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Dr. David Sinclair: The Biology of Slowing & Reversing Aging | Huberman Lab Podcast #52

Andrew Huberman・113 minutes read

Dr. David Sinclair discusses aging as a disease that can be slowed or reversed through interventions like diet, supplements, and behavioral changes, emphasizing public education on aging biology and practical tools. The 'lifespan podcast' launching on January 5th, 2022, aims to educate on aging biology, reversing aging, and providing actionable protocols for increasing lifespan, featuring discussions with Dr. Sinclair.

Insights

  • Dr. David Sinclair, a genetics professor at Harvard Medical School, views aging as a disease that can be slowed or halted through intervention points identified in behavioral, nutritional, supplementation, and prescription drug methods.
  • Aging is equated to the loss of information due to entropy, with genetic and epigenetic information playing crucial roles in longevity and health, emphasizing the importance of controlling gene expression for combating aging effects.
  • Intermittent fasting, supplements like NMN and resveratrol, and exercise play pivotal roles in activating defense mechanisms for longevity, with personalized adjustments necessary based on individual responses and factors like microbiome composition and age.
  • The potential for gene therapy to rejuvenate the body, starting with eye treatments to reverse age-related damage and blindness, showcases groundbreaking advancements in science that may have far-reaching implications for human health and longevity.
  • Public health education efforts, advancements in biological age testing, and the democratization of health information aim to empower individuals to make informed decisions about their well-being, bridging the gap in understanding and offering personalized recommendations for improving overall health and lifespan.

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Recent questions

  • How can aging be viewed according to Dr. Sinclair?

    Dr. Sinclair views aging as a disease that can be slowed or halted, contrary to it being a natural consequence. He believes that aging can be combated through various methods such as behavioral changes, nutritional adjustments, supplementation, and prescription drugs. By identifying intervention points and addressing the underlying causes of aging, Dr. Sinclair aims to educate the public on aging biology and interventions to promote longevity and overall health.

  • What is the focus of Dr. Sinclair's 'lifespan podcast'?

    The 'lifespan podcast' launched by Dr. Sinclair on January 5th, 2022, focuses on aging biology and intervention tools. The podcast aims to educate listeners on the mechanistic science behind aging, ways to reverse aging, and practical tools for daily life. Dr. Sinclair, along with his guests, discusses aging, longevity, and actionable protocols to increase lifespan, emphasizing aging as a disease that can be addressed by understanding its underlying mechanisms.

  • How can intermittent fasting impact longevity?

    Intermittent fasting, particularly skipping a meal a day or longer fasting periods like 48 or 72 hours, can trigger autophagy, a process that cleanses the body of old and misfolded proteins. By activating sirtuins and down-regulating mTOR through fasting, the body's defense mechanisms for longevity can be triggered. Research suggests that periods of hunger, rather than actual hunger, activate defensive genes for longevity, making intermittent fasting a potential tool for promoting health and extending lifespan.

  • What are the benefits of NMN supplementation?

    NMN supplementation impacts the sirtuin pathway and aging rates, serving as a precursor to NAD crucial for sirtuin activation and cellular functions. By taking NMN daily at a recommended dosage of one gram alongside resveratrol intake, individuals may experience improvements in insulin sensitivity and overall health. NMN supplementation, when consistent and monitored, can lead to increased NAD levels, potentially enhancing longevity and combating the effects of aging.

  • How can individuals monitor and improve their biological age?

    Monitoring and measuring biological age is crucial to assess the effectiveness of lifestyle changes in promoting longevity and overall health. A biological age test, involving a simple mouth swab, is being developed to predict future health and lifespan. By taking the test and receiving personalized health scores and recommendations, individuals can make informed decisions about their well-being. The goal is to democratize the test, empowering individuals to understand their biological age and take steps to potentially reverse aging by making positive changes in their lifestyle.

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Summary

00:00

"Unlocking Aging Secrets: Lifespan Podcast Launch"

  • The Huberman Lab podcast discusses science and science-based tools for everyday life, hosted by Andrew Huberman, a neurobiology and ophthalmology professor at Stanford School of Medicine.
  • Dr. David Sinclair, a genetics professor at Harvard Medical School, focuses on understanding aging and ways to slow or reverse its effects by studying cellular and molecular pathways.
  • Dr. Sinclair's research identifies intervention points through behavioral, nutritional, supplementation, and prescription drug methods to combat aging effects.
  • Aging is viewed as a disease by Dr. Sinclair, who believes it can be slowed or halted, contrary to it being a natural consequence.
  • Dr. Sinclair's work emphasizes public education on aging biology and interventions, including his New York Times bestseller book 'Lifespan: Why We Age And Why We Don't Have To.'
  • Dr. Sinclair is launching the 'lifespan podcast' on January 5th, 2022, focusing on aging biology and intervention tools, available on various platforms.
  • The podcast aims to educate on the mechanistic science behind aging, reversing aging, and practical tools for daily life.
  • Sponsors of the podcast include ROKA for eyeglasses and sunglasses, InsideTracker for personalized nutrition analysis, and Magic Spoon for zero sugar, keto-friendly cereal.
  • Dr. Huberman and Dr. Sinclair discuss aging, longevity, and actionable protocols to increase lifespan, emphasizing aging as a disease that can be reversed by addressing its underlying causes.
  • The epigenome, a crucial aspect of aging, is highlighted as a major factor that can be adjusted positively to combat aging effects.

12:12

"Gene expression and aging: a crucial link"

  • Aging is equated to the loss of information due to entropy, a challenge linked to the second law of thermodynamics.
  • Aging is described as a loss of information, akin to losing data when copying or transmitting information.
  • Genetic information (ATCG) and epigenetic information (control systems for gene expression) are crucial for longevity and health.
  • The epigenome controls gene expression, akin to a DVD reader playing specific songs in cells.
  • Aging is compared to scratching a CD or DVD, leading to cells malfunctioning due to incorrect gene expression.
  • DNA, six feet long when stretched, is carefully wrapped to control gene expression through chemical markings.
  • Chemical markings on DNA dictate cell type and function, with aging causing disruptions in gene expression.
  • Changes in gene expression due to aging can be measured and predict lifespan based on chemical alterations.
  • Slower development during puberty may indicate a longer, healthier life, possibly linked to growth hormone levels.
  • Epigenetic changes due to lifestyle choices can modify gene expression, impacting longevity more than genetic factors.

25:40

"Intermittent Fasting: Key to Longevity"

  • In the early 20th century, the concept of restricting calories for longevity was discovered but overlooked by people.
  • In the 1930s, Claude McKay conducted an experiment with rats, adding cellulose to their food to limit calorie intake, resulting in the rats living 30% longer.
  • Longevity genes, such as sirtuins, were found to be activated by low levels of insulin and insulin-like growth factor, particularly SIRT1.
  • Constant high levels of insulin from continuous feeding prevent the activation of longevity genes, leading to faster aging.
  • Lack of glucose triggers major muscles in the brain to become more sensitive to insulin, aiding in preventing type two diabetes.
  • Studies suggest that periods of hunger, rather than actual hunger, trigger the body to activate defensive genes for longevity.
  • Research by Rafael de Cabo showed that mice living longer were those with restricted eating windows, regardless of diet composition.
  • Skipping a meal a day is recommended as a starting point for intermittent fasting, preferably at the beginning or end of the day.
  • Longer fasting periods, such as 48 or 72 hours, can trigger autophagy, a process that cleanses the body of old and misfolded proteins.
  • Activation of sirtuins and down-regulation of mTOR through fasting are crucial for triggering the body's defense mechanisms for longevity.

38:04

"Leucine's Impact on Aging and Longevity"

  • Leucine is a topic of debate due to protein intake discussions and its impact on the mTOR pathway.
  • Many individuals aim to consume more leucine regularly for wellness, fitness, and muscle growth.
  • Leucine's role in triggering cell growth may have implications for aging.
  • Supplementing with growth hormone or testosterone may offer immediate benefits but could compromise long-term health.
  • A protocol involving intermittent fasting, supplements, and exercise has been developed over 15 years.
  • Ori Hofmekler, known for the Warrior Diet and intermittent fasting, emphasizes nourishing pulses for vitality.
  • Pulsing nutrition and exercise can prompt cells to perceive adversity, potentially slowing aging.
  • Resveratrol supplementation every other day significantly extended the lifespan of mice.
  • Metformin, a longevity drug, is taken daily in the morning, skipped on exercise days for better performance.
  • Berberine, a Metformin alternative, may enhance energetics and insulin sensitivity, but caution is advised based on limited worm data.

51:03

Optimizing Longevity with Resveratrol and NMN

  • Resveratrol supplementation is recommended at a dosage of a thousand milligrams per day, ideally obtained from a pure supplement that is light gray or white in color to avoid contamination.
  • Resveratrol should be ingested with a fatty substance like olive oil or yogurt to enhance absorption, as it may not be effective if taken with water alone.
  • Incorporating oleic acid from olive oil alongside resveratrol is beneficial for activating sirtuin defenses, with a suggested method of mixing the supplement with olive oil, Coresatin, vinegar, and basil leaf for improved absorption.
  • Philosophically, enjoying life is emphasized, and minor caloric intake like olive oil or yogurt is not believed to negatively impact longevity pathways, especially when followed by a prolonged fasting period.
  • Gradual dietary changes are recommended over abrupt shifts, akin to quitting smoking, to facilitate habit adaptation and long-term success.
  • NMN and NR are highlighted as molecules that impact the sirtuin pathway and aging rates, with NMN serving as a precursor to NAD, crucial for sirtuin activation and cellular functions.
  • NMN supplementation at a dosage of one gram daily is suggested, alongside resveratrol intake, with personal variations in response to supplements due to individual factors like microbiome and age.
  • NR, a form of vitamin B3, is less effective in increasing NAD levels compared to NMN, as it lacks the necessary components for NAD synthesis, making NMN a more efficient choice.
  • Dosage consistency and personal monitoring of biomarkers are emphasized to gauge the effectiveness of NMN supplementation, with observed increases in NAD levels by two-fold or more in individuals following the recommended protocol.
  • Individual responses to supplementation may vary, necessitating personalized adjustments based on factors like microbiome composition and age, despite general guidelines provided.

01:03:44

"Optimizing Health with NMN and Bloodwork"

  • NMN should be taken daily at a dosage of 1000 milligrams.
  • Look for NMN from reputable companies with high-quality control standards, indicated by the GMP label.
  • NMN should be white and crystalline in appearance, with a taste resembling burnt popcorn.
  • NMN, along with resveratrol and Metformin, should be consumed in the morning due to the natural NAD cycle in the body.
  • Taking NMN late at night can disrupt circadian rhythms.
  • An increase in NAD levels after two weeks of consumption may lead to improved insulin sensitivity.
  • Iron supplements may accelerate aging by increasing senescent cells in the body.
  • Personalized medicine is crucial, as individuals may have different baseline levels of biomarkers like iron and ferritin.
  • Regular blood work tracking is essential for understanding how supplements, diet, and exercise impact health.
  • Understanding blood work data requires tracking over time and looking beyond standard red, yellow, or green ranges to identify optimal health markers.

01:16:31

"Unlocking Health Secrets with InsideTracker Data"

  • David educates his physician using data from InsideTracker, showing changes in his cholesterol and CRP levels.
  • Physicians appreciate data but may not have access due to insurance limitations.
  • David suggests using a code word like "WTH" to trigger comprehensive blood tests.
  • People deserve to know their health status and can use companies like InsideTracker for tests.
  • Essential blood tests include blood sugar levels, HbA1c, and CRP for inflammation.
  • CRP is crucial for predicting heart disease and longevity, affected by diet and age.
  • Cholesterol's impact on health is complex, with dietary cholesterol having minimal effect on blood levels.
  • Statins can help manage cholesterol levels, but potential side effects should be considered.
  • A new drug, PCSK9 inhibitor, shows promise in lowering cholesterol and may have longevity benefits.
  • Plants offer high nutrition and xenohormetic molecules that activate health defenses, making them beneficial for overall health.

01:29:08

"Antioxidants, Exercise, and Supplements for Longevity"

  • Resveratrol and quercetin are supplements that mimic the effects of activating sirtuins and killing senescent cells.
  • Antioxidants are beneficial in moderation, as they are necessary for the immune system and mitochondrial function.
  • Overdosing on antioxidants like vitamin C and E can be harmful, as they disrupt the body's natural defenses against aging.
  • Taking multivitamins unnecessarily can be detrimental, especially in the case of iron and antioxidants.
  • Antioxidants, like catalase and superoxide dismutase, have not shown significant longevity benefits in animals and humans.
  • Resveratrol's longevity benefits are not due to its antioxidant properties but its ability to activate the body's defenses against aging.
  • Aerobic exercise in mice and rats increases NAD levels and sirtuin gene expression, but the optimal exercise type for humans is still being researched.
  • Maintaining muscle mass through exercise is crucial for hormone levels and overall health, especially in older individuals.
  • Fasting and caloric restriction can delay aging and infertility in female animals by activating sirtuins.
  • NMN supplementation has shown to rejuvenate the reproductive system in old mice, challenging traditional beliefs about female fertility.

01:42:11

"Gene therapy reverses blindness, rejuvenates body"

  • Neurons in the eye can be reversed in age and protected from damage, allowing blind mice to regain sight and prevent degeneration.
  • Human clinical trials are planned, starting with testing on monkeys for safety, with the first patient expected in 2022 or early 2023.
  • Treatment involves injecting a virus into the eye to manipulate transcription factors, aiming to recover blindness.
  • Research at Harvard focuses on gene therapy to rejuvenate the body, potentially through a pill that can turn on genes in the eye and other areas.
  • A single injection into the eye can activate genes in the retina, leading to rejuvenation and restored vision in mice.
  • The treatment is painless when done by a professional, with genes staying in the eye permanently and able to be turned on and off as needed.
  • The potential for this treatment to be applied across the entire body, with the ability to reset and repeat the process every five years.
  • Affordable technology for at-home tumor detection is still in progress, with some companies offering blood tests for circulating DNA to detect cancer.
  • At-home colon cancer tests are available for around $100, providing accurate results comparable to a colonoscopy.
  • Obesity can reduce NAD levels and accelerate aging due to the presence of senescent cells in fat, which secrete inflammatory molecules that contribute to aging.

01:54:21

"Biological Age Testing: Empowering Health Decisions"

  • Methylation can affect the epigenome by attaching to genes incorrectly, leading to issues like aging.
  • Monitoring and measuring biological age is crucial to assess the effectiveness of lifestyle changes.
  • A device can measure body temperature, movement, heart rate variability, and even detect potential health issues like colds or heart attacks.
  • Avoiding x-ray scanners at airports is recommended, and opting for a pat-down or TSA Pre can be alternatives.
  • Limiting dental x-rays due to cumulative radiation exposure is advised, with lead protection being essential.
  • Public health education efforts are vital to bridge the gap in understanding and provide trustworthy information.
  • Scientists are now able to communicate directly with the public, offering accurate and reliable information.
  • A biological age test is being developed to predict future health and lifespan, aiming to make it more accessible and affordable.
  • The test will provide personalized health scores and recommendations to improve overall health and longevity.
  • The goal is to democratize the test to empower individuals to make informed decisions about their health and well-being.

02:06:39

"Biological age test and anti-aging supplements"

  • A biological age test has been developed, involving a simple mouth swab, and is being rolled out. Interested individuals can sign up at doctorsinclair.com to be among the first to take the test and see the results.
  • Those who manage to reduce their biological age by a year or more may receive a negative birthday card from Dr. David Sinclair, with the goal of eventually being able to reverse aging by up to 20 years.
  • Thorne Supplements are recommended for those interested in supplements, as they are of the highest quality and precision, with a 20% discount available at thorne.com/u/huberman. The launch of the Lifespan podcast featuring Dr. David Sinclair is set for January 5th, offering valuable insights on aging and longevity.
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