Published December 2021 on YouTube

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

1. Aging Interventions

Dr. David shares his revolutionary view that aging is a disease that can be slowed or halted. He talks about the behavioral interventions, nutritional interventions, supplementation, and prescription drug interventions that can help us all age more slowly and reverse the effects of aging in all tissues of the body.+

2. ROKA, InsideTracker, Magic Spoon

Science and Health:Andrew talks about science and health, and how Roca and Inside Tracker can help you achieve your health goals. He emphasizes the importance of regular blood work and how Inside Tracker can help you understand your body better. He also talks about Roca's eyeglasses and sunglasses, which are designed to be worn during various activities and always provide clarity.+
Health and Nutrition:Andrew shares his approach to health and nutrition, including his fasting routine and favorite keto-friendly snack, Magic Spoon cereal. He also introduces a discount code for Inside Tracker and Magic Spoon.+

3. Aging as a Disease

David explains the difference between the terms longevity, antiaging, and aging as a disease. He argues that aging should be considered a disease because it is the root cause of many common diseases such as heart disease and Alzheimer's. He emphasizes the importance of slowing down aging and reversing the age of the body to prevent and treat these diseases.+

4. What Causes Aging? The Epigenome

Aging's Hallmarks:David explains that aging has eight or nine major causes called hallmarks, with the epigenome being the most significant. He also discusses how aging is a loss of information due to entropy and how 80% of our future longevity and health is controlled by the epigenetic information.+
DNA Scratches:David and Andrew discuss the concept of DNA scratches, which occur due to disruptions in the epigenome, leading to the loss of cell identity and function, and ultimately aging. They explain how DNA is marked with chemicals that dictate which genes are switched on and off, and how these marks change over time. David also shares how measuring these changes can predict when someone is going to die.+

5. Cosmetic Aging

Andrew and David discuss the relationship between DNA scratches and aging, specifically the physical manifestations of aging such as wrinkles and drooping skin. David explains that centenarian families tend to look younger than their age and that an AI system can accurately predict someone's age based on their facial features.+

6. Aging and Development

Andrew and David discuss how development doesn't stop at a certain age and how the early stages of life and puberty are rapid stages of aging. They also talk about the Horvath clock and how it can predict biological age. David explains how broken chromosomes and massive cell damage can accelerate aging and how they can control aging in mice.+

7. Puberty and Aging

Andrew and David discuss the relationship between puberty and aging. They explore how the rate of entry into and through puberty can predict overall rates of aging, and how growth hormone plays a role in this. They also mention how caloric restrictions and dwarf mutations can lead to longer, healthier lives.+

8. Fasting, Hunger & Food Choices

Longevity Secrets:David explains how the idea of never being hungry is a big mistake and why the ones that live the longest are the ones that don't eat all the time. He also talks about how the epigenome can change and how you can have a bigger impact on your life than anything your genes give you.+
Hunger and Longevity:David Sinclair discusses how periods of hunger can activate longevity genes in the body, leading to a longer lifespan. He also mentions studies that simulate the effects of hunger while still providing calories and how it can activate the body's defensive genes.+
Intermittent Fasting Benefits:David shares his protocol for intermittent fasting, suggesting that skipping a meal a day is the best way to start. He recommends skipping breakfast and filling up on liquids throughout the day. David believes that it's not as important what you eat, but when you eat during the day.+
Diet and Productivity:David and Andrew discuss the impact of diet on productivity. David shares how regulating his blood sugar levels through a mostly vegetable-based diet has given him pure focus throughout the day. He also avoids sugar and simple carbohydrates to prevent plaque buildup in his mouth. However, what works for him may not be perfect for everyone.+

9. Long Fasting Benefits

David Sinclair discusses the benefits of longer fasting periods, including triggering the autophagy system which digests old and misfolded proteins in the body. He mentions a deep cleanse called Chaperone mediated autophagy which kicks in on day two or three of fasting and can increase longevity by 35% in old mice.+

10. Caffeine, Electrolytes

Andrew and David discuss the need for electrolytes during fasting. While David doesn't see a need for it, he acknowledges that it makes sense for those who experience lightheadedness or shakiness.Show transcript +

11. Blood Glucose & the Sirtuins; mTOR

David explains how glucose and longevity mechanisms are tethered to each other, and how Sirtuins and Mtor pathways work together to activate the body's defenses, improve insulin sensitivity, and repair cells.+

12. Amino Acids: Leucine, “Pulsing”

Leucine and Longevity:David and Andrew discuss the effects of leucine on the body and its potential impact on longevity. David shares his protocol for building muscle and maintaining long-term health, which involves pulsing periods of fasting, exercise, and supplements. They also touch on the debate around supplementing with growth hormone or testosterone for immediate benefits versus long-term health.+
Pulsing for Vitality:David explains the importance of pulsing, or alternating periods of nourishment and restriction, to activate the body's defenses against aging. He shares his research on resveratrol, which showed that giving it to mice every other day on a normal diet dramatically extended their lifespan.+

13. Metformin, Berberine

Longevity Supplements:David shares his supplement regimen for longevity, including taking metformin and resveratrol in the morning and fasting each day. He advises taking metformin every other day to give the body a rest and timing it around exercise. Despite reducing stamina, metformin helps build strong muscles with lower inflammation and markers of aging.+
Metformin vs Berberine:David Sinclair and Andrew Huberman discuss the differences and similarities between metformin and berberine in terms of boosting energetics and increasing insulin sensitivity. While metformin is only available by prescription, berberine is known as the "poor man's metformin" and has been shown to be safe in humans. However, cautionary notes exist and people should talk to their doctor before adding or subtracting anything from their life.+

14. Resveratrol, Wine

David explains the importance of taking pure resveratrol supplements and the protocol for ingesting it with fatty substances like olive oil or yogurt. He also warns against contaminated resveratrol and emphasizes the need for dissolving it in something for better absorption.+

15. What Breaks a Fast?

David and Andrew discuss the rational approach to fasting and supplementation. They emphasize the importance of enjoying life and taking a gradual approach to fasting, rather than quitting cold turkey. They also touch on the topic of whether ingesting certain substances breaks a fast, and how the body only speaks in the language of glucose, ampk, mtor, etc.+

16. Anti-aging Supplements

Anti-aging Supplements:Andrew and David discuss molecules that impact the sirtuins pathway and how they can be incorporated into a supplementation protocol. They mention the importance of naturally boosting the activity of sirtuins through exercise and fasting, and also discuss the effectiveness of resveratrol and nad in activating sirtuins.+
Boosting NAD Levels:David explains the importance of NAD levels for maintaining youthfulness and how taking a precursor to NAD called Nmn can double NAD levels in the blood. He also compares Nmn and NR and shares his concerns about taking high doses of something that requires additional phosphate.+
Nmn Dosage:David shares his personal Nmn dosage and advises listeners to look for a well-established company with high levels of quality control when buying Nmn. He also emphasizes the importance of measuring oneself as different factors like microbiome, age, and sex can affect the effectiveness of Nmn.+
Nmn Protocol:David and Andrew discuss the Nmn protocol and its effects on anti-aging and energy levels. David explains the importance of taking the gram in the morning to maintain circadian rhythms and shares anecdotes from athletes who have seen improvements in their performance. Andrew plans to start taking Nmn and has seen positive effects on his sister who takes it regularly.+

17. Artificial Sweeteners

Andrew and David discuss the effects of artificial sweeteners on the gut microbiome and whether the perception of sweet taste can disrupt longevity pathways. David believes the negative effects are blown out of proportion and that the benefits of consuming artificial sweeteners outweigh the risks.+

18. Iron Load & Aging

Excess iron can accelerate the aging process by increasing the number of senescent cells in the body, which cause inflammation and can lead to cancer. Personalized medicine is needed to determine what is optimal for each individual's health.+

19. Blood Work Analysis

Tracking Health:David Sinclair emphasizes the importance of tracking health over time, stating that one measurement isn't enough. He highlights the value of having a decade or more of data and encourages people to educate themselves about the molecules on their blood work charts.+
Blood Work Benefits:David and Andrew discuss the benefits of getting regular blood work done, including tracking changes in cholesterol and inflammatory markers. They give tips on how to approach the conversation with your doctor and mention companies that offer affordable testing options.+

20. Cholesterol Confusion

Cholesterol Confusion:David and Andrew discuss the confusing literature on cholesterol, including the relationship between dietary and serum cholesterol, and the role of LDL and HDL in predicting mortality. They also touch on the importance of CRP as a marker for inflammation and its association with heart disease.+
Cholesterol Myths:David Sinclair debunks the myth that dietary cholesterol has a significant impact on blood cholesterol levels. He shares his experience with taking a statin since the age of 29 and how it has helped him manage his cholesterol levels. He also discusses new drugs like the psk nine inhibitor that can block the release of LDL from the liver and potentially prolong longevity.+

21. Amino Acids, Plants, Antioxidants

Plant Benefits:David and Andrew discuss the benefits of eating plants, including their high nutritional value and the presence of xenohormetic molecules that benefit health.+
Plant-based Defense:David Sinclair explains how resveratrol, a plant defense molecule, activates sirtuins genes in both plants and humans, and how consuming plants that have gone through stress can provide benefits. He also discusses the usefulness of antioxidants and the importance of not overdosing on them.+
Antioxidant Myth:David explains how antioxidants have failed to provide longevity benefits, and the importance of turning on the body's natural defenses against aging. Andrew highlights the importance of understanding the mechanism behind a process, rather than just modulating it.+

22. Modulating DNA Expression

Modulating DNA Expression:Andrew and David discuss the behavioral tools that can be used to modulate DNA expression and improve the sirtuins pathway, including aerobic and weight training. David emphasizes the importance of maintaining muscle mass to maintain hormone levels, including testosterone.+
Aging and Fertility:David Sinclair discusses how caloric restriction can delay infertility in female animals and how the sirtuins pathway can rejuvenate the female reproductive system. Andrew Huberman draws parallels between fertility and neuroplasticity, suggesting a potential correlation between the two.+

23. Neuroplasticity & Neural Repair

Reversing Aging:David and Andrew discuss the body's remarkable powers of healing and recovering from illness and injury, and how we can reverse the age of cells by telling them how to read genes correctly again. They also talk about reversing the age of neurons in the eye and how it can help recover blindness.+
Gene Therapy Potential:David and Andrew discuss the potential of gene therapy in anti-aging. David explains how a single injection of genes into the eye can rejuvenate the eye by 20 years and how it could potentially work in humans. Andrew mentions the painless nature of the injection and how it's a one-time treatment. They also touch on the possibility of using gene therapy across the entire body.+

24. Cold Exposure Benefits

David shares his hypothesis with Ray Cronus about the Metabolic Winter Hypothesis, which suggests that we rarely experience hunger or coldness nowadays. He explains that he tries to challenge his system to thermoregulate by sleeping cool and dressing lightly. He also talks about the benefits of cold exposure, including burning energy and compensating with changes in diet and exercise.+

25. Obesity and Aging

Andrew and David discuss the relationship between obesity and aging. David explains that obesity leads to an increase in senescent cells in fat, which secrete inflammatory molecules that accelerate aging. They also explore the potential connection between leptin and the Sirtuins pathway, and the role of the hypothalamus in regulating the body's age.+

26. Age Measurement Insights

Methylene Blue Misconceptions:David and Andrew discuss the misconceptions around ingesting methylene blue, a practice that some believe can extend lifespan. While it has been found to have benefits in lower organisms, the potential dangers and staining effects on the body make it a questionable practice for humans.+
Measuring Biological Age:David and Andrew discuss the importance of measuring biological age through epigenome methylation and the use of monitoring devices that can track a variety of health indicators in real-time. They emphasize the need to measure and track progress in order to optimize health and potentially reverse biological aging.+

27. X-Rays

David and Andrew discuss the dangers of X-rays, both at the airport and at the dentist. David shares his personal experience with limiting his exposure to X-rays and how he tries to avoid unnecessary scans. Andrew also mentions physicist Richard Feynman's concerns about the dangers of dental technology and X-rays.+

28. Science Education Revolution

Science Education Revolution:David and Andrew discuss the evolution of science education and the importance of public discourse in bridging the gap between scientists and the general public. They highlight the need for trusted sources of information and experts who can communicate complex ideas directly to the public.+
Scientists Speak:David and Andrew discuss the importance of scientists being able to speak to the public and the need for trustworthy sources of information in the midst of the pandemic. They also touch on the public's openness to health practices and the impact of 2020 on the thirst for knowledge.+

29. Biological Age Test

David discusses his lab's development of a biological age test that can predict future health and time of death. The test is a simple mouth swab that measures biological age and can be used to optimize health and longevity. He plans to democratize the test and create a system that will point people in the right direction and give discounts for certain things that will improve their health.+

30. Supplement Quality

Andrew discusses the importance of supplement quality and introduces Thorn as a trusted partner, offering listeners 20% off their supplements.+