glaucoma loss of vision. [7:34] >> I bet if you have glaucoma, you're [7:35] probably like, "Listen, what's the worst [7:37] that can happen?" [7:38] >> Well, exactly. He pretty much was [7:40] totally blind in one eye and so there's [7:42] really nothing that he has to lose. [7:45] There's a risk that something might go [7:46] wrong, but not really. He uh the good [7:51] news is and I can report to everybody [7:53] around the world that nothing's gone [7:55] wrong so far. Everything's proceeding [7:58] according to plan and we're at a turning [8:01] point potentially in human history if it [8:03] works. So, I I interrupted you, but [8:05] explain this little virus truck. [8:08] >> Sure. And for those of you listening, [8:10] I've got a little rubber ball with [8:11] spikes on it. It looks a bit like CO, [8:12] but don't be scared of it. It's not a [8:15] pathogenic uh virus. It's actually a [8:17] domesticated version of a virus. And [8:19] this little plastic ball has little [8:22] adapters. These red balls on the surface [8:24] of the big ball uh target it to the [8:27] cells in the back of the eye. And you [8:28] can change the balls to target different [8:30] tissues. We could change that outside [8:32] little spike and target it to the liver, [8:34] which we've done and cured mice of their [8:36] fatty liver disease as well. But this [8:38] one's for the eye. And within that big [8:41] ball is a protein capsule. And inside [8:44] the protein capsule is our DNA special [8:48] delivery, which we call OSK or O ER 100. [8:53] Er is epigenetic reprogramming 100. the [8:56] drug that we know when we put it into [8:58] human cells, it makes them younger and [9:01] then they work like they were young [9:02] again. [9:05] This sounds like the beginning of a [9:06] horror movie. [laughter] [9:08] >> You know what I mean? Like the scientist [9:09] is on a talk show and the scientist is [9:12] explaining it and everyone's at home [9:14] like with their coffee like, "Wow, we're [9:17] this is wonderful. We're going to get [9:19] younger again. Don't worry, it's all [9:21] going to work out." 28 days later, [9:23] garbage in the streets, [snorts] cars on [9:25] fire, the guy's waking up from a coma, [9:28] doesn't know what happened, [9:29] >> goes outside, these optimized humans are [9:31] eating each other. [9:32] >> I admit [laughter] I admit it is science [9:34] fiction and I even have to pinch myself [9:36] that it's actually happening. But we've [9:38] done a lot of safety studies and this [9:39] trial is FDA approved because they've [9:41] looked at all the data. [9:42] >> Well, God knows they never [ __ ] anything [9:44] up. [laughter] [9:44] >> Yeah, I figured you might say that, too. [9:46] >> Perfect. [9:47] >> Yeah. Well, it's in the eye. So, that's [9:49] why we start with the eye. It's [9:50] enclosed. It's not going to spread. [9:53] Nobody's going to grow another eye. [9:54] >> And so these trillions of cells that [9:58] you're putting into the eyes, [10:00] >> the little capsule, the virus like [10:02] >> trillions, I shouldn't call them cells. [10:04] Twillions of capsules that you're [10:06] putting into the eye. What What are they [10:09] doing for glaucoma? [10:12] >> Well, what they're doing is there are [10:13] three genes in this DNA [10:16] uh package and I called them OSK. [10:19] OSK are three special genes that we [10:23] found safely reprogram cells and reboot [10:26] the backup copy of youth which we now [10:28] believe exists in our body. That's a big [10:31] deal that there's a backup copy of [10:33] youth. Even an old person, I don't see [10:35] that an old person anymore on the [10:36] street. I just see a person that needs [10:38] to be rebooted. These OSK genes [10:41] >> you just see Wait a minute. Hold on. [10:43] [laughter] [10:44] When you see old people, you don't see [10:45] old people. Do you think you just say, [10:47] "Oh, that poor po person needs to be [10:49] rebooted." [10:49] >> Yeah, [10:50] >> you're doing the perfect job for you. [10:52] Like your personality is perfectly [10:54] suited for your occupation if that's how [10:56] you actually look at people. [10:58] >> Well, I I do. And the reason is that we [11:01] [laughter] we all we all have this [11:04] backup copy that the DNA, the [11:07] instructions to be young that made us [11:09] into who we are as kids is still in our [11:11] bodies almost largely intact. [11:14] You just need to read it again. And [11:17] that's why reinstalling software or I [11:19] used to use the analogy of a CD. [11:22] Kids these days probably don't know what [11:24] a CD is. It's a it's a little plastic [11:26] circle like a record that we used to put [11:28] 20 songs on. It was awesome at the time. [11:30] >> I think most people know. [11:31] >> I'm kidding. I'm kidding. It's a bit of [11:32] a a silly joke. [11:33] >> Maybe a 10-year-old does. [11:34] >> When I when I teach kids at Harvard, [11:36] most of them have never held a CD. So, [11:38] >> isn't that wild? [11:40] >> Yeah. Uh though they they're not coming [11:42] back, but albums definitely. So think of [11:44] it like an album that you scratch and [11:46] the scratches are like aging and we are [11:49] getting rid of the scratches with the [11:51] these three genes OSK. So let let me [11:53] tell you how these three genes work. We [11:55] found [11:56] >> uh there was a person uh whose name uh [11:58] is well known in science circles called [12:00] Shina Yamanaka from Japan obviously and [12:04] he discovered that there was a set of [12:06] four genes that could reliably make [12:09] adult cells like skin cells uh into stem [12:12] cells and he deservedly won the Nobel [12:15] Prize for that in 2006. [12:17] But that wouldn't be useful here. We if [12:19] I turned you into a bunch of stem cells [12:22] you'd probably die within a few minutes. [12:24] So we don't want to do that and cancer [12:26] is also a potential. So it took us about [12:29] well from 2019 it took us a while to [12:33] figure out that if we leave out one of [12:35] the aminaka genes and just use three OSK [12:38] leave out the other one called M we get [12:41] safe age reversal about 75 80% back to [12:44] youth but no further. We don't go back [12:46] to zero which is what Yamanaka did. And [12:49] instead of cells losing their identity, [12:50] which is what a stem cell has no [12:52] identity, we regain identity. So it's [12:55] actually I could draw graphs, but it [12:57] doesn't really help listeners. But [12:58] basically, old old age is losing [13:01] identity of your cells. So they don't [13:02] work. They forget how to work. That's [13:04] what we think old age is in my lab. And [13:06] stem cells have no identity. It was like [13:08] a a very early embryo. In between, we [13:11] our cells have a lot of identity. They [13:13] function beautifully. We're in our 20s. [13:15] We're at peak. And what we've done is [13:18] we've figured out how to go back towards [13:21] youth, get these cells to work like they [13:23] did again back get the backup copy [13:26] somewhere exists. We're looking for it. [13:28] Uh and now cells actually behave like [13:30] they did when we were 20. And if it [13:33] works, we're going to have glaucoma [13:34] patients seeing for the first time. And [13:36] that's the beginning of a whole cascade [13:38] of drugs that I want to develop for [13:41] diseases of aging and eventually whole [13:43] body rejuvenation. [13:44] So the initial experiments are on [13:47] glaucoma because it's a contained thing. [13:49] The eyeball is a contained thing and you [13:52] could do it that way. [13:53] >> Yeah. My student Wanglu who was doing [13:55] this in 2017 I said let's do the liver. [13:58] Let's rejuvenate the liver and he said [14:00] no the eye is a good idea and he was [14:01] right. So that's exactly why we chose [14:03] that first. [14:04] >> But just think about how many people [14:06] have vision problems. [14:07] >> It's 40 million uh just in the US for [14:09] glaucoma. Macular degeneration is even [14:12] more. And in the lab we can cure that as [14:15] well in the mice. [14:16] >> Now macular degeneration and glaucoma [14:19] these are diseases of aging right you [14:22] would say or gluccom is a disease. [14:25] >> Oh yeah. [14:25] >> What about people that have had eyeball [14:27] injuries and things like is there a [14:30] backup copy of the eyeball where you [14:32] could sort of reformat the eyeball [14:34] structure? [14:35] >> You should come work in my lab. At least [14:37] come visit. Uh [14:38] >> I would love to visit. [14:39] >> And the reason I say that is that's the [14:40] exact question that we're asking. M [14:42] >> we showed that even if you injure say a [14:45] nerve uh whether it's peripheral on in [14:48] your arm or in your brain or in the eye [14:51] like the optic nerve we can regrow those [14:54] back to where they were and actually in [14:56] 2020 on the cover of Nature magazine [14:59] there was the picture of an eye and in [15:01] the in the paper we published you could [15:03] see the nerves regrowing back um and so [15:07] we we think that injury is also [15:09] treatable actually a group in China just [15:11] took our technology, this OSK stuff, put [15:14] it into mice that had bad joints and it [15:16] regrrew their muscle and their bone back [15:18] to normal. [15:19] >> Wow. [15:20] >> And so we we're also looking at treating [15:23] injury, back injury, joints, [15:25] osteoarthritis. [15:27] >> That would be phenomenal [15:30] because there's so many people that are [15:32] suffering from arthritis and so many I [15:34] know so many people with injuries like [15:36] martial arts injuries. I have one. My my [15:38] left knee is [ __ ] up. [15:40] >> It's it's annoying. I keep it together. [15:41] I'm got I've got it like m I maintain [15:44] it, but it's always an issue. I have to [15:46] stay on it. I [15:47] >> And there's little you can do like stem [15:49] cells a little bit of relief, but not [15:51] much. [15:51] >> Stem cells give you relief. Um but not [15:54] when once you're dealing with cartilage [15:56] damage and you're dealing with a I had a [15:58] meniscus surgery where they took out a [16:00] piece of my meniscus and I had my ACL [16:03] reconstructed on that knee as well. So, [16:05] it's it's just an issue, but it works [16:07] pretty good for like what it should be. [16:09] Like if we were living in the 1930s, I'd [16:11] be a [ __ ] [16:13] >> you know? [16:13] >> Well, hang in there because we're going [16:15] to be in a world where you we can [16:16] rebuild parts of the body, including [16:18] joints. [16:19] >> The problem with that is like, how does [16:21] that apply to athletics? We're going to [16:23] have [ __ ] super soldiers in every [16:26] sport. There's going to be people in [16:27] every sport that could do what Michael [16:29] Jordan did and like leap from halfway [16:30] across the basketball court and dunk. [16:33] >> That's that's probably coming. And there [16:35] may be DNA tests to see if you've got [16:37] these OSK genes inserted. Um, and we're [16:40] working on it. Working on a drink and a [16:41] pill as well for [16:42] >> a drink and a pill. [16:44] >> Yeah, we're I mean we're now eight years [16:45] ahead of what the public realizes. [16:48] >> Really? [16:48] >> In my lab at Harvard. Yeah. [16:50] >> A drink and a pill. And what's a drink [16:51] and a pill going to do? [16:53] >> Well, right now it's in mice. So, we've [16:55] still got a ways to go. But when we give [16:58] the drink to mice, they get rejuvenated. [17:00] >> You just give it to 80-year-olds. If [17:03] you're on the way out, like, let's [17:04] [ __ ] go. Like, give what the FDA is [17:07] for. They forbid that. Uh yeah, that's [17:09] what we need to get rid of them. Get rid [17:10] of the FDA and just give it to old [17:12] people. [17:13] >> If I was an old guy and I was like [17:16] hanging in there and I'm walking around [17:18] with and you're like, look, this drink [17:21] and a pill might kill you or you might [17:24] be like a 30-year-old again. I'm like, [17:25] let's [ __ ] go. [17:27] >> Well, I get emails a lot. I've had to [17:29] take my emails off public access cuz [17:31] there's a lot of people that that want [17:33] this. [17:33] >> Oh, I'm sure. There there was one guy [17:35] that wouldn't leave uh the building [17:37] until he saw me. So, it's getting to [17:39] that point. [17:40] >> Yeah, there's a little bit of that, [17:41] right? People get a little selfish, like [17:43] it's all about them. [17:44] >> Yeah. And actually, the US uh government [17:46] blocked an investment from a foreign [17:48] country into one of my companies cuz [17:50] they were afraid of super soldiers. [17:53] >> Ooh. What country? [17:54] >> Well, they're they were afraid of [17:55] technology getting out. Uh which which [17:58] country? [17:58] >> Could I guess? [18:00] >> Sure. [18:00] >> China. [18:01] >> It wasn't. Was it? [18:03] >> No. Russia, [18:04] >> it was somewhere in between here and [18:05] China, but I shouldn't say it's kind of [18:07] vague. [18:08] >> It's a little uh it's a little [18:10] sensitive. Uh but yeah, the US [18:12] government does have the ability to [18:13] block it foreign investment and they did [18:15] in this case. 160 million bucks they [18:17] blocked. [18:17] >> Wow. [18:18] >> That was a painful episode. [18:20] >> So they were worried that people were [18:21] going to actually engineer super [18:23] soldiers. This episode is brought to you [18:25] by Superpower. Your doctor spends eight [18:27] minutes with you and your insurance [18:29] company decides what blood work you're [18:31] allowed to get. That's not health care. [18:34] It's a broken system. With Superpower, [18:36] you have control over your health. For [18:39] $199, [18:42] you get all the tools you need to [18:44] understand your body. It starts with one [18:47] blood test measuring over 100 [18:49] biomarkers. Then they give you detailed [18:52] insights and a personalized plan built [18:55] around you, your labs, health history, [18:58] genetics, wearable data, and goals. Go [19:01] to superpower.com/rogan [19:05] and take control of your health. [19:07] >> Yeah. That this technology could give an [19:09] advantage. [19:10] >> The Russian experiments that they did [19:12] during World War II where they were [19:14] trying to come up with a chimpanzeee [19:15] human hybrid. [19:17] >> Tell us. [19:18] >> Yes. So, uh, it's very difficult [19:21] obviously to get information out of the [19:23] former Soviet Union as to what their top [19:25] secret programs were, but there seems to [19:28] be an indication that there was actual [19:29] real research to try to, you know, [19:32] because obviously Russia lost an [19:34] incredible amount of people in World War [19:37] II. I mean, tens of millions of soldiers [19:40] died in World War II from Russia. And I [19:42] think they said, "Wouldn't it be great [19:45] if it wasn't people?" And so they were [19:47] doing experiments with hybridization and [19:50] they were trying to combine human beings [19:52] and chimpanzees to create a you know a [19:56] stable of super soldiers that were like [20:00] some hybrid hominin. [20:02] >> Yeah. There's a scientist in New York [20:03] who does this for a living. [20:05] >> What he does that for [20:06] >> he's not creating them but he I've seen [20:08] uh I was on stage with him. He made uh [20:10] hybrid embryos. they didn't reach. [20:14] >> See, the thing is, if that guy's doing [20:16] that and he's ethical and he lives in [20:17] America and we have rules and [20:19] regulations and the FDA and all that [20:20] good stuff, what the [ __ ] is going on in [20:22] other countries where they don't have [20:24] that, [20:24] >> right? Right. Well, there's genetic [20:26] engineering of humans already. Um, and [20:28] certainly selection. Even even parents [20:30] today in the US can if they have the [20:32] money, they can select. [20:33] >> Well, people select [20:34] >> even based on people select for hotness. [20:37] >> They select for tallness. They select [20:39] for intelligence. [20:40] >> It's like Gatkov. Yes. It's a great [20:42] movie if you haven't seen it. [20:43] >> It is a great movie. Yeah. Um, so see if [20:46] you could find that Russian [20:47] hybridization program. It's uh it never [20:50] happened. I don't think I don't think [20:52] they did it, [20:53] >> but there's uh there's actually a guy [20:56] who was also involved in a gigantic [20:59] fertility scam. Not a not a scam per se, [21:03] but he was a doctor that was uh supposed [21:06] to be doing fertility treatments with [21:07] women. Like, you know, like if you went [21:09] with your wife to a doctor and said, [21:12] "Hey, we're having a hard time getting [21:13] pregnant and well, David, I just need [21:16] some of your sperm and I'll take your [21:17] wife's egg. We'll make you a nice baby." [21:19] And he was using his sperm on everybody [21:21] on everybody. Everybody gets mine. [21:24] >> One of my [laughter] kids partners is [21:27] from someone in the US who had hundreds [21:29] of babies. [21:30] >> Dude, there is a ton of those guys. As I [21:32] was doing research for this, [21:34] >> um, I started looking up all these [21:36] stories and I said, "Wait, this is a [21:37] different story. the same thing. There's [21:38] been a ton of these doctors from [21:40] fertility clinics that use their own [21:42] sperm. Just insane. But this one doctor [21:44] that did that also claimed that he [21:47] impregnated an orangutang. [21:50] >> Yeah. Like how how'd you do that? Uh [21:52] Soviet doctor Joseph Stalin. [21:55] >> Dictator. Oh, [laughter] [21:58] obviously wanted to rebuild the Red Army [22:00] in the mid1 1920s with Planet of the Ape [22:02] style troops by crossing humans with [22:04] apes. Stalin is said to have told even [22:06] off, "I want a new invincible human [22:09] being, insensitive to pain, resistant [22:10] and indifferent about the quality of the [22:12] food they ate." [laughter] Which is [22:14] crazy. The only legitimate source of the [22:16] claim comes from a 2002 paper in the [22:18] academic journal Science in Context by [22:22] the Russian historian of science, uh, [22:24] Kariel Ranov. [22:27] Rasianov's uh study follows the ill- [22:30] fated attempt by the Russian [22:31] psychologist or physiologist rather uh [22:34] that that word Ilia Evanov to crossbreed [22:37] humans with anthropoid apes. His [22:40] research offers an important warning [22:42] about the ethical abuses. [22:44] Did you do it? What happened? Um the [22:48] alleged quote from Stalin is not found [22:50] in the paper and there's no evidence of [22:51] Stalin ever uh ever made such a [22:53] statement. [22:55] >> Yeah, I don't know. [22:58] Uh, however, why the Soviets would find [23:01] such a human chimp hybridization program [23:03] in the first place and what could be [23:05] learned from this sor tale of ethical [23:07] misconduct is an important topic and [23:09] fascinating in its own right. It's a [23:11] that's an interesting way of phrasing it [23:13] like a sor tale of ethical misconduct. [23:15] Like, however, if you are going to go to [23:20] war, would you rather have like [23:23] humanmade orcs fight for us or, you [23:27] know, [23:29] Johnny Robinson who grew up down the [23:31] street who's a nice kid, right, who, you [23:33] know, just really wanted money for [23:34] college and so he signed up for military [23:37] service and you're going to fly him over [23:39] to fight this war that maybe he doesn't [23:41] need to die in when you can have these [23:43] monsters that you made in a lab fight? [23:45] Yep. And and the average ape can kill a [23:47] human with one punch. So, they're much [23:50] stronger than we realize. [23:51] >> That's what I'm talking about. Let's go. [23:52] >> Well, we're we're in the process of [23:54] building uh you know, anthropoid robots [23:56] that I think will be recruited to the [23:58] army. [23:59] >> Yeah, that's going to be weird. Like, [24:01] our robots beat your robots, so give us [24:03] your oil. How's that going to work? [24:04] >> And if we all have one at home, what [24:06] stops the government recruiting them [24:07] all? [24:07] >> Right. And also, what's the the real [24:10] problem's going to be we we both know [24:12] the real problem is going to be sex [24:13] robots. [24:15] is a problem. [24:16] >> It's going to be a problem for people [24:18] that don't have a sex robot. [24:19] >> They won't leave home. [24:20] >> It's going to be a problem with people [24:21] that want a regular person and there's [24:24] none available because everybody's got a [24:25] sex robot. [24:26] >> Yeah. That well comes with fewer strings [24:28] attached. [24:29] >> It also comes with the same problems [24:31] that AI comes with, right? Where AI [24:33] says, "David, you're amazing. Everything [24:35] you do is wonderful. You should be so [24:37] proud of yourself." No real. We would [24:40] all love that, but that's not healthy, [24:43] right? You're so big. [24:44] >> This is one of the re [laughter] This is [24:46] one of the reasons why rel actual real [24:48] relationships between human beings are [24:50] good is because you do things that are [24:51] annoying. You don't realize they're [24:52] annoying and then your wife or your [24:54] husband or whatever it is tells you, [24:57] "Hey, you're [ __ ] annoying." Like, [24:58] and you're like, "I'm sorry. I'll I'll [25:01] fix that. I didn't mean to. I didn't. [25:03] That's not what I was trying to do. I [25:05] was in my own head. I was thinking about [25:06] myself. You're right. I was selfish." [25:07] You get better. You It's like help [25:09] people grow. Like relationships are [25:11] important to help people grow. Not with [25:12] AI. Like, you can fart in my face any [25:15] day, David. I don't mind at all. Your [25:18] farts are amazing. [25:19] >> You know, the problem is they're going [25:20] to be way smarter than us, too. [25:22] >> Right. [25:23] >> I don't know how people are going to [25:24] say, "Go stack the dishwasher to to one [25:26] of these robots." You know, they're [25:27] smarter than all humans combined. [25:28] >> Yeah. But they're not going to mind [25:29] stacking. They're smart enough to [25:31] >> bought out of hell and they're going to [25:32] beat us up. [25:33] >> They don't care. They They're not going [25:34] to mind doing like menial tasks. But [25:37] while they're you're doing it, you know, [25:39] you can go explain to me [25:43] quantum entanglement. Like [laughter] so [25:45] while they're filling up the dishwasher, [25:48] >> they can go f you one day. [25:49] >> Well, if you have a particle and the [25:51] particles in [laughter] [25:53] >> Yeah. I just invented a cure for aging, [25:56] >> right? Well, look at what it's done with [25:57] mathematics. like just over the last [26:01] couple weeks they've solved more than 50 [26:04] program or 50 mathematical equations [26:06] that they have struggled for decade upon [26:09] decade to try to solve and AI is like oh [26:12] I got it. [26:13] >> Yeah. Well, biology is a little bit more [26:15] complicated but already AI is doing a [26:17] lot of the science that we used to do in [26:19] my lab. Uh in fact what we just recently [26:21] did it in a couple of months would have [26:23] taken about 160 years to complete. [26:26] >> What [26:26] >> and it's only getting faster. Eventually [26:27] someone came and make a drug on their [26:29] phone. [26:29] >> Say that again. [26:30] >> 2 months instead of 160 years. [26:33] >> Well, what exactly was it that you had [26:35] to do? [26:35] >> Oh, so this drink and the the pill that [26:38] we're looking for, that's not easy, [26:40] right? So, we we have some candidate [26:42] molecules. We have a cocktail that [26:43] works, but we want to single [26:45] >> taking this stuff. [26:46] >> Not yet. [26:48] >> You thinking about it? [26:49] >> Yeah. [26:50] >> No one could stop you. [26:51] >> I might. Well, that is true. [laughter] [26:53] >> That is true. But it'd be a bad look if [26:55] I died. So may maybe [26:56] >> I You're not going to die. [26:58] >> I don't think so. We've done a lot of [27:00] safety tests and it looks really safe, [27:02] but I I'm not going to publicly do [27:04] anything against the law. [27:06] >> Of course, [27:06] >> it'll be in private. Of course. [27:08] >> Of course. Not publicly. [27:09] >> No. But we I I'm at a stage where I have [27:11] to be a good boy because I've got the [27:13] world watching. [27:14] >> Yes. [27:15] >> A lot is at stake. [27:16] >> Yes. [27:16] >> And a lot is at stake. [27:17] >> If this trial has any issues, [27:20] >> uh it's not good. We [27:21] >> You got to dot your eyes and cross your [27:22] tees and follow every I understand that. [27:25] But please explain again. I'm being [27:27] rude. I interrupted you. When you're [27:28] telling me that in 2 months it did [27:31] something that would have required 160 [27:33] years of work. Like what do you exactly [27:35] mean by that? [27:35] >> Yeah. And and now we it would probably [27:38] be impossible in in thousands of years [27:41] because what we do is we're looking for [27:43] molecules a single molecule that can [27:45] replace this cocktail. So you need a [27:47] molecule to do three or four activities [27:49] in the cell. Finding one activity is [27:51] what pharmaceutical companies do. It [27:54] takes, you know, hundreds of millions, [27:56] if not billions, to make a drug. We know [27:58] that, right? My little lab of 20 people, [28:02] uh, and students, young kids are trying [28:05] to make one drug do three or four [28:08] different things. That's beyond the [28:10] reach of pharmaceutical experience at [28:13] least 5 years ago. So, what we do is [28:15] we've teamed up with a group at St. [28:16] Jud's hospital where they can take it [28:18] was 10 billion now it's a trillion [28:21] theoretical and also drug known drugs um [28:25] so with my hands I'm showing a big [28:27] funnel and these [28:29] >> you're really good at podcasts you're [28:30] like helping out the audio people and [28:32] everything I love it [28:33] >> I relaunched my podcast that that's why [28:35] >> oh that's why [28:36] >> yeah lifespan David Sinclair um [28:39] shameless plug so that so this funnel is [28:42] uh full of a trillion molecules and we [28:43] have to come down to one how do we do [28:44] that well we Don't look for a trillion [28:47] molecules at the bench. That would take [28:48] 160 or or thousands of years with the [28:51] case of a trillion molecules even with [28:53] robots, even with a lot of graduate [28:55] students. So, we do it inside the [28:58] computer. We just use a lot of compute [29:00] and we dock each of these molecules [29:03] against the enzymes that we now know how [29:05] they work thanks to Google Deep Mind [29:08] solved the problem of how do all our [29:10] proteins look, 20,000 of them. And [29:12] there's a lot of compute. But out the [29:14] other end, a couple of months later, we [29:16] have two I don't have 200 fingers, but [29:19] 200 fing 200 molecules that we can now [29:22] test in the lab within, you know, a few [29:24] weeks. Actually, next week, we're [29:26] testing these 200 against uh human [29:29] cells. And we've also got AI helping us [29:31] to tell us if the human cells go from 92 [29:34] years old back to 20. We can tell that [29:36] just by looking at them thanks to the [29:38] AI. [29:38] >> Is there a way to stop them from turning [29:40] you into a baby? Because that's what I [29:42] would worry about. Yes. [29:44] >> I don't want to be a baby again. [29:46] >> Uh, right. Some people already [29:47] >> I'd like to cut it off at like I was [29:49] pretty good at 25. [29:50] >> You know, that's I'm going to get [29:52] attacked for saying this, but that is [29:53] what we do in the lab. We take 92y old [29:56] cells and they stop at 20ome. [29:58] >> Why Why would you get attacked for that? [30:01] >> Uh cuz on the internet people take a [30:03] clip and they say Sinclair says we can [30:05] all go back to being 20 again. [30:07] >> You suffer from this too, right? They [30:08] take a clip and it's Yes. It's out of [30:10] context. [30:11] >> Yeah. Um, and I'm just saying cells from [30:14] humans, skin cells, we take them back to [30:16] 25. All my students can do this. In [30:18] fact, if you had these little genes, [30:19] OSK, in your garage, you could do this [30:21] experiment. It's not hard at all to [30:23] reverse aging. The question is, how do [30:25] you safely make it a drug? And that's [30:27] been the hard part over the last 10 [30:28] years. Um, so how would it be able to [30:33] regulate [30:34] this reduction or reversal of aging and [30:39] stop it at 20ome years old? [30:42] >> Well, that that's what took so long. It [30:44] wasn't obvious that these three Yamanaka [30:47] genes called OSK were the right [30:49] cocktail. My student who I mentioned, [30:51] Wang, he was struggling. He was trying a [30:55] lot of different genes, most of them [30:56] from embryos, cuz we know embryos have [30:59] to do a reset in the first week of life, [31:01] otherwise they stay the age of the [31:02] parents. [31:05] And he found that leaving out one of the [31:07] Amanaka genes was the trick. And it now [31:10] that we know it's super easy. But in [31:11] those days, he was ready to quit. [31:13] >> How did he find that out? [31:15] >> Well, he tried lots of different [31:16] combinations, hundreds in human cells, [31:18] and you look at the cells to see if they [31:19] get younger. And then we can measure [31:21] molecularly that they get younger. Are [31:23] you measuring them by the length of [31:24] their telomeres? Are you? [31:26] >> Yeah, partly. But actually a better [31:28] measure is uh the chemicals that are [31:31] added and subtracted off DNA itself [31:34] called methyl. And it's just a carbon [31:37] molecule with three hydrogen's. Very [31:39] very simple molecule. But what cells do [31:41] is they use these methals to tag genes [31:44] to be switched off. So when we're [31:46] growing as an embryo, the cells that [31:49] want to become neurons will shut off all [31:51] these other unwanted genes like liver [31:53] genes and skin genes. And the ones that [31:56] don't get this methyl chemical stay on [31:58] for our life. And that's how nerve cells [32:00] develop and stay healthy. But what [32:02] happens during aging? Uh a friend of [32:04] mine, Steve Horvath, discovered that you [32:06] can use this as a clock. These [32:08] chemicals, they change over time. And we [32:10] found that that happens largely due to [32:12] DNA damage going in the sun. These kind [32:15] of things. We could use this to rapidly [32:17] age a mouse. Um, which we published in [32:20] 2023. [32:21] >> Oh, so like maybe like some nefarious [32:23] state actor like some Russian spy could [32:26] like inject something your coffee and [32:28] you would turn 99 overnight. [32:30] >> We know how to do that. [32:31] >> Whoa. That's the dark side of this. [32:34] >> You could you could spike your husband's [32:36] drink. [ __ ] that dude. And turn him into [32:38] an old man. then you suffer. Do [32:42] >> Yeah. So, some someone tweeted the other [32:44] day, "If if a 92year-old could be 25 [32:47] again, would you have sex with them?" [32:50] >> Um, and my response was, [32:51] >> "Yes, imagine how much they know." [32:53] >> But would they have sex with you? [32:54] >> Right? [32:55] >> That's the better question. [32:56] >> That's the question. [32:57] >> They'd be looking for another [32:58] 20-year-old, [32:59] >> right? [33:00] >> Um, so anyway, how do we do it? We we [33:01] can measure those chemicals and [33:03] determine how old a cell is or a human. [33:05] I could take your skin cells from your [33:07] mouth or your blood and tell you how [33:08] old. [33:09] >> People would be so disturbed by like old [33:12] rich guys dating young women if that was [33:15] the case. [33:16] >> You can tell if they looked young would [33:18] >> because people get very mad at that. [33:20] >> You ever noticed? Yeah. Yeah. Yeah. You [33:22] see some real old decrepit dude with a [33:24] hot young wife and people are like, "God [33:25] damn it." They get really mad, [33:28] >> right? Right now the best way to do that [33:30] is to have a big bank account, but [33:31] eventually you'll actually [33:33] >> But people still get grossed out. I [33:34] wonder if they would get grossed out if [33:36] he looked 20. [33:37] >> They'd be like, "He's praying. He has so [33:39] much more years of knowledge and [33:40] information. I don't care if he looks [33:42] 20. [laughter] [33:43] >> That's a 99y old man. [33:46] >> That day will come. That day will come [33:48] where you will not be able to tell how [33:49] old somebody is by looking at them. [33:50] You'll have to do a test for these [33:52] genes." [33:53] >> Wow. I wonder if people still lie about [33:55] their age if that's the case. I wonder [33:57] if it would No one will care. Like you [33:59] would probably lie the other way. [34:01] They're like, "I'm 80." Like [laughter] [34:03] like [34:03] >> That's right. [34:04] >> Tom's over there telling everybody he's [34:05] 80. [34:06] >> That's right. Well, when we live for [34:07] hundreds of years, people will do that. [34:09] They'll be proud of their age. [34:10] >> Do you know anything about um ancient [34:13] civilizations and some of the the [34:16] weirdness of uh the records of like [34:19] ancient Sumere? [34:20] >> Well, only really what I've learned from [34:22] listening to you. Well, it's there's [34:25] what's really weird is the ancient kings [34:28] lists because so okay [clears throat] [34:33] the theory the theory among these [34:36] alternative archaeologist types is that [34:39] there was a very advanced civilization [34:41] that existed on Earth tens of thousands [34:44] of years ago and we were probably wiped [34:46] out by comet impact and what we have [34:49] today is a rebuild of civilization. [34:53] There's not a linear progression from [34:54] caveman to us and that at one point in [34:57] time we had reached great heights. This [34:58] explains the pyramids. This explains [35:01] Machu Picchu uh Sakai Waman. Some [35:04] megalithic structures that don't make [35:06] any sense. These the trilithon stones in [35:08] Balbeck Leadon that are hundreds and [35:12] hundreds of tons that are massive that [35:14] are you know 9 meters off the ground. No [35:16] one understands exactly how they place [35:18] them. [35:20] When you look at the Sumerian kings [35:23] list, it gets very weird because there's [35:26] kings that reign for thousands of years [35:29] and then you have the flood and then [35:32] after the flood, the age of these people [35:35] drops pretty dramatically. [35:37] >> Mhm. [35:37] >> And the rains are after a few hundred [35:40] years become normal. Become like a [35:42] normal person like 50 years, 30 years [35:45] like that. but thousands of years [35:47] before. And then people are looking at [35:49] it like, okay, is this just myth? Is [35:52] this poor recordkeeping? Do they have [35:54] just these, you know, hyperbolic [35:56] elevated stories about these kings? They [35:59] were so amazing. They reign for 30,000 [36:02] years or had they achieved not just in [36:07] building because in building we know [36:09] they had achieved incredibly complex [36:12] structure like the pyramid for instance [36:14] like they had insane engineering somehow [36:16] or another the ability to move these 500 [36:20] ton stones from hundreds of miles away. [36:22] Like how did they do this? We don't [36:24] really know but we know that they did [36:25] it. Did they also [36:29] have the kind of technology that you're [36:31] talking about right now? Because if if [36:33] it's possible today and if that is a I [36:36] mean it makes it very difficult because [36:38] it goes against what you would call like [36:41] the the modern narrative that they're [36:43] teaching in universities in terms of the [36:44] timeline of human history. But if that [36:47] changes and we have undeniable evidence, [36:49] well, it looks like these people were [36:52] far more advanced than we thought and [36:53] there probably was some sort of a reset [36:55] of civilization. What else had they [36:57] accomplished? And had they gotten [36:59] involved in genetic engineering? Had [37:01] they figured out a way to extend [37:03] lifespan? And if they did, imagine all [37:06] the work that you've accomplished in [37:08] your 57 now. About to be 57. [37:12] >> You look great, by the way. Hey, thanks. [37:14] >> You really do. Look at your hair. It's [37:15] so dark. It's incredible. [37:17] >> Uh people speculate it's all fake, but [37:19] it's actually it's not. But anyway, hey, [37:20] >> you're at the [37:21] >> Happy birthday, too. It's coming. [37:22] >> Thank you very much. [37:23] >> Yeah. I don't look as good as you, [37:25] though. Yes, you do. [37:27] >> Physically, you're way better than me. [37:29] >> That's different, though. My face looks [37:31] older. You look You look very young for [37:33] your age. [37:34] >> You know why? [37:34] >> Why? [37:35] >> Cuz I've spent all my time in a lab and [37:37] I haven't gone outdoors for a while. [37:38] >> I'm sure that helps. [37:39] >> That does help. [37:40] >> Um, but my point is, imagine if you had [37:44] 500 years to do research, not just 57 [37:49] years. Imagine if you could continue [37:52] learning and growing. And they did [37:55] develop some sort of a life extension [37:57] technology where you could not just be [38:00] older but be healthier than you've ever [38:01] been before and live for a thousand [38:03] years. You would get so much done. I [38:07] mean the exponential increase in [38:09] technological innovation that we would [38:11] have in this society would be absolutely [38:13] mind-blowing. [38:14] >> Exactly. Exactly. Exactly. This is a [38:17] >> what these alternative history people [38:19] think that might be what had taken place [38:21] tens of thousands of years ago. [38:23] >> Yeah. Well, I'm a Harvard scientist, so [38:25] I'm not going to say anything that [38:26] isn't. [38:26] >> Of course, that's for me. [38:29] >> Yes, [38:29] >> that's where I live. [38:30] >> That's why I shut up. But but you you [38:32] did make some really important points. [38:33] One is that ancient civilizations were [38:36] have always been way more advanced than [38:37] we think [38:38] >> and dinosaurs a lot more real than we [38:41] make them look. These this we always get [38:42] things wrong looking back in time [38:44] >> and looking forward in time. Uh but the [38:46] other thing that you said which is [38:47] really important is that if if we do [38:49] have extension of human lifespan like [38:50] the Bible and and these civilizations [38:52] suggest [38:54] then how will you think about your life [38:57] if being a 100 is you know you're still [38:59] in your prime you you do things very [39:02] differently who would you marry what [39:04] career would you think about you might [39:06] have multiple lifetimes multiple [39:08] marriages multiple families and that [39:11] will happen it's not really a question [39:13] of if anymore it's like asking the right [39:16] brothers. Will we fly? Yeah, we we built [39:17] the glider. Are we going to fly around? [39:19] Question is, will we build a Concord? [39:21] Will we go to space? And I think that [39:23] will happen. [39:24] >> Yeah. No, I think so, too. I I I I think [39:27] Well, certainly one thing that we know [39:29] is that there's a giant difference [39:30] between people who are 57 years old [39:32] today versus 57 years old in the 1930s. [39:37] It's just a giant difference. A giant [39:38] difference in your physical ability, [39:40] your health. [39:41] >> We'd be old men. [39:42] >> Yeah, we would be old men. And what um I [39:45] mean when I was a child I thought of [39:47] people I'm almost 59. I'll be 59 in a [39:49] week. I used to think of a 59year-old as [39:53] being basically dead. Like you you're [39:56] you're barely getting around. You know, [39:58] you're probably tired all the time. [39:59] >> Looking to retire soon. [40:00] >> Yeah. Looking to retire. You got no [40:02] energy. I'm filled with energy. I'm [40:05] constantly doing How old is he? 60. [40:08] >> That's what it says. I mean, [40:09] >> oh no. [40:09] >> I don't know if that's accurate. [40:10] >> That's I I bet that's accurate. They had [40:13] no [ __ ] vitamins. Nobody knew what [40:16] like what the proper nutrients you [40:17] should take were. Nobody knew the what [40:20] was really important in terms of like [40:22] resistance training and sleep and red [40:24] light therapy and all that jazz. [40:25] >> And they were doing all the bad stuff [40:26] like heavy smoking, drinking, not [40:29] sleeping a lot. [40:30] >> Yep. Not sleeping a lot. Heavy and who? [40:32] Pesticides and all kinds of terrible [40:34] [ __ ] [40:35] >> 60-year-old. What? That guy's 60. [40:38] >> Crazy. [40:38] >> No way. [40:39] >> I don't know, man. [40:40] >> Come on. Shut up. That guy's [ __ ] 28 [40:43] [laughter] years old. There's no way. [40:44] That guy's 60. Is that real? [40:47] >> I doubt it. I doubt it. How about that [40:48] guy that looks 50 and he says, "Everyone [40:50] thinks I'm 18." Like, yeah, sure. [40:53] >> What's that? There's a guy uh on [40:55] Instagram, which I occasionally visit. [40:57] And he obviously looks old. Like he's [41:00] looks [41:01] >> Oh, he's a crazy person. [41:02] >> And he says, "People think I look 18." [41:04] Like, are you crazy? [41:06] >> Well, there's a lot of crazy people out [41:07] there. There's a lot. Well, that's body [41:09] dysmorphia. You know, [41:10] >> there must be [41:11] >> bodybuilders. They think they're tiny. A [41:12] lot of people people are crazy. [41:14] >> Yeah. [41:14] >> A lot of people have a distorted [41:15] perception of what they look like. [41:17] >> Yeah. The the plastic surgery industry [41:19] is massive. It's just growing and [41:21] growing. You can see [41:22] >> it on the street. Uh LA especially. But [41:25] imagine a world where [41:27] >> if I'm successful, you can take a pill, [41:29] your doctor could get it or eventually [41:31] it's a cream on your face and you [41:34] literally get younger. We do this in [41:35] mice already. The mice get younger. Is [41:38] it going to work in humans? I think it's [41:39] just a matter of time. [41:40] >> So, in the mice uh experiments, what [41:44] have you achieved? [41:45] >> Well, a lot you know, I can reveal here [41:48] uh [41:50] some of it uh for the first time. We [41:53] this this pill that we give them, it's a [41:54] drink actually cuz they can't chew the [41:57] mice within 4 weeks with this cocktail. [41:59] It has three components which are top [42:01] secret. My lab is sworn to secrecy. They [42:04] after four weeks, we give it to them [42:06] three days a week. um Monday, Wednesday, [42:08] Friday, weekends off. Within those four [42:11] weeks, they get better physically, [42:13] mentally, [42:14] excuse me. They uh so we put them [42:16] through tests if just in a couple days. [42:19] >> Oh, no. Three days a week for a month. [42:21] >> Oh, okay. [42:21] >> I found this guy's Instagram. [42:22] >> This is the guy. [42:23] >> He went viral last year. He's being 59 [42:26] years old. [42:27] >> What? [ __ ] It seems so not real. [42:30] >> He looks crazy. [42:32] >> Maybe 30. Exactly. [42:33] >> He might have just amazing genetics. [42:36] Well, look at Yoel Romero. There there [42:39] are people that are freaks [42:40] >> from Singapore. [42:41] >> Yeah. [42:41] >> Wow. [42:43] >> Quando Tan something. [42:44] >> And he's 60 years old. [42:46] >> Yeah. He's been gone I mean followers. [42:49] Yeah. I don't know. [42:50] >> He certainly doesn't look like he's had [42:51] a facelift. His skin is [ __ ] [42:53] incredible. [42:54] >> Yeah. But he's probably never been in [42:55] the Sonic full a full AI account that's [42:59] trolling everyone. I don't know. [43:01] Probably [43:01] >> that's possible, too. Like look at that [43:03] picture right there. Like that looks a [43:04] little AIish. Go back to that one again. [43:07] Keep your pants on, Jamie. [laughter] [43:09] >> Relax. Relax. [43:10] >> That looks very AI, doesn't it? [43:12] >> It I'm just It could be is all [43:15] >> his 59th birthday. His whole thing is [43:18] that he's young for his [43:19] >> 58 looks half his age. [43:21] >> Wow. I mean, [43:23] >> this will be normal. [43:24] >> Yeah. This is 2024, so it's not This has [43:26] been going on for a while. [43:27] >> Okay. So, this is pre AI. [43:29] >> Yeah. If it's fake, then he would have [43:30] been called out now, I feel. [43:32] >> Right. So, he might just be a genetic [43:34] freak. [clears throat] [43:34] >> Could be. Yep. [43:36] >> Which is interesting, right? Like do you [43:37] guys study the different like you know [43:40] unfortunately certain people that have [43:42] like like pale people for instance with [43:44] thin skin [43:45] >> they they age hardcore they go [43:47] >> and there are those kids that get old in [43:49] their teens. We study that as well. [43:51] >> Yeah. [43:51] >> We're reversing that too. [43:53] >> Uh but yeah we we do study the genetics [43:55] of aging. [43:56] >> That's the real application for it where [43:59] people are going to be excited about it. [44:01] People that have that what is it called? [44:02] Pgeria. [44:03] >> Pgeria. Exactly. [44:04] >> Yeah. [44:04] >> Yeah. And so we have mice that have this [44:06] same gene mutation and they get old [44:08] really quickly and we're giving them the [44:09] drink right now. [44:11] >> And so in the drink you give it to them [44:13] how often and for a month. [44:15] >> It's once a day, every other day, 3 days [44:19] a week for a month. And uh yeah, in [44:23] normal old mice, we see them fitter, [44:25] stronger, better memory. They run around [44:27] the cage [44:28] >> in just a month. [44:29] >> It's amazing. We only did a month [44:30] because it was Christmas uh holiday [44:32] season. He didn't we didn't want to go [44:34] for longer but uh it worked in 4 weeks. [44:37] I'm shocked even these genes require 6 [44:39] to 8 weeks to work for revision uh [44:42] recovery of vision. [44:44] >> And so this this is working on a [44:46] different pathway. [44:47] >> Well, here's the cool thing. We we think [44:50] it's working through the same mechanism, [44:51] the reboot, the reinstallation of [44:53] software, um the drink because there are [44:56] genes called TETS. There are three of [44:59] them in the body and they do something. [45:01] spell that [45:02] >> te capital t. There's one, two, three. [45:05] >> And these are genes that make enzymes [45:08] that remove these methals off the DNA. [45:10] >> So they they control the clock. And if [45:13] we get rid of those genes, our system [45:17] doesn't work. We cannot restore vision [45:19] and our pill doesn't work without [45:23] removing and altering those chemicals. [45:24] So in other words, it's not just because [45:26] the chemicals make the cell healthier. [45:28] It's actually resetting this clock on [45:31] the DNA. Whoa. [45:33] >> And that was the big deal. I said wo [45:35] when my student told me, and that's why [45:37] I think it got the cover of Nature [45:39] magazine, which is we're actually [45:41] looking at the the clock of life. And [45:43] we've realized that this clock that goes [45:46] around, this biological clock isn't just [45:49] a clock. When you move the hands of the [45:51] clock, time goes backwards for the body. [45:55] Meaning the clock is aging. And aging is [45:58] the clock. [46:00] >> Wow. What is it? I It's You don't really [46:03] know in terms of humans, but is there [46:06] any indication that improves cognitive [46:09] function in mice? [46:10] >> Yes. Um I can say without a doubt that [46:12] other labs and ours have shown that when [46:15] you reverse the age of the brain in a [46:16] mouse, it gets better at learning. And [46:19] we even have some hints uh and we're [46:22] going to publish this that lost memories [46:24] come back. [46:25] >> Whoa. So Alzheimer's patients, I [46:28] believe, still have memories. They just [46:30] cannot access them. And that one day we [46:32] can reverse Alzheimer's disease by [46:34] making the brain young. And that using [46:37] that approach, making the whole body [46:39] young, we can cure diseases that are [46:41] currently incurable. [46:43] >> Holy [ __ ] [46:46] Well, young people don't get [46:47] Alzheimer's. Why? Because the body can [46:48] tackle the problem. The young body can [46:51] heal itself. So my approach is make the [46:53] body young, it'll heal itself in every [46:55] way. [46:57] >> Well, do you have children? [46:58] >> Three. [46:59] >> Yeah. One of the things that's just [47:01] phenomenal is watching them heal. [47:04] >> Yeah. [47:04] >> I'm like it it is so uh it's so wild, [47:08] but also you envy them so much cuz they [47:10] get a cut and it's like two days later [47:13] like where's your cut? It's [ __ ] [47:15] gone. Like that's crazy. Like my [47:17] daughter had a um a cutter. She fell and [47:19] knocked her head and she had this like [47:21] dark spot on her head like where where [47:23] she got injured and like four or five [47:25] days it was gone and I was like that [47:27] [ __ ] thing would be with me for 4 [47:29] months. [47:29] >> Yeah. And the good thing is if we rub [47:31] our cocktail on the skin of the mice [47:33] they heal like they're young again. [47:35] >> Oh so that would be like a great [47:37] application for ladies who want the [47:38] beauty treatment on the face, right? [47:40] Because it would just [47:41] >> where we're headed. [47:42] >> Whoa. It would just [47:43] >> Yeah. And we're working on hair. We can [47:45] grow human hair on mice now. [47:47] >> Really? That took a few years and now we [47:49] can check if we can regrow hair and make [47:51] it dark again. [47:52] >> You can grow human hair on mice. [47:54] >> Yeah, I'm not allowed to. Actually, I [47:55] did post it on Instagram and the [47:57] university said, "Get that down." Um, [47:59] but it exists. We grow it from stem [48:02] cells from human stem cells. We make [48:04] little balls of hair. Takes a few [48:06] months. We open up the ball to make a [48:08] flat piece of skin, human skin, and we [48:11] put that in the back of a mouse that can [48:14] accept human skin. And then you get [48:16] black toughs of hair from humans in a [48:17] mouse. [48:18] >> Can you get any kind of hair? Like could [48:19] I get an afro? I just want to get one to [48:20] piss people off. [48:22] >> I'd love an afro. Like a Colin [48:24] Kaepernick type. Just a big crazy one. [48:26] >> Yeah, we could grow grow hair. [48:28] >> We can do that. We We're one of the few [48:30] labs that can grow this hair. [snorts] [48:31] >> So I thought about doing that for a [48:33] company, but I think hair transplants [48:34] would just be easier. [48:36] >> Oh, right. So you would grow hair in a [48:38] lab and then transplant those hairs. [48:39] >> We can do that. Yeah. Oh, well that's [48:41] the thing because I got a hair [48:42] transplant. But the way I describe it is [48:44] like you're take it's like taking people [48:48] that are really healthy and moving them [48:50] into a town where everyone's dying cuz [48:52] like you're take you're taking hair from [48:55] back here where it's going to stay and [48:56] you're putting it up here where it's all [48:58] falling out. [48:59] >> Oh, it didn't thrive. [49:00] >> What's that? [49:00] >> It doesn't thrive if you move it. [49:02] >> Oh, it thrives but everybody else dies. [49:04] >> Oh [ __ ] [49:05] >> But you know, you can only take so much [49:06] from the back of your head and move it [49:08] to the top of your head. That's why a [49:10] lot of guys with hair transplants look [49:12] goofy cuz you have like this strong [49:14] hairline in the front and it goes back [49:16] like that and then everything else looks [49:17] like chaos. [49:18] >> Oh, that sucks. You know what I take for [49:20] my hair? [49:20] >> What do you take [49:21] >> among other things? [49:22] >> Uh, Viagra. [49:25] >> Viagra. [49:26] >> Yeah, actually it's I shouldn't say the [49:28] brand name. [49:28] >> That's why I take it for my hair. [49:30] >> That's what I tell everybody. That is [49:32] true. It's low dose. 7 milligrams a day [49:34] of tadelopil [49:36] >> and it's good for a lot of things. A lot [49:38] of things. I know it's good for [49:39] endurance. [49:40] >> Yeah. [49:41] >> Yeah. I cuz I know athletes who take it [49:43] for endurance, they probably take it to [49:45] [ __ ] too. Let's not kid ourselves. [49:48] >> Well, it's a nice it's a nice benefit. [49:50] Um when a scient a paper just came out [49:53] about its role in preventing cancer. Uh [49:56] I tweeted what what's not to love. It [49:58] people love that tweet. But the point is [50:01] actually last week they found that these [50:03] drugs in mice and seemingly in people [50:07] who take these drugs are actually [50:09] resistant to can certain types of [50:11] cancers like head and neck cancer. [50:13] >> So they're turning out to be really [50:14] important [50:15] >> blood flow. [50:16] >> Well two reasons um that are not related [50:18] to blood flow but they're related to [50:20] what's called nitric oxide signaling [50:22] which is what helps dilate blood vessels [50:24] in all your body including your penis. [50:26] The other two mechanisms, one showed [50:28] that toalophil is good for uh exposing [50:32] the tumor to the immune system. There [50:34] are uh certain cells uh called um MDSC's [50:38] that protect the tumor from getting [50:40] attacked and the drug stops that. So now [50:43] the tumors shrink in mice and seemingly [50:46] in people in tumors. And then the second [50:48] mechanism is really interesting. It [50:50] seems to this was sedanaphil. This is [50:53] now Viagra found that the cancer is uh [50:57] th a lot of cancers thrive on [50:59] cholesterol and this blocks the ability [51:01] of cancer cells to use cholesterol. [51:03] >> I thought they thrived on glucose [51:04] >> that too. Exactly. Right. So you want to [51:07] be in ketosis if you've got a tumor in [51:10] general. So fasting is good. But now it [51:13] looks like [51:15] >> these ED drugs are might be good for it [51:17] as well. [51:18] >> Fascinating. And wasn't um I think [51:23] Viagra was a s it was an accident, [51:26] right? Wasn't wasn't it a blood pressure [51:28] medication? [51:28] >> It's a good story. It was for angina, [51:29] right? It was for your for your heart. [51:31] Um but the story goes that women [51:34] especially and and the men didn't want [51:36] to give up the drugs that they had left [51:38] over. [laughter] [51:40] It it was amazing. It was I think it was [51:42] 75% had a positive reaction for [51:44] erections and without it 22. So, it's [51:47] it's very clear that it was working. [51:50] >> Interesting. And so, uh so how does it [51:53] help hair? [51:54] >> Uh well, we don't know for sure, but [51:56] there's a lot of evidence that part of [51:59] the reason hair dies out and stops [52:01] growing is a lack of blood flow. And the [52:03] minoxidil that people put on their hair [52:05] helps with that. [52:06] >> Right. Interesting. And then DHT [52:09] inhibitors. [52:10] >> Exactly. [52:11] >> Also help. [52:12] >> That'd be dueide. Uh people can take [52:14] orally. [52:15] >> Yeah. The problem with that is uh my [52:17] friend had severe depression when he [52:19] took that. [52:20] >> Yeah. [52:20] >> It really [ __ ] him up and he didn't [52:22] realize cuz it he didn't understand that [52:25] that was the he was like what is wrong [52:26] with me? And he was getting suicidal and [52:29] then he got off of it and it just went [52:30] away and he's like oh my god I can't [52:32] believe that. This episode is sponsored [52:34] by BetterHelp. You've probably heard [52:37] about BetterHelp before but maybe you [52:39] haven't heard from those who have [52:41] actually used BetterHelp. That feedback [52:44] can tell you everything you need to [52:46] know. Go to betterhelp.com/reviews [52:49] and check out the feedback from hundreds [52:51] of people saying how much they love this [52:54] service. It's easy to see why. To get [52:57] started, all you have to do is answer a [52:59] few questions. You'll get matched up [53:00] with a therapist based on your needs. [53:03] And if it's not the right fit, you can [53:05] switch therapists at any time. See the [53:08] reviews, see what stands out, and see if [53:10] BetterHelp is right for you. Visit [53:12] betterhelp.com/j. [53:15] That's betterh elp.com/jre. [53:20] >> Yeah. Well, I I I'm taking it for a [53:24] number of reasons, including my hair and [53:26] my prostate. See if I can keep it from [53:28] growing. But, uh, fortunately, I haven't [53:31] had that side effect. But, everything [53:32] >> it depends, right? It varies [53:34] biologically depending on the person. [53:35] >> Yeah. It's important when either of us [53:37] says that drug's good, that drug's bad, [53:40] people realize that you have to test it, [53:42] see, and with doctor's supervision. [53:44] >> Yeah, that was where where I was going [53:45] to get to was like because different [53:48] medications have different reactions or [53:50] different people's reactions to [53:51] medications, they they vary quite [53:53] wildly. So, like before you [53:56] make this public, like how how do you [53:59] determine whether or not this is going [54:01] to be safe for a wide variety of people [54:05] to reverse aging? [54:06] >> Oh, my drug um our drug that we're [54:08] making. Well, we will test it on a lot [54:11] of people before it goes out into the [54:14] the wide world. [54:15] >> And you've started testing it on people [54:16] so far? [54:17] >> Yeah, there are people right now who [54:18] have this these genes in their eye. And [54:22] how's it going? [54:23] >> Uh, I'm not allowed to say, but [54:25] >> can you wink twice if it's great? [54:27] >> Um, I would say that everything's uh on [54:31] target. [54:32] >> Okay. [54:32] >> Um, [54:33] >> that's good to hear. [54:34] >> Nothing bad to report. [54:35] >> Nothing bad to report. [54:36] >> Yeah, I think those might be the words [54:37] I'm allowed to say. [54:38] >> And is that the only clinical trials [54:40] you've used with any of these [54:41] applications for for humans? [54:43] >> So far, that was the first glaucoma and [54:45] also sudden blindness. Um, it's called [54:48] Nion, which is now twice as more [54:50] prevalent because of the GLP1 drugs. [54:53] >> Really, [54:54] >> it's not well known. Obviously, [54:56] companies don't want to talk about it, [54:58] but yes, sudden blindness has doubled [55:01] seemingly because of these meds. So, you [55:03] have to [55:04] >> Holy [ __ ] Sudden blindness has doubled [55:07] because of GLP1s [55:09] >> due to Nion, which is like a stroke in [55:11] your eye. And then your other eye can [55:13] go, which is pretty scary. and there's [55:15] nothing you can do about it. Hopefully, [55:17] our drug does work for those people. [55:20] >> And well, obviously correlation does not [55:24] equal causation, but it seems to be [55:27] >> Yeah, there's a a scientist at Harvard, [55:29] you could look up his work, um Joe [55:31] Rizzo. It looks like it's repeatable [55:34] across the planet. [55:35] >> Wow, that's terrible because there's so [55:38] many people out there that are just [55:39] telling everyone they should get on [55:40] GLP1s. Yeah, [55:42] >> I've seen that like by online people [55:45] like online podcasters saying everyone [55:47] should get on GLP1. This is a [55:49] groundbreaking technology. This is [55:51] amazing. It's going to transform [55:52] society. I'm like, [55:54] we just started taking these. The [ __ ] [55:57] are you saying? [55:58] >> Yeah, it's not risk- free. Same with ED [56:00] drugs. [56:00] >> Here goes. Recent study suggests that a [56:02] potential rare link between GLP-1 [56:05] receptor agonist medication such as [56:07] ompic waggoi blah blah blah and a [56:10] condition called nonarteritic [56:13] anterior [56:15] what's that word iskeemic [56:17] >> iskeemic optic neuropathy [56:20] >> an eye stroke can cause sudden painless [56:23] loss of vision in one eye while absolute [56:25] risk remains very low anyone experienced [56:28] sudden vision changes should seek [56:29] emergency metal medical eval valuation [56:31] immediately. Well, very low is like [56:34] >> it's still in 10,000 people. [56:36] >> One in 10,000. [56:37] >> Yeah. [56:38] >> Yeah. That's [56:38] >> Oh, no. Total of 10,000. [56:40] >> Oh, total of 10,000 so far for how many [56:42] people are taking this stuff? [56:43] >> I think it's pretty [56:45] >> The drugs were 68.6 [56:48] times more likely to develop this and [56:51] eight times more likely to develop [56:53] diabetic. What is that? [56:57] >> We only got the blurb. [57:01] Oh my god. Then wow. [57:07] >> Yeah, man. These [clears throat] things [57:08] are just they're just rolling out and [57:11] the people that are like super [57:12] enthusiastic and also they have some [57:15] sort of a financial interest in [57:17] promoting these things which often times [57:19] does seem to be the case with a lot of [57:20] these people. They have either stock in [57:22] these companies or some sort of a stake [57:24] in them. [57:26] >> Uh yeah, it's true. Though I will I will [57:28] say to counter that that the GLP-1 drugs [57:30] have probably saved millions of lives [57:31] already and they're pretty common. I [57:33] think it's 10% of people are trying them [57:35] and 25% want to. [57:36] >> Yeah. I mean they don't work for [57:38] everybody. I have a good friend of mine [57:39] that had a terrible reaction from it and [57:41] he was hospitalized and [57:42] >> Oh no. But I know other people where [57:45] it's completely transformed their life [57:46] and they've lost a ton of weight and [57:48] particularly people that just for [57:50] whatever reason the food addiction was [57:52] so incredibly strong that whatever their [57:56] constitution the way they're the way [57:57] they're designed the way they're built [57:59] the way they've evolved as a human being [58:01] they weren't capable of overcoming it. [58:03] They take the GLP1s and then they sort [58:06] of start getting moving and then they [58:09] lose all the weight. They start feeling [58:10] better. they start making a lot of other [58:12] positive changes. You get that momentum [58:14] which I I always talk about is which is [58:16] one of the most important things for [58:17] transforming your life. Everyone wants [58:19] to talk about discipline. I think [58:21] discipline is the primary that's the [58:23] main engine. But one of the things that [58:25] comes along with any kind of an exercise [58:28] program or changing your life program [58:30] where you you start getting positive [58:31] results is momentum. And momentum is [58:33] absolutely huge. Thank you. [58:35] >> Because then you start feeling soant [58:37] this is good. So, I think GLP1s are [58:39] fantastic for getting people going. [58:41] >> Yes. Everybody should hear this. It's [58:43] really important. I'll give you my [58:45] example. It's a classic case. I couldn't [58:49] fast for more than about a day. I wanted [58:52] to do more. I know that 3 days fasting [58:54] is good. A week can be even better, but [58:55] I couldn't do it. I was I don't have a [58:57] lot of willpower when it comes to this [58:59] kind of stuff. [59:00] I tried a Jelp1 receptor agonist. I gave [59:03] it and it was easy. I didn't even feel [59:05] like I needed to snack at night, which [59:07] is one of the things that I and many [59:08] people suffer from. But the fact that I [59:10] could do it, I went off the drug. I [59:13] didn't need it. But now I can fast for I [59:16] went for two weeks uh in a couple of [59:19] months ago. [59:19] >> It's easy now. I now that I know that I [59:21] can do it mentally, it's not hard at [59:24] all. [59:24] >> The momentum. [59:25] >> Exactly. I know what's possible. [59:27] >> Yeah. Yeah. That's fascinating. Um, you [59:32] are you still on a plant-based diet? [59:34] >> Mostly. [59:35] >> Yeah. I what I had I just had a a [59:38] conversation with a friend of mine about [59:40] this. I don't know how much of the [59:41] information that he was telling me was [59:42] totally accurate, but what he was saying [59:44] was that um he was told before he did [59:48] fasting that one of the be a runner, he [59:52] said one of the best ways to get into [59:54] fasting is to get your body into ketosis [59:58] first. He said, and what he thinks is [60:01] that a carnivore-based diet and what he [60:04] was told was a good way if you could do [60:06] that for a few weeks, it mitigates your [60:08] appetite. Like one of the things that [60:10] happens with a lot of these diets that [60:12] uh regulate insulin resistance is that [60:16] when you get used to consuming just fats [60:19] and protein, you don't have the kind of [60:21] hunger pangs that you have with [60:23] carbohydrates. Like when I if I go in a [60:27] bad streak and I'm eating pizza and [60:29] pasta and and I've done that in the [60:32] past. I don't really do that much and [60:33] all unless I'm on vacation. [60:35] >> In the in the past though, when I would [60:37] get hungry, I would get crazy hungry. [60:40] Like I I've got to eat now. I don't get [60:42] that at all anymore because I'm mostly [60:44] on a carnivore-based diet. Mostly what I [60:47] eat the like you look at the bulk of my [60:49] diet, it's meat and fermented [60:51] vegetables. It's meat and like kimchi [60:55] and sauerkraut and stuff along those [60:56] lines. And when I eat like that, my [60:58] hunger is very easy to control. And I've [61:02] gone 24 hours like like it's nothing, [61:05] not eating. It's like not a problem at [61:06] all. But that's the most I've ever [61:08] fasted is 24 hours. [61:09] >> Okay. Well, see if you can go for three. [61:11] Um it's really worth it. You feel really [61:14] great. Um ketosis is one. [61:15] >> That's what everybody says. [61:16] >> Yeah. Yeah. And you go into what's [61:18] called deep cleansing. It's called um [61:20] chaperone mediated autophagy or CMA and [61:23] a friend of mine in New York uh Maria [61:25] Corvo studies this and it cleans out a [61:28] lot of the old proteins in your body. So [61:30] ketosis doesn't just make you feel good, [61:32] you're actually renewing your protein in [61:34] your body and rebuilding it. And so I I [61:37] do that as a as an anti-aging thing. [61:39] >> What I find is the biggest benefit is uh [61:41] mental acuity. It it's a gi it has a [61:44] giant impact when I stick to the diet in [61:47] terms of my ability to form sentences [61:50] like recall information and just be [61:53] present in in podcasts. [61:55] >> Yeah. So in in in my podcast it's what [61:58] you do is really quite difficult. It it [62:00] you make it look easy. So when I'm when [62:02] I'm doing my podcast and often it's solo [62:05] so it's challenging. Um I forget things. [62:08] I have to remember hundreds of papers [62:09] for these things. They're quite hard. Um [62:11] either I'm going to fast and if I don't [62:12] remember to fast. Um I did an [62:14] experiment. I took some ketones. You can [62:17] drink these things, you know, right? So [62:18] >> there's the one uh the little drink I [62:20] think was ketone IQ. Ketone IQ. [62:22] >> Yeah. Fantastic stuff. [62:23] >> Yeah. Yeah. I use that. [62:24] >> I love that stuff. I do that. I take [62:25] that before I do UFC broadcasts a lot of [62:28] times. Yeah. [62:29] >> Um I actually took some before [62:31] >> because one that's great before podcasts [62:32] as well. One one of one more difficult [62:34] things that I do is the UFC commentary [62:36] because it's six hours [62:38] >> Uhhuh. Six hours of talking on air live. [62:42] Wow. [62:42] >> Yeah. And about fights and and I'm also [62:44] recalling fights and I'm also I'm seeing [62:46] positions. So I have to remember in my [62:49] mind how this is finished because like [62:51] in jiu-jitsu there might be I don't know [62:53] how many positions there are. There's [62:54] thousands and there's moves where I'm [62:56] like what is he doing? What is he doing? [62:58] Oh. Oh. Oh that's that that's the [62:59] provian necktie. I'm I'm looking at his [63:01] arms a bit. Like your brain is f I am [63:04] exhausted at the end of 6 hours and [63:06] [ __ ] starving. Like after the UFC is [63:09] over, I can eat so much food. It's I'm [63:12] so hungry. [63:12] >> But you take a little drink. [63:14] >> I take a little ketone. Little ketone [63:15] IQ. I take uh neutropics. I drink this [63:18] stuff. My friend Derek makes this is [63:20] Gorilla Mind. This is a um a neutropic. [63:23] >> Oh, I got [63:23] >> So it's a neutropic cocktail with uh um [63:27] uh caffeine in it. This stuff's really [63:28] good for a podcast. I also take Alpha [63:30] Brain. Alpha Brain Black Label is [63:32] phenomenal for that. There's a bunch of [63:34] different ones that I take. Uh the gum [63:37] neurogum. Neurogum is excellent for [63:39] that, too. But I just do [ __ ] [63:41] everything I can to maximize. [63:42] >> That's how you do it. All right. Secret [63:44] is now out. All right. It But what you [63:45] do is amazing. And I thought you were on [63:47] medapanyl or something. [63:48] >> No, I've I've taken that before in the [63:50] past. But uh the problem with that stuff [63:53] is I think I like it too much and I want [63:56] to take it all the time. I you know when [63:57] I used to take that if I had a gig in [63:59] San Diego and I drive home uh after the [64:02] gig and it was like you know one o'clock [64:04] in the morning when I'm done and then [64:06] I'm like I'll just go home and it's only [64:08] two and a half hours and I start making [64:10] the drive and you just get so tired. But [64:12] if I take New Vigil or Provigil before I [64:16] do that I would be able to drive no [64:18] problem. Put a book on tape on [64:20] >> what's that? [64:20] >> Can you sleep after that? [64:21] >> Oh yeah. It doesn't seem to affect your [64:24] ability to sleep which is really [64:25] interesting. It's not like caffeine. Do [64:27] you do it? Do you take it at all? [64:29] >> Uh armadapanil for talks when I'm you [64:31] know traveling. [64:32] >> Does it help you? [64:34] >> Definitely. [64:34] >> Would it like in what way? [64:36] >> Um it it gets rid of my jet lag and I [64:39] can focus. [64:40] >> My brain often uh is either scattered or [64:43] filled with facts that I causes me like [64:45] now to not be able to talk properly. But [64:47] if I'm on it, which I'm not, [64:49] >> I'm I'm on point every time. [64:52] >> For me, the best thing for jet lag is [64:54] exercise. There's something about rigor [64:56] rigorous exercise. It doesn't even have [64:59] to be long. It just has to be where my [65:02] heart rate gets really elevated like [65:04] above 150 beats per minute for 15 20 [65:07] minutes. Like I have to really go hard [65:09] where I'm sweaty and breathing heavy you [65:13] know especially if I could jack it up to [65:14] like 180 190 like I'm doing like Tabata [65:17] sprints on an aine bike. That kind of [65:19] stuff completely resets me. [65:21] >> Yeah. hard kettle bell workouts. Like [65:23] I'll do like a hard series where minimal [65:26] amount of rest in between. So I'm really [65:28] pushing it. Once I relax, I'm back. It's [65:31] like it to it whatever it is where your [65:33] body just needs to like shake it up and [65:36] like get all of it out of your system. [65:37] It's like now I feel completely normal. [65:39] >> Yeah. Well, you might remember last time [65:42] we talked about hormesis. Yes. What [65:43] doesn't kill you makes you stronger. And [65:45] that's what you're doing. You're putting [65:46] your body into survival mode. So, one of [65:48] the reasons I eat mostly plants, why I [65:51] take enma and these other molecules is [65:54] to mimic that. I don't work out like you [65:57] do. Um, I should, but I don't. And, uh, [66:00] >> why don't you? [66:01] >> Uh, I think partly because I tell myself [66:04] I'm too busy, [laughter] [66:06] which is [ __ ] Uh, I need a I need a [66:10] partner uh who will motivate me. I think [66:12] that would help. [66:13] >> Maybe just get a trainer. [66:15] >> That's that's a solution. [66:16] >> You got some cheddar. Get a trainer. [66:19] >> I got some share. I was that money. [66:20] >> Money. Yeah. No, I can definitely afford [66:22] [laughter] one. Uh, yeah. No, you know, [66:24] it's on me. I actually I I will own that [66:27] that I have to get I just was explaining [66:29] this to my friend last night who's like, [66:30] I got to start working. I'm like, just [66:31] get a trainer. Get a trainer, someone [66:33] who's good, and that way they'll develop [66:36] a program for you. All you have to do is [66:37] just show up and do what they tell you [66:39] to do. Just do it. And it's mindless. [66:42] You could just like just go through what [66:44] they tell you to do and you'll just you [66:46] trust the process. You'll improve [66:48] radically. [66:49] >> All right. All right. Here's what we're [66:50] going to do. [66:51] >> Okay. [66:52] >> I'm going to take you. [66:54] >> Here's what we're going to do. You're [66:55] going to get me a jug of that [ __ ] [66:56] juice. [66:57] >> This stuff we'll [laughter] swap. All [66:58] right. And you'll be my trainer. [67:00] >> I'll be your trainer. [67:01] >> Well, [67:02] >> I will. I I've done that before with my [67:04] comedian friends. [67:05] >> Really? [67:05] >> Sure. [67:06] >> Yeah. I'll just come [67:07] >> I do it the right way where I take them [67:09] through it very easy. I don't have them [67:12] work out hard at all, especially in the [67:14] beginning. Everything is like nice and [67:16] easy. It's like a little bit of strain. [67:18] You're not going to be exhausted [67:19] afterwards. And we build you up. I'm I'm [67:22] a bu I'm a I I'm a firm believer in not [67:25] overt taxing the system on people that [67:27] are sedentary. [67:28] >> I really think it's a slow gradual [67:30] process. I I think you have to get [67:32] better the same way you got sick over [67:34] time. [67:35] >> Okay, good. [67:36] >> You can make radical changes in a short [67:38] period of time, don't get me wrong. And [67:40] even just a little bit of, you know, [67:43] moderately rigorous exercise, a few days [67:46] a week will a few days a week will give [67:48] you great improvements. But I'm not one [67:50] of those guys is like, you know, we're [67:52] going to do two hours today and you're [67:54] going to go to failure and you're going [67:55] to be throwing up in a garbage pan. [67:56] You're not going to do that again the [67:58] next day. I want you to do it again the [68:00] next day. I want you to have a a nice [68:02] workout where, you know, you're doing [68:04] like 10 push-ups and 10 sit-ups and 10 [68:06] bodyweight squats. And then we're going [68:07] to do some of these kettle bell cleans [68:10] and kettle bell. Nothing hard. Like [68:12] everything's going to be like, okay, you [68:15] put it down, you're fine. And I want you [68:16] to leave rejuvenated, like you feel [68:19] like, oh, that was like exhilarating. [68:21] Nothing crazy. And then we'll slowly [68:23] start to add a little bit over time. [68:25] That's what I think the right thing to [68:27] do with people who don't work out all [68:28] the time. You can't just jump in and, [68:32] you know, [68:32] >> it's like fasting and skipping meals. [68:34] You just can't do a day or three without [68:36] practicing. [68:37] >> Well, it's also you're going to get [68:38] injured. And this is one of the main [68:40] things that happens to people that dive [68:41] right into the deep end of the pool when [68:42] they start working out is they get hurt. [68:44] They get muscle poles. They get [68:45] backachches. They get all these [68:47] different things that happen because I [68:48] think you just pushed your body too [68:50] quickly. You know, it's like you're [68:52] you're in boot camp. Like, well, you [68:54] don't have to be in boot camp. This is [68:55] not the way to do it. The way to do it [68:57] is like slowly build up and trust the [69:00] process slowly. Start by if you're [69:03] overweight like my friend Jelly Roll. He [69:05] lost 250 lbs. What did he do? Started [69:07] walking. Just started walking. Walking [69:09] around the neighborhood, walk around the [69:11] block, walk upstairs just slowly and [69:14] then change the diet and then add some [69:16] stuff and next thing you know you're [69:17] doing this and you and write it all down [69:19] too. That's the other thing. Write down [69:21] what you're going to do and write down [69:23] how you feel and then keep doing that. [69:25] And if you could do that all the time, [69:26] you'll start developing this like [69:28] momentum that we were talking about, [69:29] right? where you're like, "Okay, I'm on [69:31] I'm on the course. I'm on a process." [69:32] >> But it doesn't have to be like you're [69:35] you're exhausted and then you go to the [69:36] lab and you're like, [69:37] >> "I can't even [ __ ] concentrate." You [69:39] know, I was doing Tabata sprints on the [69:41] air don machine. Like, this is crazy. [69:43] >> Well, that's uh it's really good advice [69:45] and I'm going to take you up on it. So, [69:47] let's say I'm lucky enough to come on [69:48] the show again. [69:49] >> Yeah. [69:49] >> I'll wear a tight t-shirt when [69:51] >> Let's go. [69:52] >> Right. [laughter] So, 20 million people, [69:54] >> you have to get off that [ __ ] goofy [69:56] plant-based diet. Well, let's speak [69:58] about that because that's one of the [69:59] things we disagree on. [70:01] >> I'm on a plant-based diet because I've [70:03] seen a lot of work on animals at least [70:06] that plants promote longevity. I eat a [70:09] lot of protein. [70:10] >> It's interesting because you're not an [70:11] animal. You know that, right? [70:12] >> I'm not a mouse. [70:13] >> You're not a mouse. [70:14] >> I'm definitely an animal, but you're [70:15] human. [70:17] >> It's the most meat is the most [70:18] nutrientdense food that's available. [70:20] >> I love meat. I'm I love meat. [70:23] >> Eat it all the time. [70:24] >> I believe it. There are two there are [70:26] two states that we can be in. [laughter] [70:30] >> I should try meat and then we can see [70:32] >> 100%. You'll feel great. [70:33] >> I've been measuring myself with rings [70:35] and blood tests for the last 20 years. [70:37] >> You should try elk. I'll get you an elk [70:39] steak. [70:40] >> I'd love to try it. Sounds good. I'm not [70:42] against meat. I will eat it. [70:43] >> You'll eat it and you'll be like [70:44] >> Yeah. Don't get me addicted to meat. [70:46] >> You feel it right away like a [groaning] [70:49] [sighs and snorts] [70:50] all your synapses start firing. Your [70:52] body starts like Yes. This is what we [70:54] wanted, David. [70:55] Well, here's here's some science. Um, [70:57] which is what I do. [70:59] >> There are two states. [71:00] >> This is my my theory. There's the [71:02] abundance mode, which is very good for [71:04] health. You'll build muscle. You'll [71:05] you'll heal better. [71:06] >> That's meat, [71:08] >> right? [71:08] >> Killed a mammoth. There's adversity [71:10] mode, which is we're out of meat. We're [71:12] going to we got to eat roots and [71:14] berries. [71:15] >> That's adversity. We got to run. [71:16] Running, exercise, eating less. That's [71:19] adversity. [71:21] >> Both are good for you. This one is pro [71:23] survival. This one is progrowth. [71:25] This one is longevity. This one is [71:27] you're going to be stronger, fitter. [71:29] >> How do you determine that though in [71:31] terms of like what is longevity versus [71:33] what is just like health and vitality [71:35] currently? [71:36] >> Well, it's based on the last 30 years of [71:38] research in a variety of animals. And [71:40] >> this doesn't have to do with the blue [71:41] zones, does it? [71:43] >> No, I'm not. [71:43] >> Cuz you know that's all horit, right? [71:45] >> Uh I I read that recently. Yeah. [71:47] >> Isn't that nuts? [71:49] >> It's a lot of it's fraud. [71:51] Well, people have been records are hard. [71:53] >> Well, it's not just hard. A lot of it is [71:55] actual fraud where people were getting [71:57] checks for their grandpa and grandpa was [71:59] dead. So, they weren't writing it into [72:01] the government. They didn't expose like [72:03] this was the problem with Okinawa in [72:05] particular [72:06] >> is that they would have to in order for [72:08] these people to get taken off the list, [72:10] they would have to inform the government [72:12] that this person died and they just [72:14] didn't do it. And so they had this list [72:16] of people that they were counting in [72:18] their census that were like so old [72:20] really like this is crazy. What are you [72:21] people doing? Was 100 years old. [72:24] >> The oldest person in the world [72:25] apparently 122. [72:26] >> There's a theory not proven that the [72:29] oldest person in the world was actually [72:31] the daughter who was faking it. [72:33] >> Ah [72:34] >> to get to get taxes or avoid taxes. I [72:36] think it was in France. I hope that [72:38] that's not true. [72:38] >> I bet it's true. People are full of [72:40] [ __ ] Well, either way, the maximum [72:42] human lifespan is around 117 18, which [72:45] is still a lot more than we live. [72:47] >> And what's really crazy is none of those [72:49] people are doing everything right. [72:50] >> Exactly. [72:51] >> They're all smoking cigarettes and [72:53] drinking wine and having a good time. [72:55] And that's a factor that we really need [72:57] to take into consideration. Loneliness, [73:00] isolation, and sadness are one of the [73:04] greatest contributors to poor health [73:06] outcomes. [73:07] >> It's number one. [73:07] >> Is it really? [73:08] >> Yeah. Robert Voldinger at Harvard had a [73:10] study for I think it was 40 years. World [73:12] War II vets, they looked at everything, [73:14] blood pressure, cholesterol. The number [73:16] one thing that predicted longevity in [73:18] those men was having a reliable partner. [73:23] >> Yeah. So, [73:24] >> not just a reliable partner, someone [73:26] that you love. [73:28] >> That's true. [73:28] >> Someone that you like want to be around [73:30] all the time. You enjoy them. You still [73:32] enjoy their company, which is possible. [73:35] Most people don't believe that's [73:36] possible. Well, you're a role model in [73:38] that. [73:38] >> I love my wife. I I have fun with her. [73:42] Like, we I've been with her for a long [73:43] I've been married for 17 years. I enjoy [73:45] her. I enjoy hanging out with her. Like, [73:47] she's cool. Like, she's a fun and I have [73:50] friends that aren't in situations like [73:52] that. And it's it's so bad when you're [73:57] like I have a friend who just we were [73:59] actually talking last night. He just got [74:01] out of a crazy relationship where he's [74:03] dating this girl for seven years. was [74:05] chaos and this and that. And I said to [74:08] him and he was like, I he's 40 and he [74:10] goes, I don't think I'm ever going to [74:12] have a relationship again. He goes, it [74:14] was so bad. He goes, being single feels [74:16] so good. And I said, there's an old [74:18] saying, it's so much better to be alone [74:21] than to wish you were alone. And he's [74:23] like, yes, that's it. Cuz he was like [74:26] with this crazy lady and he was like, I [74:29] just wish I was. And he finally got free [74:31] >> and now he's like, I I think I'm ruined. [74:33] And I'm like, it doesn't have to be like [74:35] that. You can find someone that you [74:37] actually love and you really enjoy their [74:39] time. You you enjoy being with them. [74:41] It's possible. [74:42] >> There's good people out there. [74:43] >> But you gota you got to also be someone [74:45] that that kind of person wants to be [74:47] with. [74:47] >> That's the other thing. [74:48] >> Oh, for sure. And stress of [74:50] relationship. Um, we've seen in studies [74:52] that clock with those chemicals on the [74:54] DNA, it accelerates when you're under [74:56] stress or going going through a breakup. [74:58] >> Oh, yeah. Oh, god. You see it too. Oh, [75:00] I've seen people going through divorces [75:01] and it's just like it takes decades off [75:04] of their life. They just look wrecked [75:06] >> and it takes a year or two for them to [75:08] like achieve equilibrium again. [75:10] >> It's hard. [75:11] >> It It is. It is. Uh I went through that [75:14] actually just during co when our family [75:17] got shoved in a house together and with [75:19] >> Yeah, it was brutal. It was unexpected [75:21] too. [75:22] >> Wow. That's the stress test, right? [75:24] >> It was super stress. It was super [75:26] stress. Um, funny without the pandemic, [75:28] we might have been able to make it, but [75:30] forcing us all to be in one little house [75:32] with no internet working well, it was [75:34] tough. Um, but any case, I'm I'm great [75:37] now. I'm very happy. So, but I I do know [75:40] how bad it can get and it's brutal. [75:42] >> Yeah, bad relationships can [ __ ] [75:44] wreck people. I mean, it can wreck your [75:46] health and but also it's not just [75:48] relationships in terms of your [75:50] significant other, husband, wife, [75:52] partner, whatever you want to call it, [75:53] but also bad relationships at work. Like [75:56] if you have a a tyrant for a boss and [75:59] you know and every day you're you're [76:00] getting you're you're working overtime [76:02] and you're getting yelled at and you're [76:03] you're on the phone and you're you're at [76:05] home trying to keep up with work and you [76:07] never get like that that kind of [76:10] relationship where you have like this [76:11] like antagonistic terrible relationship [76:14] with people that you work with. That's [76:16] bad too. [76:16] >> Oh for sure. [76:17] >> Your body doesn't differentiate between [76:19] romantic relationships and those kind of [76:21] relationships are almost equally bad. [76:23] >> Cortisol will be high. This will [76:25] accelerate you. I used to keep fish. Uh [76:27] I was one of those people at school and [76:30] the fish that got picked on by the [76:31] dominant fish were small, like color, [76:34] live short. [76:35] >> It's it's biology. If you're picked on [76:37] and you're stressed, you're going to age [76:39] faster. [76:40] >> Fortunately, uh I think you you're [76:41] probably the same at my age. Uh I've [76:43] managed to weed out most of the jerks [76:45] and I don't work with them at all. [76:47] >> I've got a great partner who we we have [76:48] a hobby of longevity together. [76:50] >> So that I'm I'm lucky in that regard. [76:52] Now [76:52] >> you found a new one. [76:54] Yeah, longevity specialist. Imagine [76:56] that. [76:56] >> Congratulations. Well, that's nice, too, [76:58] right? Find someone who just like thinks [76:59] the way you think and has similar likes [77:03] and interest, like you say. Yeah, that [77:04] definitely can help. Yeah, I know a lot [77:06] of my friends that are in really good [77:07] relationships, their their significant [77:10] other has the same hobby as them, you [77:12] know, like whatever it is, they both [77:15] like to climb mountains or whatever the [77:16] [ __ ] it is. Find a thing. But that [77:19] helps, too. So you actually enjoy [77:20] spending time together doing something [77:22] that you're both really excited about. [77:23] That helps too. [77:24] >> So relationships is one and the other [77:26] four major ones from that study were uh [77:29] don't smoke, don't drink, get enough [77:31] rest, um and get exercise. And that was [77:34] enough to extend by 15 years. [77:36] >> But what about those old people that [77:38] live forever and do smoke and drink? [77:40] Because that's kind of weird. [77:41] >> Well, there are 0.01%. They're not [77:43] examples of what [77:44] >> is that really what it is? [77:45] >> Yeah. It's just [77:46] >> so the majority of people who get old [77:48] and live to like centinarians like what [77:52] what are the common things that they [77:54] have? [77:55] >> Uh the big one is that they don't stress [77:57] a lot. They usually have a good sense of [77:58] humor. [78:00] >> Interesting. [78:01] >> Right. Uh they they haven't been [78:03] overweight and they say that they [78:05] typically couldn't remember when they [78:07] lost sick. [78:08] >> I wonder how much time Twitter takes off [78:10] your life. [78:13] Yeah, [laughter] [78:14] we should study that. It's already taken [78:17] a lot off mine. [78:18] >> It does. [78:19] >> And if you read the comments even more. [78:21] >> Yep. Exactly. I'm so much happier since [78:24] I swore off of all that stuff. It's just [78:26] not good for you. It's really, really [78:28] bad for you. It's also you're constantly [78:31] dealing with the problems of the whole [78:32] world, which I think is a lot for a a [78:35] human being that lives in a community in [78:38] a neighborhood. It's a that [ __ ] that's [78:40] happening over there really shouldn't be [78:43] a primary focus of your life like where [78:46] where you're in the moment actually [78:48] doing your life. It's not the same. [78:51] You're not in the same area as this [78:53] problem but yet this problem is [78:55] overwhelming. You're all day long life [78:57] >> and you're in fight or flight constantly [78:59] >> all day. All day and you're worried [79:01] about the climate. Oh my god. Like [79:03] there's so much there's so much that [79:05] freaks people out that it really [79:07] shouldn't be affecting you at all. [79:09] >> Exactly. And actually the world doesn't [79:10] change if you don't read it. So it's [79:12] it's [79:12] >> that's the key. That's the key. [79:14] >> But then you're like, well, you need [79:16] you're passing off the responsibility to [79:18] other people. You should get involved. [79:19] Like you should get involved. [laughter] [79:22] >> I'm going to be over here. [79:23] >> That's right. Well, if you focus on [79:25] doing something good and you're good at [79:26] it. [79:27] >> Yes. [79:27] >> Like yourself. I think that uh you don't [79:29] need to be doing more than that. [79:30] >> You can't focus on everything. And [79:32] anybody who tells you you can is a fool. [79:34] Or anybody who tells you what you should [79:36] or shouldn't be focusing on is a fool. [79:38] >> Yeah. A few years ago, someone uh at a [79:40] talk that I gave said, "You should be [79:42] working on climate change." [79:43] >> [ __ ] off. [79:44] >> After I cure aging, I'll get to climate [79:46] change. [79:46] >> Yeah. Why don't you go to China and tell [79:48] them to stop making coal factories? Shut [79:50] the [ __ ] up. Just shut up. You [79:53] No, you're not going to fix it. [79:55] >> Yeah. [79:56] >> Yeah. [79:57] >> Somebody is. Somebody's working on it [79:58] and that's their goal. And God bless [80:00] them. [80:01] Good luck. [80:02] >> Yeah. Well, what what I try to spend my [80:04] day is efficiently helping the world so [80:06] that people ask me why do I study aging [80:08] in the first place and it really is that [80:10] I'm trying to please my grandmother like [80:13] some of us. Uh she was the one that told [80:15] me that uh I need to make the world a [80:17] better place. And she's gone. [80:18] >> That's what she said to you. [80:20] >> When I was four, it was it's been that [80:22] ever since. She told me two things. [80:25] >> Humans are evil. She lived through World [80:26] War II in Hungary and [80:28] >> Oh, wow. the Russians came in and raped [80:30] everybody, she said. And then uh so she [80:33] escaped to Australia and then she said [80:35] that the other uh the other issue is [80:38] that uh we don't do enough as humans to [80:41] better the world. And so I had that [80:43] stuck in my mind. Um she also, by the [80:45] way, said, "Oh, we all die." And I [80:47] thought that that that's not really [80:49] fair, is it? And that set me on this [80:51] path. [80:53] >> Make the world a better place and we all [80:55] die. And you're like, "Ah." [80:58] >> And what I've noticed with my kids is [81:00] that even if you tell them that, they [81:02] they forget about it because it's brutal [81:04] to think about death every day. [81:05] >> Yeah. [81:06] >> But for some reason, it's just stuck in [81:08] my head. And every day I'm like, [81:09] "Another 150,000 people are going to die [81:11] today due to aging [snorts] related [81:14] diseases." [81:15] >> So my lab is is missionoriented. If [81:17] we're a day late with something, it's a [81:19] lot of people that are suffering [81:20] potentially uh avoidable diseases. [81:23] That's why it's sort of understandable [81:24] that people like show up outside of your [81:26] lab and like [snorts] [81:27] like I need to talk to you. [81:30] >> I need this. [81:31] >> Yeah. Blind people want to get in the [81:32] trial. It's it's big and I think if the [81:35] trial works it's going to be a very [81:36] strange world especially for my lab and [81:38] for me. Uh but we'll see. And even if it [81:41] doesn't work this time, the science is [81:44] strong enough that we'll figure it out. [81:45] We will we will do this. It's just a [81:47] question of when. And so do you think [81:49] that AI is going to have a significant [81:51] impact on the kind of improvements that [81:53] you're able to [81:54] >> It already is. We're going super fast [81:56] and AI is has revolutionized biology. [81:59] It's revolutionizing everything, of [82:00] course, but particularly in biology [82:02] where we used to have to read 15 papers [82:05] a day. Now we can read a million if we [82:07] want. It's totally different. [82:09] >> Wow. [82:11] >> Yeah. It's uh superb brain. [82:14] A 19-year-old came to my lab this summer [82:16] and the lab grows from 20 to 40 people. [82:19] And we're trying to figure out how do [82:21] these three genes reset the cell? How [82:23] does the cell remember what it was 30, [82:26] 40 years ago? Where's that information [82:28] stored in the cell? And I've got this [82:31] theory that there's some new biology. [82:34] There's a record in the DNA somewhere. [82:36] And I gave him that task. I said, "Can [82:39] you just go to the databases of the [82:41] whole world, look at all the data that's [82:43] there is exabytes of data and see if my [82:46] prediction is true or at least you can [82:48] get evidence for it." Uh, two weeks [82:50] later, he came back and the whole team, [82:52] not the whole team, but five other [82:54] people were smiling. We have to show you [82:56] something, David. Right. Come in my [82:58] office. We sat down. He shows up on the [82:59] board on this uh LCD screen. I think we [83:03] found the smoking gun for what your [83:05] theory suggests. and he used AI to [83:08] process all that data and the AI came [83:10] back and said, "Yeah, you're probably [83:12] right." And there's a 19-year-old [83:14] straight out of high school who did this [83:16] >> that did something that the whole field [83:17] and all these professors and all these [83:19] fancy sirs could not figure out until [83:22] now. [83:24] >> That is phenomenal. [83:26] That's so promising. It's so exciting. [83:28] >> It is. I mean, the future really does [83:30] belong to people who can wrangle AI even [83:32] on their phone. I think people on their [83:34] phones are going to be making medicines [83:36] or at least designing them [83:37] >> or bombs. [83:38] >> That's the problem. And [laughter] [83:40] bioweapons, right? And you recently had [83:43] uh was it Anna on the show to talk about [83:45] bio weapons and this kind of stuff. [83:47] >> Uh that is a big big worry. I actually [83:49] had to disclose to the US government [83:50] when I first got here that I did have [83:52] the capability of making a boweapon. [83:54] >> The the Annie Jacobson episode uh that [83:56] we just did on bioweapons was absolutely [83:58] terrifying. Yeah. She's I mean she [84:02] scared the [ __ ] out of the world with [84:03] her nuclear war book and now she's [84:05] scaring everybody with her bioweapons [84:07] book. [84:08] >> Yeah. [84:08] >> Yeah. That's scary. [84:09] >> It is. Uh what what I've got is a [84:11] database of all known pathogens and new [84:13] ones that could come. So I'm trying to [84:15] do my bit there to help the world if it [84:17] happens again. Pandemic or something [84:20] unnatural. [84:21] >> Yeah. Well, that would be I mean, when [84:24] you think about diseases that people get [84:26] that just like wreck their entire body, [84:29] if you really do have an original copy [84:32] somewhere in their genome of what they [84:34] look like as a healthy person, and you [84:37] could switch that back on with a factory [84:39] reboot. [84:41] I mean, we could potentially get rid of [84:44] all diseases, which is just bananas. [84:47] >> And injuries or fix injuries, grow new [84:50] limbs potentially. There's a new paper [84:52] that just came out a few days ago that [84:54] showed that the tips of the fingers of [84:56] baby mice can be coaxed once they've [84:59] healed over as a stub to regrow part of [85:02] the finger. The [85:03] >> Haven't people done that before? [85:05] >> Uh yeah, they found just two factors [85:07] were enough. So, it's not that hard. The [85:10] point is we've got the instructions to [85:12] be young and to regrow body parts in our [85:14] body. We just don't use them. [85:17] >> That's nuts. So like a salamander can [85:19] grow an extra leg or a leg that gets [85:21] chopped off. [85:22] >> Yeah, I believe we still have that [85:23] capability. We just don't use it. It [85:26] just didn't make sense to regrow a limb. [85:27] It was quicker and safer to just heal it [85:29] over as a stub and move on. But [85:31] salamanders, which get their limbs [85:32] presumably eaten pretty often, maintain [85:35] that ability. uh so give us you know if [85:39] I wouldn't say that we could evolve this [85:40] but I think using a combination of our [85:43] technology plus this new technology that [85:45] we're seeing come out where these two [85:47] factors can grow new limbs I don't see a [85:49] reason why we can't become like a [85:50] deadpool where injury doesn't hurt us [85:53] aging can't hurt us and we can regrow [85:55] body parts [85:56] >> how far do you think we are away from [85:58] being able to regrow body parts [86:00] >> oh I mean realistically probably a [86:02] couple of decades but I I've seen enough [86:04] >> that's not that far [86:05] >> seen enough to know that it's doable. [86:07] >> Couple of decades ago was 2006. [86:10] >> Well, things are going super fast. I [86:12] mean, 10 years ago, we didn't even know [86:13] aging was reversible. And now it's in [86:15] humans. [86:17] >> That's nuts. Think of that. Well, 2019 [86:21] came here, there was no AI, [86:23] >> right? [86:23] >> 2019, it was an idea that we had just [86:27] got the result in mice and I divulged [86:29] that to the world. Then it was published [86:32] uh and then we're in humans now. So if [86:34] it works then you know it's going to be [86:36] a very different world. [86:37] >> And you you feel very confidently that [86:41] some of this stuff is going to work. [86:43] >> Well it's going to work. I don't know if [86:46] this trial is going to be successful but [86:48] there's going to be a lot of people [86:49] doing these trials. I have some [86:51] competition now. Do you know about that? [86:53] >> No. [86:54] >> Uh so since I started my company life [86:56] biosciences which is doing the trials in [86:58] with ER 100 others have jump joined in [87:01] in the party. Uh so Jeff Bezos and [87:04] others have started Eltos Pharma. Um [87:07] they are based in three cities around [87:09] the world. They have a few billion [87:10] dollars to catch up. Um Sam Oldman has [87:14] Retrobio [87:16] and uh let's see, Brian Armstrong from [87:19] Coinbase, the CEO, started one called [87:22] New Limit, and they've got a lot of [87:24] money, all billions. [87:27] >> Do you think it's good that there's all [87:28] these people involved in this? [87:29] >> Oh, well competition. [87:31] >> Yeah. Yeah. I'm not doing this for my [87:33] own personal benefit. I want humanity to [87:35] be changed the way it could be. [87:37] >> And the more people like Jeff Bezos, the [87:39] more people with a large bank account [87:40] that are invested in this, the better. [87:42] >> Fantastic. [87:43] >> And of course, a guy like Bezos, he's [87:44] balling out of control, why wouldn't he [87:45] want to live forever? [87:46] >> Well, what's left if you've got [87:48] everything else, you know? Well, also [87:49] it's like it's like if you've got the [87:52] amount of money that he has and you can [87:54] tackle all these different issues, you [87:55] know, like his space program that he's [87:57] working on, all all these different [87:58] things, like of course, why wouldn't you [88:00] want to do cool things? Like, what's [88:01] cooler than being able to grow limbs? [88:04] >> Yeah. Yeah. [88:04] >> You know, what's cooler than being able [88:05] to cure all diseases and reverse aging? [88:08] >> Well, there's I don't think there's much [88:10] cooler that that's why I'm doing it cuz [88:12] that I think can be the biggest gift to [88:14] humanity is what you just said. So, I [88:16] don't know if I'll achieve it. probably [88:18] not in my lifetime, but at least I've [88:20] moved the needle and pushed the ball [88:21] ball globally in that direction. [88:24] I wonder if we're going to get to a [88:25] point in time where we can engineer [88:27] consciousness [88:28] in in terms of like find out like you [88:31] find out someone's a sociopath, you find [88:33] out someone's a kleptomaniac or [88:36] someone's an arsonist, like what [88:38] whatever it is, like if you could figure [88:40] out like what these little flaws are in [88:43] the way the mind works. If you can [88:44] completely map it out and go, "Oh, this [88:48] is the error. This is where you you're [88:50] not making these two connections." [88:51] >> Of course. Of course. This is all just [88:52] biology and engineering. There's nothing [88:54] that stops us. And this is the century [88:56] that we are able to control our own [88:58] biology. [89:00] >> Starting with cancer, heart disease, and [89:02] aging. [89:03] >> A true utopian world of peaceful people [89:06] in harmony, but healthy, [89:08] >> not peaceful. [89:09] >> I don't think world peace I think curing [89:11] aging is easier than world peace. [89:13] >> Well, if everybody achieved a state of [89:16] consciousness that allowed them to [89:18] understand that we're all in this [89:19] together. [89:21] >> Yeah. How do we do that? [89:22] >> Mushrooms. [89:24] >> Yeah. Well, there are there are certain [89:26] companies working on this. [89:27] >> I know. That's what's interesting, [89:29] right? Like Eli Liy is involved in [89:31] pharmaceuticals. Uh well, the [89:33] pharmaceutical company rather is [89:34] involved in psychedelics. [89:35] >> They just bought a tie for [89:37] >> I think it was like $3.8 billion. So, [89:39] they're all in with real capital. [89:41] >> Yeah. [89:41] >> I love it. [89:42] >> Yeah. Me, too. [89:43] >> That's great. [89:43] >> I love that they're doing that. We need [89:44] more of that. There's too much [89:46] depression [89:46] >> and anxiety in the world [89:48] >> and drug addiction. I mean, that's why I [89:50] went to the White House and got pre the [89:52] president to get involved in this [89:54] executive order on Ibagane. [89:56] >> Yes. [89:56] >> Because I've talked to so many people [89:59] that have had their life completely [90:01] turned around with Ibagane. so many [90:03] people that were uh opioid addiction and [90:06] also brain injuries, oddly enough, brain [90:09] injuries, all all sorts of TBI and CTE [90:13] that they've had like phenomenal results [90:16] from this bogatry, you know, which is so [90:20] crazy that this thing had been around [90:22] for so long and is a schedule one [90:25] substance in the United States for no [90:26] reason whatsoever. There's no risk of [90:29] addiction. There is no recreational use [90:31] of it. It's a horrible experience. I've [90:34] not not done it, but apparently it's [90:35] [ __ ] terrible and it lasts for like [90:37] 24 hours. Like, no one's going to be [90:39] doing that for funsies, [90:40] >> right? Well, the question I think that [90:42] comes up with all of these drugs is, do [90:44] you have to have the trip and experience [90:46] the craziness [90:47] >> to get the benefit? [90:48] >> To get the benefit. And I don't think [90:50] so. I think you should be able to [90:51] separate. [90:51] >> Well, you know, they've actually figured [90:53] this out with LSD. [90:54] >> Yeah. [90:55] >> Right. Do you know about this? Okay. So [90:57] they've engineered a a different version [91:00] of LSD that doesn't give you the [91:03] hallucinogenic effects but does give you [91:06] the the benefits in terms of like the [91:08] cognitive effects. [91:09] >> The at guys or someone else. [sighs] [91:11] >> I don't know what company has done this. [91:14] See if you can find that Jamie. [91:15] >> I think it might be a tie. [91:16] >> But what they've they've essentially [91:18] done and I think it's it's basically in [91:21] the lab work stage right now. I don't [91:23] think that's applied to humans yet. But [91:24] what they've done is engineered a [91:27] version of LSD that has all the positive [91:30] effects that LSD has in terms of like uh [91:33] introspection, [91:35] being able to like rethink and remap and [91:38] reset the way you view things, but [91:40] without like watching people's face melt [91:43] and thinking that demons are eating you [91:45] and all the the weird stuff that comes [91:47] with [91:47] >> it. Outstanding. It it it should happen [91:49] with with psychedelics the way it's [91:51] happened with all medicines, right? We [91:53] start with [91:53] >> something from the bark of a willow tree [91:55] and then we have aspirin, [91:56] >> right? [91:58] >> We're not eating bark anymore, [92:00] >> right? But sometimes the bark is the [92:02] really way the way to go, [laughter] [92:04] >> right? Unfortunately, sometimes that's [92:06] the part of the problem is these [92:07] pharmaceutical drug companies, they [92:09] patent these natural compounds and you [92:12] know use petroleum based synthetic [92:15] methods of creating these medications [92:18] now that they can sell and profit wildly [92:20] off of. Whereas really the best way to [92:23] do it is actually to get the plant. [92:25] >> It's true that there's the whole issue [92:27] though that if it's not approved, then [92:30] it's the wild west. You don't know what [92:31] you're getting, [92:32] >> right? That's true, too. [92:34] >> We need a middle ground. We need [92:35] something you can get fast on the market [92:37] that's known to be safe. [92:38] >> So, what we're going to need is mind [92:40] reading [92:41] >> cuz we need to know if people are full [92:43] of [ __ ] [92:43] >> That's what we're going to need. We're [92:44] going to need [92:45] >> got to work on that. [92:46] >> Yes. I think that's that's going to [92:48] change humanity more than anything. I [92:50] think you've got a good [ __ ] [92:51] detector. [92:52] >> It's okay. There's a few people that [92:54] have snuck through, unfortunately. You [92:56] know, some people they get through and [92:57] they're like, it takes a while and [92:59] you're like, uh [ __ ] [93:01] >> they're never coming back on the show. [93:02] >> Yeah. Well, there's that. It's the the [93:05] show, you know, you you learn a lot from [93:07] a person in about 3 hours. You know, you [93:10] can kind of after a while you can kind [93:12] of see little things and you have to be [93:14] forgiving and you know, you have to be [93:16] charitable and some people are just [93:18] nervous and they misstate things or they [93:21] exaggerate things or they forget [93:23] something, they get it wrong. But then [93:24] there's people that are just essentially [93:27] they really don't care about anybody but [93:30] themselves. And some of those people are [93:32] really good at pretending to be people. [93:34] They're really good at pretending, [93:36] >> you know. They're really good at [93:37] pretending to be like a normal person. [93:40] Oh, here's the LSG. LSD thing. [93:42] Researchers recently engineered an LSD [93:44] analog called, how do you say it? Plus [93:47] minus JRT that appears to keep many of [93:51] the LSD's brain beneficial and cognitive [93:53] effects while dramatically reducing and [93:55] possibly eliminating its hallucinogenic [93:57] trip in animal studies. So, it's almost [94:00] the same molecule as LSD, but scientists [94:02] swap the positions of just two atoms in [94:05] the structure. The subtle change makes [94:07] JRT bind more selectively to serotonin [94:10] receptors in a way that promotes [94:11] neuroplasticity, growth, and repair of [94:13] synapses, but minimizes hallucinogenic [94:16] signaling. That is that's incredible. [94:20] Anti-depressant. Look at this. [94:22] Strong anti-depressant effects at doses [94:24] reported to be around 100 times more [94:27] potent than ketamine in standard rodent [94:29] tests. Cognitive benefits. Improved [94:32] cognitive flexibility and performance in [94:35] tasks modeling the negative and [94:37] cognitive symptoms of schizophrenia. [94:39] Holy [ __ ] That's incredible. [94:43] When when and where do we get it? [94:45] >> Well, I think it's fairly recent. [94:46] >> Yeah, it's at a UC Davis study. They [94:49] just developed it. uh it's in mind. [94:51] >> Shout out to our AI sponsor Perplexity [94:53] for providing us with this information. [94:55] This is again I mean like we could just [94:56] get this information now through AI. [94:58] Like I mean this that AI for our show [95:01] has been gigantic. I mean just the [95:03] ability to just ask it a question [95:06] instead of Google searching and have to [95:07] go through all these different [ __ ] [95:08] articles. What does it say? What is [95:10] that? Who's right? What's this one? [95:12] What's the website? You just ask AI and [95:15] perplexity just gives us all the [95:17] information. So, uh, proceedings from [95:19] National Academy of Science researchers [95:21] at California of San Diego Davis, uh, [95:24] excuse me, Cal University of California [95:26] Davis, uh, reported the creation of JRT, [95:29] chemically modified version of LSD. So, [95:31] this is like what year? [95:36] >> So, 2025. So, last year. [95:38] >> So, [95:38] >> so it's exciting. [95:39] >> Five years away, but still, you're [95:41] right. [95:41] >> Is that that the timeline? [95:42] >> Uh, at a minimum, usually it takes that [95:44] long. Uh, but that's exciting. At least [95:46] the principle is there that you don't [95:47] need to listen. [95:48] >> Well, how about for schizophrenia? [95:49] That's incredible. Yeah. I mean, that [95:51] that is incredible because that is one [95:53] of the saddest things to watch somebody [95:55] fall into the grips of schizophrenia. [95:57] >> Yeah. [95:57] >> I've seen people fall in and come out, [95:59] which is interesting. [96:01] >> I thought for the [ __ ] detector, we [96:03] could have an AI that that either dings [96:04] or has a green or a red on your [96:07] forehead. [96:07] >> I'm pretty good at it, but I think no [96:09] one's no one's perfect at it. And I [96:11] think ultimately if we get to a place [96:14] whether it's a a technological [96:16] innovation or or what have you where we [96:19] can actually read the contents of [96:21] someone's thoughts. I don't think that's [96:23] outside the realm of possibility. [96:26] [sighs] [96:26] >> You'd need an implant, I think. But [96:28] >> Elon says the Neurolink's going to be [96:30] able to pull that off. [96:31] >> Yeah. [96:31] >> Oh, you're going to be able to talk [96:33] without using words. [96:35] >> Like what? I think he's right, though. I [96:38] think if we all like lock into a hive [96:41] mind and uh and then if we develop like [96:46] through AI, if we develop a universal [96:48] language worldwide, [96:51] >> well, we already have that. [96:53] >> What do we have? [96:54] >> Well, the new headphones from a big [96:55] company that I won't name, you can [96:57] translate. [96:58] >> Translate. Yes, translate. But it's [97:00] translating to English if we just all [97:02] The problem with that is there's [97:04] context. There's all sorts of different [97:06] things that other cultures, different [97:08] languages, they they when it's [97:10] deciphered and changed and translated [97:11] into English, you lose a lot of the [97:13] meaning and the the context is weird. [97:16] >> If we develop a universal language, [97:19] >> that would be ideal. Uh, English is a [97:21] good substitute. I was shocked. I'm I'm [97:23] always shocked traveling globally how [97:25] many people can just speak English now. [97:26] >> Yeah, it's pretty amazing cuz America [97:28] rules. You're welcome. [97:31] >> Well, we have to thank Britain for that. [97:33] [laughter] America should say you're [97:34] welcome. [97:35] >> Yeah, they they they were they were [97:36] cute. They did a good job of starting it [97:38] out, but we took the ball and [97:40] >> started all over the world. [97:41] >> So, who's next? China. [97:43] >> God, I hope not. I don't want to learn [97:44] Chinese. That's too hard. All the [97:46] [ __ ] characters. That's ridiculous. [97:47] Even people that I know that could speak [97:48] Mandrin, they can't write it, [97:51] >> you know, to like to get to that level. [97:52] I have a couple friends that speak [97:54] fluent Mandarin and they can't write it. [97:57] >> Writing is [97:58] >> Yeah. Well, the the students in my lab [98:00] who come from China, um they're being [98:02] picked on by by the uh immigration, but [98:04] they don't want to go home. They love it [98:06] here. [98:07] >> I'm sure because they're stealing all [98:08] your secrets and bring it back home. [98:09] >> There's that. There's a lot of [98:10] regulation on that now as a scientist. [98:12] Oh, yeah. Do you know that? Yeah. [98:13] >> Oh, I could imagine. Yeah. I mean, it [98:15] has to be because that is an actual real [98:17] threat. [98:18] >> Exactly. So, the people that come [98:19] through my lab have to be vetted now, [98:21] >> right? But the people that come over [98:22] here and experience the kind of freedom [98:24] that you have in America. [98:25] >> Oh, yeah. I came here from Australia. [98:27] Australia is pretty free, but compared [98:28] to Australia, America is so different. [98:30] >> Yeah. [98:31] >> I can't go back. [98:33] >> What's the big difference? [98:35] >> That I feel I can do anything I want if [98:37] I just put my mind to it. There's not [98:40] social barriers. There's not monetary [98:41] barriers. At least for a white male like [98:44] me who's got a degree. I know it's not [98:46] for everybody, but I feel like if I want [98:48] to start a company, I've got a great [98:50] idea. I can do that here. Fat chance [98:52] you'll do that in Australia. People [98:54] aren't willing to invest in great ideas [98:56] down there. Not not often. [98:58] >> That's a bummer. Do you think that [98:59] changes anytime soon? [99:01] >> No. You the US is so unique. There's a [99:04] lot of money flowing. People are willing [99:06] to place a bet and even lose the money. [99:08] That's rare. Australians, most of the [99:10] world, if not all, people are scared to [99:12] lose their money if they have it. Here, [99:14] it's like, okay, I risked it. I helped [99:16] the world. I feel good. [99:18] >> It's a very generous country. Very. And [99:21] I love it here. It's when I arrived [99:22] here, I just felt, ah, I'm home. I love [99:25] hearing that from people that have come [99:26] from somewhere else because it kind of [99:27] reaffirms why uh people in America are [99:31] so proud of what this country is. [99:33] >> Should be. Yeah. [99:34] >> And that's why it bums me out where [99:35] people are so mad at America in terms of [99:38] I I get look in terms of foreign policy [99:40] and some of the things that are wrong [99:41] with America, but just in overall this [99:44] experiment in self-government is pretty [99:46] remarkable. [99:47] >> Yeah. Yeah, I watched the TV show. Was [99:49] it the American Experiment? Uh, came out [99:52] for the anniversary of 250th. [99:54] >> I haven't seen it. [99:55] >> You got to see it. [99:56] >> What's it on? [99:57] >> Uh, it's it's the founding fathers and [99:58] their lives and how they were fighting [100:00] and what what was going on behind the [100:02] scenes. [100:03] >> They were just young kids. They're in [100:04] their 20s, 30s. [100:05] >> I know. Isn't that nuts? [100:06] >> Yeah. Just Benjamin Franklin was the old [100:08] dude, but they were so young. But but [100:10] they were they were in the middle of it. [100:13] They kind of realized they were making [100:14] history, but so many things could have [100:17] gone wrong. We would not have had the [100:19] United States if just a few votes went [100:21] one way or the other [100:22] >> and a few wars. [100:23] >> Yeah. [100:23] >> A few of the different battles that they [100:26] >> Exactly. The US was losing the war [100:28] against Britain badly. [100:30] >> Yeah. They [100:32] Yeah. [100:32] >> Yeah. We don't thank the French enough, [100:34] actually. [100:34] >> I know, right? Somehow they became our [100:37] enemy. [100:37] >> Yeah. Remember during the the Gulf War [100:40] they turned French fries into freedom [100:42] fries because people hated the French? [100:43] >> Yeah, but everyone hates the French [100:45] because they're so arrogant. [100:47] >> Sorry French. I have some friends who [100:48] are good good friends of French. [100:50] >> I think generally when people are [100:51] arrogant it's because they did something [100:52] [ __ ] awesome. [100:54] >> Well, in the 1800s they did. Yeah, [100:56] >> they conquered [clears throat] Europe. [100:58] >> Not not sure if that's awesome. [101:00] >> Here's a fun perplexia search I just [101:01] did. I said, "Do Americans have a risk [101:03] gene in [101:04] >> a risk gene? One of the best studied [101:06] variants in the dopamine receptor gene [101:08] DRD4, [101:10] specifically the seven repeat 7R version [101:13] is associated in some studies with [101:15] novelty seeking, impulsivity, and higher [101:18] financial or social risktaking. I wonder [101:21] if I have that gene for sure. This seven [101:24] probably not. Who knows? The 7R variant [101:27] is unevenly distributed around the [101:29] world. Its populations in populations [101:31] across the Americas, it shows up in [101:32] roughly 48% of chromosomes studied. [101:34] While in East Asia, it's found in only [101:36] about 2%. [101:38] >> Wow. [101:38] >> Whoa, that's crazy. [101:41] >> It all comes down to genetics. [101:43] >> Evolutionary work suggest it became more [101:44] common in groups that migrated further [101:46] after leaving Africa. And those lineages [101:49] are strongly represented in the Americas [101:51] today. [101:52] >> That actually I was thinking of the [101:55] people that you know had the balls to [101:57] [ __ ] come here. Now were your balls. [101:59] You don't have to do that much, but you [102:01] can still have balls to gamble and take [102:04] risks. And [102:05] >> that must be But then Australians should [102:06] have it. [102:07] >> That completely Well, sort of. You guys [102:09] got forced there. Like they they moved [102:11] everybody over there because they were [102:12] criminals, [102:13] >> right? This this DDR gene uh that you [102:16] just saw, the uh was it DDR4? [102:18] >> Uh I know a bit about it because I'm [102:20] writing it in in my next book. DRD4. [102:22] Thanks, Jamie. Um, I call this the FU [102:25] gene because I'm trying to figure out [102:27] what makes humans special over other [102:29] animals. [102:30] >> And this is one of them that we are [102:33] seekers of explorers. And uh, it's it [102:36] turns out turns out that this gene is [102:38] turned on in teenagers. It gets [102:40] eventually switched off. Not totally, [102:43] but that might be why teenagers say FU [102:46] to their parents. [102:47] >> Yeah. [102:47] >> But it's a way genetically to get them [102:49] out of the nest. Like, oh, I can't stand [102:51] these parents. They suck. They're [102:52] idiots. I'm out of here. That's in this [102:54] in this gene. [102:57] Well, it's also um [103:00] I as a parent have been very aware of [103:04] not doing that to my kids, like not [103:06] forcing them into something that they [103:07] don't want to do or pushing them in any [103:10] general direction, but rather [103:12] encouraging them to seek out their [103:14] interests and encouraging them to just [103:16] like take ch and if I ever correct them, [103:19] if I ever get upset about something, one [103:21] of the first things that I tell them is [103:22] I've done all everything that you've [103:24] done. I've made every mistake. I've I've [103:26] [ __ ] up. I'm You're You're smarter [103:28] than me. I've [ __ ] up everything. I've [103:31] lied to my parents. I lied to teachers. [103:33] I [103:34] >> I've done everything that you're doing. [103:36] So, it's this is not a unique thing. I'm [103:38] just telling you from my own personal [103:40] experience and my perspective, this is [103:42] why I think cuz I love you and I want [103:44] you to do well in life and I I just want [103:46] you to recognize this. And that's how I [103:49] correct my kids. [103:50] >> I love that. [103:51] >> It's never like you listen to me cuz I'm [103:52] your father. There's none of that [ __ ] [103:54] >> Yeah. The old way we were raised doesn't [103:56] work. [103:57] >> No. And it makes you resentment, but [103:59] also probably makes you want to do [104:01] better than your parents. So, it like [104:03] motivates you in a certain way. Like my [104:05] parents were not risktakers at all. And [104:08] my whole life I've been like a wild risk [104:09] taker. That's [104:10] >> really same. Yeah. I I was resentful [104:12] that my father didn't have enough [104:14] ambition. Now he's a great guy. We're [104:16] we're best friends actually. It's been [104:17] the greatest thing for for me. But uh [104:19] one of the things I did with my kids, [104:20] you reminded me, is uh he's 19. Um, he's [104:23] a well-built guy because we were going [104:25] to the gym for a number of years. I've [104:27] tried to train him in health, but he he [104:30] spent the summer with me. He's literally [104:31] still working for me this summer to help [104:34] with the podcast and the magazine we're [104:36] about to launch. And Benjamin's his [104:38] name. He's the best kid. But he slacked [104:40] off. He was like, "Ben, I put you in [104:42] charge of social media. You haven't [104:44] posted in a week. What's going on?" [104:46] Well, you know, I slept in blah blah. [104:47] So, I had to think, am I going to get [104:49] mad at him like I would a normal [104:50] employee, or do I treat him differently? [104:53] and I decided to treat him differently, [104:55] probably because he's my son, but I [104:57] didn't want to ruin ruin the [104:58] relationship. But what I did was I said, [105:01] you know, I really think you can do [105:04] better. I think everything you've done, [105:06] the weightlifting, the the calculus, [105:09] you're amazing, but in this you're not. [105:12] So, what's going on? And it worked. We [105:15] become closer. He's really into it. He's [105:18] doing a good job now. [105:19] >> That's great. [105:19] >> So, that's the way to do it. I think you [105:21] can't be too hard on them. Can't say you [105:23] [ __ ] up. [105:24] >> Yeah. I mean, that kind of can work, but [105:26] it's a blunt instrument and it doesn't [105:29] work on everybody. And it also develops [105:31] resentment and and they also they they [105:34] miss out on experiencing your [105:37] perspective as a like for them to [105:40] understand that you are just a person [105:42] who's lived longer than them and that [105:44] you can help them navigate this road. [105:47] >> Yeah. So, you don't have to make the [105:48] same mistakes that we did. And that [105:51] that's why you're helping them. You're [105:53] talking to them about this not because [105:56] >> you're just a mean dad who likes to [105:58] [ __ ] tell the kids what to do cuz [106:00] we've all experienced that. I mean, I [106:01] had friends growing up with fathers who [106:03] [ __ ] scream at them and throw things [106:05] and and beat them and it's like, God. [106:09] And then you just grow up [ __ ] [106:11] traumatized and always resentful and [106:13] angry instead of just recognizing that [106:17] like, oh, I'm so fortunate that my [106:20] parents have this perspective where they [106:23] can explain to me why I'm going through [106:25] what I'm going through and how they got [106:27] through it. [106:28] >> Like a mentor. You're not their best [106:30] friend. You're their mentor. [106:31] >> Yes. [106:32] >> Best friend doesn't work either. [106:33] >> No, that doesn't work either because [106:35] that just allows too much shenanigans. [106:37] You know, you have to have some rules, [106:38] you know, you have to have some some [106:40] sort of regulations. [106:41] >> Yeah. [106:41] >> But you also [106:42] >> Your kids turned out well. [106:44] >> What's that? [106:44] >> How'd your kids turn out? [106:45] >> Oh, they're great. [106:45] >> Great. [106:46] >> I'm so so lucky. So [ __ ] lucky. I [106:49] mean, I I'm feel so fortunate. They're [106:51] so smart [106:52] >> and ambitious and driven and so it's [106:54] wild. It's wild to watch, you know, and [106:56] talented [106:57] >> and it's um and also like we never went [107:00] through that period where um they hit [107:03] teenage years and they hate you [107:05] >> like that. I experienced that. [107:07] >> God, that's so nice. I mean, my [107:10] youngest, she get upset at me sometimes [107:11] about certain things, but she bounces [107:13] back quickly. It's never like some kids [107:15] where they just grow to hate their [107:17] parents. Like [107:18] >> the RD4 gene, uh, maybe they don't have [107:21] strong one. [107:21] >> I don't know about that. I think it's [107:24] how you communicate with them. I really [107:26] do. I think that's a big factor. You [107:28] have to communicate with them like you [107:31] truly care about their development. And [107:33] the most important thing I think the [107:36] most important thing I think is that I [107:38] always tell them whatever you've done [107:39] what whatever mistake you've made. I [107:41] made way worse mistakes. I was like I am [107:43] not coming at you from a a flawless [107:45] person you know. I'm not coming at you [107:47] from the perspective of someone who like [107:50] you're an idiot. I figured that out. You [107:52] should figure it out. Like no. I [107:55] whenever they from the time they were [107:56] really little anytime I had to correct [107:58] them I said I did everything that you're [108:01] doing. everything. [108:03] >> I I threw my food on the floor, too. [108:05] >> Yes. All All the above. Whatever [ __ ] [108:08] stupid thing you've done as a kid, I [108:10] guarantee you [108:11] >> that is great advice. Really great [108:13] advice. So, I I hope everyone listening [108:15] hears that because I I actually had to [108:17] learn the hard way. My first kid, I did [108:19] what my parents did, which was you can't [108:21] say that. [108:22] >> Yeah. [108:22] >> And my first is a lot more rebellious [108:24] and distant than my third, for that [108:26] reason. [108:26] >> Isn't that interesting? Yeah. [108:28] >> Yeah. It It actually is really true. [108:29] I've seen it. [108:30] >> Yeah. And it's I thought it was going to [108:31] kill their motivation, but it doesn't at [108:33] all. Well, I thought like, you know, [108:35] making things easy for them and not [108:37] being strict. Like maybe it's good to be [108:39] strict cuz then you just have this [108:40] determination to I'll show everybody. I [108:43] don't think that was my thing as a [108:45] child. Like I'll [ __ ] show you. But I [108:47] don't think everybody needs that. I [108:49] think you you're much better off having [108:51] a healthy relationship with ambition [108:54] where you're excited about things [108:56] because you're passionate about them and [108:58] you you find [109:00] great reward in being creative or being [109:03] enthusiastic about something. [109:05] >> Exactly. And and open their eyes to the [109:07] world that exists. [109:08] >> Yes. [109:09] >> You know, we used to do work experience. [109:10] You go and do a job and that's your work [109:12] experience. [109:13] >> The reason I wanted my son Ben to work [109:14] with me is he can see how what it's like [109:16] to be an entrepreneur and [109:18] >> build something and and be excited and [109:20] work is super fun. Get into it. [109:22] >> Uh I think a lot of kids just don't get [109:24] that experience. They don't know what's [109:25] possible [109:26] >> and just showing them the world is what [109:28] we can do as parents. [109:30] >> That's awesome. Yeah. And you know, I [109:33] mean, [109:34] >> some people don't have that at home, [109:35] unfortunately. But that's one of the [109:37] cool things about the world that we live [109:39] in is that kids today have access to so [109:43] many different perspectives now because [109:45] of the internet. There's so many [109:47] different podcasts and YouTube [109:49] conversations and different things where [109:51] they can just take a little tool from [109:54] that. Just take a little piece from that [109:56] and apply it to the way they interact [109:58] with the world. [109:59] >> Yeah. Um, for sure. And I would [110:02] encourage parents to give their kids [110:05] stuff to read. [110:06] >> We talked about social media, how that's [110:08] just addictive. I saw how my kids wanted [110:11] to just scroll through their phones then [110:13] then read. And if they can't read a [110:15] book, give them a magazine. I subscribe [110:18] to Nat Geo, National Geographic for my [110:21] kids. And I think get them used to [110:23] reading because it's going to be a lost [110:25] art if we don't. [110:27] >> I know. Isn't that nuts? [110:29] >> I I maybe read 10% of the things that I [110:31] consume. I I consume so much in audio. [110:35] uh just for time reasons because there's [110:38] so much there's so much time where I'm [110:40] driving my car or I'm working out or I'm [110:42] in the sauna or I'm in the hyperaric [110:45] chamber or I'm in the red light therapy [110:47] >> that's reading three are re [110:48] >> it is similar but I think it's only like [110:52] 70% of reading [110:54] >> I don't think it's 100% I don't think [110:55] you get the full effect but it's still [110:57] way better than not doing it [110:59] >> you know but I'm I'm aware that like [111:01] sitting there concentrating actually [111:03] reading a book without hearing hearing [111:04] another person's voice talking. There's [111:07] another mechanism. There's another thing [111:08] that's going on that's uh it's a [111:10] different way you interact with the [111:12] material whether it's non-fiction or [111:13] fiction. [111:14] >> Yeah. I I like the fact that I can [111:16] listen to you and I'm doing something [111:17] else and I have to sit down, [111:19] >> can move, go for a walk. [111:20] >> Yeah, that's for me it's it's just I'm I [111:24] have too many interests. I have way too [111:26] many things that I do. So, it's very [111:28] hard for me to just allocate a certain [111:30] amount of time to sit there in silence [111:32] and read. Yeah, I use reading to fall [111:34] asleep. That's a good way. [111:35] >> It does do that, right? That's kind of [111:37] nuts how well it does that. [111:38] >> Yeah. Although I am finding it's harder [111:40] to read now that my eyes aren't young. [111:43] Need some of my uh jeans myself. [111:46] >> I've tried that. Does it work for you? [111:48] >> Oh, yeah. Oh, I mean people are [111:50] skeptical about this and they think I'm [111:52] full of [ __ ] No, I don't need reading [111:55] glasses anymore. [111:56] >> Really? [111:56] >> Yes. I had reading I always have these [111:58] [ __ ] things laying around. I don't [112:00] even use them anymore. [112:01] >> That's awesome. Yeah, there's a lot of [112:02] science now for red light. [112:05] >> I can tell you as a regular user for [112:08] multiple years, [112:09] >> it took a while. It took like I was [112:12] waiting for it in the beginning like [112:13] what the [ __ ] And in fact, and not only [112:15] that, in the beginning, because I don't [112:17] close my eyes in the red light bed. I [112:19] thought it was making things blurriier. [112:21] I was like, "Oh my god, am I [ __ ] up [112:23] my eyesight like listening to these [112:24] assholes?" Uh, but no, it just took a [112:27] while. And then over the course of like [112:30] many months, I started seeing some small [112:32] improvements. And then I started seeing [112:35] some pretty big improvements over the [112:36] course of about a year. Whereas now I I [112:40] it's not my eyes aren't perfect. They [112:42] aren't like they were when I was 20. But [112:44] they are way better than they were when [112:46] I was 50. [112:47] >> How often did you have to do that? [112:49] >> I do it three times a week minimum. [112:51] That's what I try to do. But sometimes [112:52] I'll do it five days a week. I just get [112:54] in there and it's 20 minutes. I lay in a [112:56] light bed, close my eyes, open my eyes, [112:58] whatever. It seems to work on your [113:01] vision even if you wear a blindfold. [113:03] >> What about people that can't afford a [113:05] bed? Can you get little devices? [113:06] >> Yes, you can get Well, there's a company [113:07] called is it's called JV, right? J UV. [113:12] Is that the name of the company? They [113:13] were our sponsor at one point in time. [113:15] That's how I started it. They had uh [113:17] it's just a light panel that you stand [113:20] in front of those. Yeah. [113:22] >> And that that works too. that. Um, but [113:25] this one, the one that I got a red and [113:28] near infrared light therapy devices, [113:31] JWV, J O O VV, medical grade light [113:35] therapy devices. Uh, I had one of those [113:37] and that's when I started seeing [113:38] benefits, [113:39] >> but the um the big one that I got I got [113:43] from Gary Brea from his company and it's [113:45] it's a like a [ __ ] tanning bed and [113:47] you lie in it and that one's amazing but [113:49] that's expensive but I don't think you [113:51] have to have that for that those kind of [113:52] improvements. also improves collagen, [113:54] your skin, makes you look better and um [113:58] the but for me the most obvious and [114:00] profound was the improvement in my [114:02] vision. [114:03] >> Well, it makes sense. The the science [114:05] behind red light wasn't there 10 years [114:06] ago and people were questioning it. But [114:08] now we know if you shine certain [114:10] wavelengths like near infrared on cells, [114:14] >> the mitochondria, which are important [114:15] for reversing aging or slowing it [114:17] >> get revved up. Um it's actually related [114:20] to Viagra. long story but Viagra and red [114:24] light have something is in common and it [114:26] does help mitochondria and that's very [114:28] important for the eye the mitochondria [114:29] actually the most important in any part [114:31] of your body uh the eye is the most [114:33] important part and part of the reason we [114:36] lose our vision is the mitochondria [114:37] don't make enough energy for the eye [114:39] >> how come you haven't done red light [114:40] therapy before then [114:42] >> well I do but not uh routinely so I have [114:46] one of those bricks that I turn on while [114:48] I'm in the shower [114:49] >> and I have a red light cap for my hair [114:50] which there's some evidence. [laughter] [114:52] >> My wife has one of those. [114:53] >> It works. [114:54] >> Looks like a [ __ ] alien. [114:55] >> What I do is I Yeah, it does. It looks a [114:58] little bit silly. [114:58] >> I don't wear it in public, but um I do [115:00] lower it and I look at it and it shines [115:03] in my eyes and on my face [115:04] >> in the hopes that it might help be help. [115:06] >> Yeah, they have one that you wear like [115:07] Dr. Doom like fits over your face and [115:09] like blast red light in your whole face. [115:11] >> I definitely feel a bit weird afterwards [115:14] and I can see speckles, but I I think [115:16] the science says that it can help. Well, [115:19] all I know is my own anecdotal [115:21] experience and for me it has radically [115:25] improved my vision. [115:26] >> That's a good tip. [115:27] >> Yeah, it stopped. Well, it was my vision [115:30] was degrading like it was it was pretty [115:33] o like I first started using like [115:36] reading glasses like a onex like it made [115:38] it a little better. I'm like, "Oh, this [115:39] a little better. Makes it clearer." And [115:40] then I went to two and then I was using [115:42] 2.5, right? [115:44] >> And it made it better, but it was like, [115:46] "God, this is annoying." And then if I [115:48] would try to like read an email and it I [115:51] didn't have my reading glasses, I [115:53] couldn't read [ __ ] Now crystal clear. [115:55] >> Yeah. [115:56] >> No problem at all. [115:57] >> Well, uh so my my latest show is about [115:59] the eye and how to protect the eyes's [116:00] health and so there's a lot you can do [116:04] actually supplements um red light other [116:06] things. So [116:07] >> I take supplements for it too. I should [116:09] mention that I take um no I have no [116:11] affiliation with these people but Pure [116:13] Encapsulations makes a uh a supplement [116:16] called macular support and I take that [116:18] and it's a combination of luteine and a [116:20] few other things. [116:21] >> Yeah, there was a a trial uh a while ago [116:25] that showed that taking zanthine and [116:28] others aanthine lute luteine they're [116:31] good for uh the eye. So you can get [116:33] products like that. [116:34] >> Do you take it? [116:35] >> Not that brand but yes I take something [116:37] similar. And has it helped you at all? [116:40] >> I don't know. I haven't done an [116:41] experiment. [116:42] >> Right. Well, if you weren't taking it, [116:43] maybe you would have more degeneration. [116:45] >> Yeah. Well, you know, I've got near [116:48] perfect vision. I don't need glasses. [116:49] >> Do you really? [116:50] >> Oh, yeah. [116:51] >> Near perfect. [116:51] >> Near perfect. I mean, I think low light [116:54] >> low light is with me. Yeah. Where I'll [116:56] go to a restaurant with my kids and they [116:58] can read the menu and I'm like, that is [116:59] so embarrassing. You can read that? How [117:02] do you even read that? I can't read [117:04] [ __ ] Like, do you know why? [117:05] >> Why? Well, this is this is what I think. [117:08] So, we know from my lab's work that the [117:10] retina because it has tens of thousands [117:13] of endings that that pick up the light. [117:16] As you get older, those nerves lose [117:18] their identity and they're not working [117:20] as well. And what we do is with our [117:23] therapy, we can restore those nerves [117:26] back to being functional nerves. And [117:29] that's why mice and monkeys that lose [117:32] their retinal function get their perfect [117:35] vision back again. [117:37] >> We're reminding those cells that have [117:39] forgotten how to work. So in your eye [117:40] and my eye were 22 months apart that [117:43] those nerves about half of them have [117:45] forgotten how to work properly. So we [117:47] want to fix that and go back to being [117:49] young. It's not that our nerves are [117:50] gone. They're not dead. They're right [117:52] there and we can restore them. [117:53] >> And that's going to be true for a lot of [117:55] organs is that the cells are still [117:56] there. They just need to be reminded how [117:58] to work again. [117:59] >> What are the potential negative [118:01] consequences of this kind of work? Like [118:04] when you when you sit up at night and [118:05] you worry, I hope it doesn't do this. Is [118:09] it cancer? Is that the big one? [118:10] >> Yeah, it's though we've done a lot of [118:13] work to allay real fears. It is possible [118:17] that if we go too young, we can cause [118:19] displasia, which is cells doing what [118:21] they shouldn't, or if they multiply and [118:23] spread. That would be careful. You make [118:25] the cells too young. Like what I was [118:26] saying before about don't turn me into a [118:28] baby, [118:28] >> right? We don't want to go there. That's [118:30] what Yamanaka did and got the Nobel for [118:32] it. But that's not good here. But we we [118:35] never see ourselves turn into stem cells [118:37] again. We can't we we had mice that we [118:40] left it left the gene therapy on for 21 [118:43] months in the eye and 19 months in the [118:45] whole body of the animal. And if [118:47] anything, they had less tumors than the [118:49] ones that didn't get treated. M [118:51] >> and we actually know from a wonderful [118:53] student in my lab, Natal, uh she's a PhD [118:56] student. She found that when you turn on [118:58] these three same genes, not in the eye, [119:00] but in cancer cells and tumors growing [119:03] in mice, human cancers growing in mice, [119:05] they shrink. So, we think it might [119:07] actually help for cancer as well, which [119:08] was a nice surprise. [119:10] >> Wow, that's incredible. [119:12] >> It makes sense, right? If you wake up a [119:13] cancer cell and it says, [119:16] >> "Crap, I shouldn't be growing. I should [119:18] be a you know a liver cell or or [119:22] something similar. Uh now it kills [119:24] itself. So we see that the cells wake up [119:26] they realize what they were 30 years ago [119:29] and then they kill themselves. [119:32] >> What what is on the horizon in terms of [119:34] like what would you like to accomplish [119:36] or would you like to work on that you [119:38] can't do currently? [119:40] >> Well, lots lots you know funding in my [119:43] lab got completely cut last year. Uh and [119:46] we've managed to survive through [119:48] donations. We uh [119:50] >> Why' the funding get cut? Was it a US [119:51] aid thing? [119:52] >> You remember uh there was a spat between [119:54] Harvard and the federal government. All [119:56] of the funding to Harvard Medical School [119:58] got cut. [119:58] >> Was that during the time where the [120:00] president was defending those [120:03] anti-semitic comments on campuses? [120:07] >> Yeah. Uh well, allegedly, I'm not [120:09] getting into the politics. [120:10] >> No need to get into politics, but during [120:12] that whole thing. Yeah. [120:14] >> Yeah. So what what we we I almost had to [120:16] fire most of the people in my lab during [120:18] that episode. It was quite scary, but I [120:21] god [120:22] >> raised don. So now my lab survives on [120:24] donations. Uh not on federal government [120:26] money. Thank you friends. Thank you. [120:29] Thank you. [120:30] >> Well, the thing is you've accomplished [120:32] enough where people are like, I think [120:34] he's on to something and I want to live [120:36] forever. [120:36] >> Well, I'm lucky. Most scientists can't [120:38] raise money like that. So really, really [120:40] it's a blessing. And now I'm raising [120:41] money through a foundation to help other [120:43] scientists survive. But yeah, it's it's [120:46] been a blessing. But your question um [120:49] was what do I wish I could do? [120:51] >> Yeah, [120:51] >> I wish I could go faster. I wish I could [120:53] try multiple approaches so we don't just [120:56] have one shot on goal. [120:57] >> Um it's going slower than I would want [121:00] with a big injection of cash. We could [121:02] do a lot of trials, a lot of different [121:03] tissues. We could do a whole body re uh [121:07] rejuvenation as well. Do you have a [121:08] website where people can donate? [121:11] >> Um, I do. It's lifespan.com. [121:14] >> So, if you go to lifespan.com, [121:17] >> there's a link there you can donate. [121:19] >> Foundation. And we're raising money for [121:21] this type of research. [121:22] >> Is it taxdeductible? [121:24] >> Uh, depends on how big the donation is. [121:26] Uh, for $10, you get the new magazine [121:29] that we're putting out and you learn all [121:31] about uh how to live longer building. [121:33] I'm hoping to build the world's largest [121:35] longevity community of millions of [121:36] people who can learn how to really live [121:39] longer and build healthcare from the [121:40] ground up because top down from the [121:42] government hasn't worked. [121:43] >> Yeah. Actually, I have I have a gift for [121:45] you. [121:46] >> Where you at? [121:47] >> I made something for you that's unique. [121:49] >> Oh, I brought it here. [121:52] >> This is for you, Joe. As a thanks to all [121:55] the support you've given me and the [121:57] science over the years. [121:58] >> First edition [122:00] lifespan magazine, ladies and gentlemen. [122:02] Look at that. [122:03] >> It's written by scientists [122:05] >> cover. It's like a velvet cover. What is [122:07] this? [122:08] >> I figured you might like that. Inside is [122:09] the magazine. And [122:10] >> what is this material? It's beautiful. [122:12] >> Velour. [122:13] >> Velour. Oh, velour. Of course. [122:15] >> At great expense. No, the magazine [122:17] doesn't come with velour. That's just [122:18] special for Joe [122:19] >> as a thank you present. [122:21] >> Thank you very much. [122:22] >> Most most science out there is written [122:24] by reporters who don't know what they're [122:26] talking about. And uh so we want we [122:29] wrote this for the public and you can [122:31] believe whatever you read in there. [122:32] >> All right. Beautiful. And the lure so [122:35] you have to trust it. [122:36] >> So that's at lifespan.com. You can [122:38] subscribe. Get that every month just for [122:40] 10 bucks. [122:41] >> I like the take at the bottom. Life's [122:43] too short. Let's fix that. [122:45] >> That's our slogan at lifespan. [122:47] >> Slogan. [122:48] >> Yeah, [122:48] >> that's an awesome slogan. [122:49] >> Uh so it's it's a it's a community. It's [122:52] the show. My show is also called [122:54] Lifespan on YouTube. But the magazine is [122:56] a passion project. I want to put out [122:58] something that people love. It's [123:00] beautiful, right? It's like National [123:02] Geographic. By the way, the just today, [123:05] this is no, no joke. It seems crazy, but [123:09] my lab's research is on the cover of [123:11] National Geographic. [123:12] >> Oh, that's awesome. [123:13] >> That just came out today. They they [123:15] heard, by the way, at Nat Geo, they [123:16] said, [123:17] >> "You going on Joe Rogan?" I went, [123:18] "Yeah." They goes, "Right, we'll put it [123:20] out early." So, you can now read about [123:22] my lab's research on Natio as well [123:24] today. [123:24] >> That's very cool. That's very cool. So, [123:27] you would just like to do more have more [123:30] funding, do more that that's the thing [123:32] that you wish you could be working on [123:34] now, just having more different more [123:36] different studies and tests running [123:39] concurrently. [123:39] >> We could go so fast with AI because it's [123:41] spitting out new drug candidates all the [123:43] time that we can't test. It takes years [123:45] to get through. So, with money, we could [123:47] do a lot more trials and put these [123:49] through different diseases much faster. [123:52] >> If you had no regulations, like an [123:53] island of Dr. Maro type deal. [123:55] >> Yeah. [123:55] >> Will you let you know? [123:57] >> Well, at the risk of getting kicked out [123:58] of my university, um theoretically we [124:03] could very safely do more animal studies [124:07] and with those best candidates put them [124:09] into humans quicker. [124:11] >> Right now, it takes years. It's taken us [124:13] close to 10 years to go from the first [124:15] discovery in my lab in Nature magazine [124:18] to now. But that's too slow. People [124:21] dying 150,000 a day on this planet. It's [124:24] terrible. So, I would love to have the [124:26] resources, you know, like Jeff Bezos and [124:29] others. [124:30] >> Yeah. [124:30] >> My my company, by the way, even though [124:31] we lead the pack of all these guys, um [124:34] we're really small. We're we're a pretty [124:36] small little outfit in uh in Boston. Uh [124:40] we've raised a lot less money, but we're [124:42] because I think we're focused. We have [124:44] and we started earlier. We're doing [124:45] pretty well. [124:46] >> That's the big one. You started earlier. [124:48] You have a lot of momentum on your side. [124:50] >> Yeah. But we I think we we we could have [124:53] a big impact on aging in our lifetime [124:55] with more money directed in general at [124:58] the field, not just me, but spread it. [125:01] And so the money that we raise from the [125:03] magazine is going to support other labs [125:06] as well um and students who can find [125:09] these medicines quicker. So if you in a [125:12] perfect world and you had unlimited [125:14] resources, you would just run a bunch of [125:17] different clinical trials and studies [125:20] concurrently and [125:21] >> yeah, AI is feeding us molecules. We put [125:23] them into mice, we go to monkeys, we go [125:24] to humans, and it would just be fast. [125:26] one of my friends um Alex Zakaronov uh [125:29] he has a similar uh company but not on [125:33] exactly what we do not on reprogramming [125:35] but he's able I think he's on his 35th [125:38] drug but he's driven by AI and robots [125:43] his whole lab is robots uh at least he [125:45] says they are and then uh goes into [125:48] humans and his company is worth billions [125:50] um that approach applied to what we do [125:53] would be incredible M that's best case [125:57] scenario. That would be incredible. [125:59] Well, I'm hoping through this [126:01] conversation that people are going to [126:03] reach out and I'm hoping through this [126:04] conversation that people realizing like, [126:06] oh well, so much work has been done and [126:09] so many breakthroughs have been made if [126:12] they had more access to resources, more [126:14] access to different whatever you need, [126:18] you know, and that you could run all [126:19] these different studies. [126:21] We we could we we're our budget in my [126:24] lab is only it's almost three three and [126:27] a bit million. It's not much, right? [126:28] Compared to what impact it could have on [126:30] the planet, which is trillions of [126:31] dollars saved just in the US alone. So, [126:34] it's it's a little bit of donation or or [126:38] getting a magazine, the impact would be [126:40] life-changing for all of us. [126:43] >> Who doesn't age? Who doesn't get [126:44] diseases, [126:45] >> right? And who doesn't want to feel [126:46] better? [126:47] >> Yeah. It's also like so much you can get [126:50] so much more done if you feel better. [126:53] >> Well, we we take it for granted until we [126:55] feel sick and it's like a I forgot what [126:57] it's like to feel well. [126:58] >> Exactly. Exactly. I had a day a week and [127:02] a half ago where uh I came back from [127:05] Italy. I was a little jet-lagged. I [127:07] could didn't sleep right and I worked [127:09] out really hard a bunch of days in a row [127:11] and I was working constantly and then I [127:13] had one day I was like I kind of feel [127:15] like [ __ ] like I better not do anything [127:18] today. [127:19] >> And I, you know, after I was done work, [127:22] I just watched TV and relaxed. I [127:25] >> went and I was like, I can't wait to [127:27] feel better again. [127:28] >> Well, imagine what it's like being old. [127:30] >> Yes. [127:30] >> And frail. That's every day. [127:32] >> Yes. Or sick. [127:33] >> And right now, you can't do anything [127:34] about it. [127:35] >> Yes. Yeah. And while you're healthy, you [127:39] take it for granted. And that's the real [127:41] sin. Like you're like, "Ah, I'm fine. [127:44] I'm great." I mean, this is what people [127:45] do when they go out drinking, right? [127:47] They they take advantage of the fact [127:49] that uh it's worth it for a good time. [127:51] Just poison myself for a night. [127:53] >> Well, it's not worth it because that [127:55] also accelerates aging [127:56] >> big time, right? [127:57] >> Says what I tell my kids who like [127:59] alcohol like most kids. You know, you [128:02] might feel better in a in a few days, [128:03] but the memory of that is going to be in [128:06] your body. [128:06] >> Yeah. [128:07] >> Think you can drink. It's, you know, [128:08] it's fine to get drunk once in a while. [128:10] Uh but not a lot. Not constantly. I used [128:12] to drink once a day and I do not do that [128:15] anymore cuz the the data is [128:16] incontrovertible that it affects the [128:18] brain, even the size of the brain if you [128:20] drink constantly consistently. [128:22] >> I took eight months off of no alcohol at [128:23] all and I felt a lot better. [128:25] >> Exactly. [128:26] >> I started drinking again one night. I [128:28] went to dinner with my wife and had a [128:29] margarita. I was like, "Oo, I think I'm [128:31] back." [128:32] >> Oh, really? Well, I [128:34] >> So, I drink now. I do not get drunk. I [128:37] haven't gotten drunk. This was over a [128:38] year ago was when I had a drink again, I [128:41] think. I think it was a year. I'm not [128:42] sure. But point is uh I have not been [128:45] drunk since then. [128:46] >> Yeah, [128:47] >> I will have a glass of wine with dinner [128:49] or I will have uh a like a shot of [128:52] whiskey before I go on stage like a [128:54] little bit, but I do not get drunk [128:56] anymore. [128:57] >> It's just not worth it to me. The [128:59] feeling afterwards is so terrible the [129:02] morning. And especially for me because I [129:04] work out so much. When I wake up, it's [129:06] like that workout's going to get done. [129:08] Okay? Whether I feel like [ __ ] or not, [129:09] that workout's going to get done. and [129:11] this is going to be rough. [129:12] >> And you got the sweats. It's hard, [129:13] >> right? Versus when I feel great, I love [129:16] the workout. I'm excited. Like, I look [129:19] forward to it. Even when it's hard, when [129:21] it's over, I'm like, "All right, let's [129:23] eat." And I don't feel bad. I feel good. [129:26] And it's like, why am I giving up that [129:29] for A FEW HOURS OF, [screaming] [129:32] YOU KNOW, it's just not worth it. It's [129:34] not worth it. [129:34] >> Yeah. Well, you're funny even without [129:36] alcohol, but I'm I'm not. So, I've lost [129:38] a lot of my humor. [laughter] [129:39] But the the there's nothing better than [129:42] feeling great, right? And if you can [129:43] make it your hobby [129:45] >> of working on your health and your [129:47] longevity, [129:48] >> you'll enjoy it. [129:49] >> Yes. [129:50] >> It shouldn't be a chore. [129:51] >> It'll also directly affect the other [129:54] things that you love cuz you will have [129:56] more energy. Your life energy, your [129:58] vitality is so important for anything [130:01] you're doing. Whether it's a creative [130:03] thing or an intellectual thing, like [130:05] anything that you're doing, if you have [130:07] more energy, you'll be able to apply [130:09] more energy to that thing. It's that [130:11] simple. You're building a bigger gas [130:13] tank for yourself. You're building a [130:15] larger engine. And that's what you're [130:17] doing. [130:17] >> Exactly. Mentally, physically, you can [130:20] do so much when you feel good. You jump [130:21] out of bed. If if you wake up and you're [130:23] tired, woozy, you know, your eyes are [130:26] puffy, that's not how it should be when [130:28] you wake up. If you're getting and sleep [130:30] is important for longevity, of course. [130:31] If you're getting good deep sleep, then [130:33] you should wake up and you feel great. [130:35] >> Yes. [130:36] >> You don't even necessarily need a cup of [130:38] coffee, but it's not bad if you have [130:40] one. [130:40] >> I like coffee. I'm not going to stop [130:42] drinking it. [130:43] >> No, man. [130:43] >> I don't give a [ __ ] what anybody says, [130:44] >> right? It's good. And [130:45] >> there's also like conflicting [130:47] information. Some people say it's good [130:49] for you. There's benefits. [130:50] >> It's good for you. Come on. [130:52] >> That's what I say. [130:52] >> Oh, it really is. Anyone that says it's [130:54] not doesn't read the list. [130:55] >> Well, I would imagine an overabundance [130:58] of caffeine is not good. Too much is not [131:02] good. But that's what [131:03] >> true for everything. [131:03] >> Too much salt will kill you. You know, [131:05] you pound of salt, you'll be dead in an [131:07] hour, [131:07] >> right? You can get away with very little [131:09] sleep actually as long as it's deep [131:10] sleep because what it's doing is [131:12] clearing out the misfolded proteins in [131:14] your brain and the toxins. We know this, [131:16] the glimpmphatic system. And if you get [131:19] deep sleep for, you know, an hour, [131:21] you're actually going to wake up much [131:25] cleaner, healthier. And what I've been [131:27] able to do with some work is figure out [131:30] how to get deep sleep every night, [131:33] efficiency on these rings that say above [131:35] 90 sometimes. [131:36] >> I like you say rings, cuz you're wearing [131:37] two aura rings. [131:39] >> Uh, [131:40] >> or one aura. Okay. Why do you wear two [131:43] different rings? Um [131:48] because when I've got two, neither of [131:49] them is correct. No, the [laughter] [131:53] the truth is some of them uh some of [131:55] them are really good for sleep, the [131:56] others are good for heart. And so I've [131:59] this one's my heart and this is my [132:00] sleep. [132:01] >> What is the difference in the companies? [132:03] Which one's which? [132:04] >> Um uh you don't mind me saying who they [132:06] are? [132:07] >> No, I don't care. [132:07] >> Uh this is an Aura, the fat one, and [132:09] then the thinner one is called Ultra [132:11] Human. [132:11] >> Ultra Human? [132:12] >> Yeah. [132:13] >> And which one is good for what? Well, I [132:15] find Aura really good for sleep. That's [132:16] their specialty. Um, and then the heart [132:19] for ultra human, my cardiac age. [132:22] >> Oh, okay. So, it's just like giving you [132:24] data all the time. [132:26] >> Yeah. And they're getting even better [132:27] cuz they I don't get paid by these [132:29] companies, but I do like that they pop [132:31] up with AI information now. [132:33] >> Mhm. [132:34] >> Have you noticed that da da or I noticed [132:36] that you ate a meal last night that [132:38] spiked your glucose? You know, and this [132:41] one I have a monitor on right now so I [132:43] can see what's going on. Anyway, but [132:44] yeah, they're they're becoming like [132:46] >> You are [ __ ] monitored, bro. [132:48] >> I am. [132:48] >> Two rings and a patch. [132:50] >> It's a It's a hobby. It's a hobby. But [132:52] you learn a lot. And I put one of these [132:54] on my son and he stopped eating bad food [132:57] for for a long while. [132:58] >> Really? Cuz he was just recognizing the [133:00] impact that it had on his body. [133:01] >> It's good for kids. Now, I wouldn't say [133:03] slap it on a kid without pediatrician uh [133:06] recommendation, but it was amazing what [133:09] happened when he could see the crap that [133:11] was going in his mouth was doing to his [133:13] blood sugar. [133:14] >> Really, [133:14] >> it was amazing. I I think it's a great [133:16] learning tool if nothing else, [133:18] >> right? Just to have actual data. I know [133:20] a lot of people it's changed their [133:22] opinion on alcohol particularly the aura [133:24] ring when they look at their sleep [133:26] >> because even just a couple of drinks [133:28] before you go to bed like a couple of [133:30] drinks at dinner and then you realize [133:32] like oh god my sleep was all [ __ ] up [133:35] because of those drinks. [133:37] >> Yeah. Lay off the medapanyl too for me [133:39] anyway. [133:41] >> Yeah. Some medafyl [ __ ] with your sleep [133:42] as well. [133:43] >> Yeah. Yeah. [133:44] >> I have to work really hard to sleep [133:46] well. There's there's quiet time. [133:48] There's relaxation. the lights are [133:50] dimmed. Um, I think about a happy place [133:53] rather than work. I had to do that [133:55] because for 50 years I was burning the [133:56] candle at all ends. I was really burnt [133:59] out and so I've fixed that now. I don't [134:01] worry. [134:02] >> So, are you one of those guys that like [134:03] dims the lights in your house a couple [134:05] hours before you go to bed, prepare, [134:08] stay off your phone, [134:09] >> all that stuff. [134:10] >> Well, I don't stay off my phone as much [134:12] as I want to, but um yes. [134:14] >> You wear red light glasses or anything [134:16] like blockers? [134:16] >> I used to. I haven't found a big [134:18] difference. [134:19] for myself. But um interesting fact that [134:22] isn't well known. If you block blue [134:24] light during the day or just stay [134:25] indoors, there's a guy in Japan uh who [134:28] says that what what happens is you get [134:31] shortsidedness. [134:34] >> And really cuz the mice that lack the [134:37] ability to sense violet light get [134:39] myopia, short-sighted. And he's got a [134:42] device that indoors you can shine this. [134:43] that our modern world, the LEDs and [134:47] being indoors means we barely get violet [134:49] light. And that would been that would be [134:50] so interesting if that's what's causing [134:52] us to have have to wear glasses. [134:54] >> Wow. [134:55] >> And he claims that people that live out [134:57] in the countryside that see blue light [134:58] all the time cuz they go out don't have [135:00] as much need for glasses. [135:02] >> That actually makes sense. Well, [135:04] particularly like artificial light and [135:06] then also light that's from a close [135:09] source. Like one of the things that uh [135:11] if I do if I'm if I'm tired and I lay in [135:14] bed and I try to read something online [135:16] on my phone, it hurts my eyes. The [135:19] room's dark and it's like it irritates [135:21] my eyes where it never irritates my eyes [135:23] normally, but it's like at the end of [135:25] the day, you know, I guess I'm more [135:27] fatigued and so then [135:29] >> and you're trying to focus on screen. [135:30] >> So like now think about that when people [135:33] are doing it all day long. Maybe you're [135:34] doing it at work where you have to stand [135:35] stare at a computer monitor from 3 ft [135:37] away or or closer and then you're [135:39] looking at your phone all the time or [135:41] you're working from a tablet or you're [135:43] watching television. It's like you're [135:44] constantly staring at these light [135:46] sources that are artificial. [135:48] >> Yeah. And also keep in mind that the [135:50] muscles have to focus. It's not natur [135:52] you don't naturally look this far. You [135:54] naturally you relax you see out there. [135:56] But [135:56] >> to look here, your muscles here have to [135:58] be straining for hours and they get very [136:01] tired. [136:02] >> And I guess eventually they age to a [136:04] point where you cannot keep it up. [136:06] >> And sometimes I do this to see better [136:08] though. [laughter] [136:10] >> Well, it it it all makes sense if you [136:12] think about it. Particularly like if [136:14] your eyes are accustomed to only [136:16] focusing on things that are close. I [136:17] mean, that was what they would say about [136:19] reading when people would have glasses. [136:20] Oh, you [ __ ] up your vision reading, [136:22] which [136:23] >> I used to think was nonsense, but I'm [136:25] like, well, kind of makes sense if you [136:27] spend all day long focus even even [136:29] though it's on a screen. You're spending [136:30] all day long focusing on a book that's [136:32] only a foot from your face. Yeah, [136:34] >> it does make sense. [136:34] >> And the lens gets really inflexible, [136:37] >> right? [136:37] >> And I'm seeing this with my father. He's [136:39] otherwise in perfect health at 87, which [136:41] is amazing. But it's his eyes that are [136:43] failing him. [136:44] >> Maybe you should get him a red light [136:45] bed. [136:46] >> That's a great idea. Yeah, [136:48] >> I'm going to do that. He's arriving [136:49] tonight actually from Sydney. He's uh [136:53] >> Get him a red light bet, man. Because [136:54] I'm telling you, there's not a thing [136:56] that I've done that's impacted me in a [136:58] more obvious way than that in terms of [137:01] like something that's hugely important. [137:03] >> I'm going to do it. And uh I mean he's [137:05] into science. He's been taking Naman, [137:07] resveratrol, metformin, exercising, [137:10] going he goes to the gym two or three [137:11] times a week, walks six months. [137:13] >> Great. I He's a role model at 87 with no [137:16] diseases, no aches or pains. [137:19] >> He's traveling the world. He was in [137:20] Japan two weeks ago. [137:21] >> Wow. [137:21] >> Coming to Coming to Boston. [137:23] >> That's That's so cool. I love hearing [137:26] about people that are older that just [137:28] keep on top of it and stay active and [137:29] stay alive and enjoy life. [137:31] >> Yeah, exactly. He's a great role model [137:33] and it what it shows is he was an [137:35] average guy till he was in his 60s and [137:37] he figured I was he was going to die in [137:39] his 70s probably cuz everyone in my [137:41] family dies young cuz we've got pretty [137:42] bad genes but he's just taken life by [137:45] the horns and just is running with it [137:47] and has not physically aged except for [137:50] his eyes in the last 20 years. [137:53] >> That's incredible. [137:54] >> And that's not an exaggeration. Anyone [137:55] who's seen him [137:56] >> uh knows he walks, he moves, he travels, [137:58] he does everything like he was when he [138:01] was 40. That's where where things like [138:03] resistance exercises are so important [138:05] because it maintains bone density, [138:07] maintains muscle mass, maintains your [138:09] ability to just get around and do [138:10] things. [138:11] >> That's the other reason to to do that. I [138:14] mean, you're you're going to be really [138:15] strong when you're older and you won't [138:16] fall. And if you do fall, you'll bounce. [138:18] You won't break a bone. And he he's like [138:20] that. He's been working out at the gym, [138:22] mostly strength training, but balance as [138:24] well. It's very important to maintain [138:25] balance. He's better at the gym than me [138:28] at 87. [138:29] >> That's incredible. That just shows how [138:30] weak I am. [laughter] [138:33] >> Yeah, I got to go to the gym. How about [138:35] next time if you have me on, [138:37] >> you're going to be buff. [138:39] >> We'll get you a trainer. You're in [138:40] Massachusetts. [clears throat] There's a [138:41] ton of trainers out there. [138:42] >> Great. [138:44] >> It's a deal. [138:45] >> We'll find you someone. We'll find you [138:46] someone. Three days a week. That's all [138:48] you need. The other days you could do [138:50] stuff [138:51] elective, do stuff that you want, you [138:53] know, but three days a week, get a a [138:55] personal trainer and have work out with [138:57] them. [138:57] >> Right. You're you're on. All right. [138:59] >> I will let you know when it's going or [139:01] you help me. I can hear though that [139:03] there's probably a few million people [139:05] right now screaming, "David, just go go [139:06] to the lab. Forget about the gym. You [139:08] need to make [139:09] >> Well, it'll help your lab work. It'll [139:10] help everything. It'll help the amount [139:12] of research you're able to do. You'll [139:13] have more energy. You'll be more excited [139:15] about things." I'm sure you've seen [139:17] those MRI cross-sections of people's [139:19] tissue where they uh take like a [139:21] 70-year-old man who's sedentary versus [139:24] 70-year-old man who's a marathon runner. [139:26] It's [ __ ] extraordinary. [139:28] >> I've seen my own. Uh there's there's too [139:30] much fat in the muscle. Got to get rid [139:32] of it. [139:32] >> Yeah. Yeah. It's really extraordinary [139:35] when you see those images like those [139:36] really bring it home. [139:37] >> And the bone changes. Bone turns to fat [139:39] too. [139:40] >> Uh parts of the bone. So you got you got [139:42] to have the strength training for sure. [139:44] Keep [139:45] >> bone strong. [139:46] >> Yeah. 100%. Strength training is it [139:49] that's mandatory. [139:51] >> Yeah. And then the Do you do a lot of [139:52] aerobic exercises? [139:53] >> Yes. [139:54] >> Good. Yeah, [139:54] >> I saw the training bike. [139:56] >> Oh, yeah. Well, you saw my hypoxia [139:58] machine that I just got installed today. [140:01] >> Yeah. Um the the the hypoxia thing, what [140:05] it does is it um replicates 14,000 ft [140:09] above sea level [140:10] >> and you train in it. And it also has a [140:13] heat element, so you could ramp the heat [140:14] up to 115°. So 115° and and 14,000 ft [140:20] above. [140:20] >> Much pitch kind of stuff. [140:22] >> Yeah. You're going to hell. That's what [140:23] it is. you go straight straight to hell. [140:25] >> Feel like it, [140:26] >> but it should work, right? Epoxy is [140:28] great for muscle. [140:29] >> Yes. And for adaptation. That's the the [140:31] big thing. And uh my friend Roman who [140:33] installed it, who's owns one of the guys [140:35] from the company, um they it's a very [140:38] they're very specific with this protocol [140:41] with in terms of monitoring your heart [140:42] rate, when to do it, when to push, how [140:44] much time to spend, and how you do it. [140:47] And it's very scientific in terms of the [140:49] application on athletes. [140:50] >> Yeah. And it has a my friend Adam [140:52] Greenree turned me on to it. [140:54] >> Okay. [140:54] >> Uh fellow Australian um and uh he uh [140:59] he's a a big hunter and does a lot of [141:01] mountain hunting and he said there's [141:03] nothing he's ever done that's had more [141:04] of an impact on his cardio. So it's been [141:06] phenomenal. Sounds wonderful actually. [141:09] Um there's a lot of science behind that. [141:11] Um you probably know it. The best [141:14] results are when people are either [141:17] having too much oxygen or not enough. [141:20] Mh. [141:20] >> And you might say, "Well, that's weird. [141:22] Why does it matter?" Well, you you got [141:24] to get out of your com comfort zone, [141:25] hormesis, we keep talking about, [141:27] >> and there's a a big study in Israel [141:31] where they put people in these [141:32] hyperbaric chambers. [141:33] >> I've done that protocol. [141:34] >> Yeah. [141:34] >> Yeah. 60 sessions of 90 minutes over uh [141:38] 90 days. [141:38] >> Yeah. [141:39] >> Yeah. [141:40] >> Yeah. [141:40] >> I have one in my house. [141:41] >> You do? [141:41] >> Yeah. [141:42] >> Because the the data is [141:43] incontrovertible. Better wound healing, [141:45] better memory, [141:46] >> increase in telmir length. [141:47] >> Yeah. I saw that one. That that's the [141:49] Israel study. [141:50] >> Yes. [141:51] >> What I thought was interesting was when [141:52] I I went over there myself and sat in [141:54] that thing. [141:55] >> Um they made a joke over there in [141:57] Israel, by the way. They said this gas [141:59] chamber here that you going into made by [142:02] Germans. I thought that's not a funny [142:03] joke. Don't say that again. [laughter] [142:05] Anyway, uh I probably shouldn't have [142:07] shared that. I I did go into the chamber [142:10] and uh what I what I found out and was [142:13] that they believe what I believe which [142:14] is it's not so much the high pressure [142:17] that's good for you, it's the coming [142:19] down that mimics hypoxia which your room [142:21] will mimic. [142:22] >> So the lack of oxygen or the perceived [142:24] lack of oxygen from a high state is the [142:26] benefit. [142:27] >> Interesting. [142:28] >> And that makes a lot of sense. You're [142:29] going to grow new blood vessels just [142:30] like Viagra uh is going to open things [142:33] up. We actually had a paper uh 2012 [142:37] that found that one of the supplements [142:39] that I take, which everyone knows about, [142:41] NMN, could allow animals to grow new [142:44] blood vessels by getting rid of a [142:48] protein that accumulates with aging. The [142:50] bottom line is we could mimic uh this [142:54] lack of blood vessels with this pill, [142:56] but by exercising it's it's the same. [142:59] What I really believe which is is barely [143:03] talked about in the medical [143:04] establishment is that a major reason we [143:06] get sick when we get older is lack of [143:08] blood flow. It's rarely talked about, [143:10] right? Vascular dementia, second largest [143:13] cause of dementia in the world. Blood [143:16] flow. And it's the easiest to reverse. [143:19] You just do exercise or take [143:21] >> one of these PD5 inhibitors, Viagra. Um [143:25] or you take my stuff which is anaman [143:27] which we think also works [143:28] >> or all the above which is probably the [143:30] best approach. [143:31] >> Uh I'm two out of three [laughter] [143:34] hopefully soon three out of three but [143:36] yeah you know to protect your brain [143:38] which is the most important because you [143:40] don't want to be old and demented. [143:41] That's that's worse than anything. [143:43] >> Keep the blood flowing in your body. [143:45] Remember that blood flowing is [143:46] important. [143:47] >> Yes. Couldn't agree more. David, you're [143:50] a treasure. I really appreciate you. [143:52] Thanks for being here. you've been so [143:54] kind and thank you for getting the word [143:55] out here about the great science that's [143:57] going on. [143:57] >> Oh, my pleasure, dude. I'm so happy [143:59] there's someone like you out there doing [144:01] this. I mean, it's it's such an enormous [144:04] benefit to people that are listening to [144:06] the world and you're doing you're [144:08] literally doing God's work [144:09] >> and we'll we'll try to do more. [144:11] >> Thank you very much. Um lifespan.com [144:14] is the website. Please, folks, if you [144:17] you're so inclined, go donate. It'll [144:19] really help. It'll change the world. [144:21] >> David, you love you [music] too. Thank [144:22] you. Bye everybody. [144:29] [music]