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Huberman Lab
Dr. David Sinclair: The Biology of Slowing & Reversing Aging
Dec 27, 2021
02:07:56
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Quick takeaways
- Fasting activates longevity genes and triggers autophagy, leading to a slow down in the aging process.
- Supplementation with resveratrol and berberine can have potential anti-aging benefits.
- Pulsing, alternating periods of nourishment and rest, can optimize the effects of exercise, supplements, and meals.
- Longevity practices require individual experimentation and customization to find the optimal balance.
- Sirtuins, crucial proteins for maintaining the body, can be activated through exercise, fasting, and the consumption of resveratrol and NAD precursors like NMN.
Deep dives
Fasting and its Impact on Longevity
Fasting, specifically by skipping a meal a day, has been found to activate longevity genes and slow down the aging process. This is because fasting leads to low blood sugar and insulin levels, which in turn activate sirtuin genes. It also triggers the autophagy system, which helps clear out old and misfolded proteins in the body. To incorporate fasting into your routine, you can skip breakfast or dinner, depending on your preference. Fasting for longer periods, like 48 or 72 hours, can further extend the benefits of longevity. It is suggested to drink fluids like water, tea, or coffee during fasting periods to maintain hydration. It is important to listen to your body and adjust the fasting protocol to suit your individual needs and preferences.
The Power of Resveratrol and Berberine
Resveratrol, a compound found in red wine, and berberine, a substance from tree bark, both have potential anti-aging benefits. However, it is not practical to consume sufficient amounts of resveratrol from red wine alone, so supplementation is recommended. Taking approximately 1000 milligrams of pure resveratrol per day, preferably with a fatty substance like olive oil or yogurt, has been found effective in numerous studies. Berberine, often referred to as the 'poor man's metformin,' is believed to have similar effects on longevity pathways. Berberine may help improve insulin sensitivity and metabolic health. It is advised to take berberine with meals or dissolve it in a liquid. It is always recommended to consult with a healthcare professional before starting any new supplementation regimen.
Pulsing and Timing for Optimal Results
Pulsing means giving the body periods of nourishment followed by rest, and it has shown positive effects on longevity. For example, taking resveratrol, metformin, or berberine on alternate days instead of every day may be beneficial. Timing is crucial for maximizing the benefits of exercise, supplements, and meals. For exercise, skipping metformin on workout days is suggested. A meal timing strategy involves a fasting window during the day followed by a nutritious dinner. It is important to find a routine that works for you and aligns with your goals, preferences, and individual needs. Making gradual changes and listening to your body is key for long-term success.
Individual Variations and Personal Optimization
Optimizing longevity practices requires individual experimentation and finding a balance that works best for you. Markers of success, such as enjoying life and feeling vitality, should be considered alongside longevity outcomes. Personal variations play a role in designing an optimal protocol. For instance, some individuals may need to adjust fasting windows, supplement timing, or consider additional factors like exercise and specific dietary choices. Monitoring your body's response and adjusting accordingly are essential. It is important to consult with healthcare professionals and stay informed about scientific research in order to make informed decisions regarding supplementation and longevity practices.
Effects of Exercise and Fasting on Sirtuins
Exercise and fasting both naturally enhance the activity of sirtuins, which are genes that produce proteins responsible for maintaining the body. Another way to activate sirtuins is through the consumption of resveratrol, a compound found in red wine. However, sirtuins also require a molecule called NAD for optimal function. NAD levels can decline with obesity, aging, and lack of hunger, leading to reduced sirtuin activity. Taking a precursor to NAD called NMN can increase NAD levels, enhancing the benefits of sirtuin activation.
The Role of NAD in Aging and Health
NAD is a crucial molecule involved in hundreds of chemical reactions in the body. However, NAD levels decline with age, obesity, and lack of hunger. Lower NAD levels can compromise the function of sirtuins, which rely on NAD for their activity. To maintain youthful sirtuin defenses, it is essential to boost NAD levels. Taking NAD precursors like NMN or NR can effectively increase NAD levels and support the longevity-promoting effects of sirtuins.
The Benefits of Anamen as an NAD Precursor
Anamen is a precursor to NAD that can be taken as a supplement to increase NAD levels in the body. Clinical trials have shown that taking anamen for about two weeks can double NAD levels in the blood. This increase in NAD can have various positive effects on energy, focus, and vitality. To ensure the quality of the supplement, it is advisable to look for products from companies that follow Good Manufacturing Practices (GMP) and undergo rigorous quality control measures.
Harnessing the Power of Stressed Plants
Plants under stress produce molecules that promote health and longevity. These molecules, called xenohormetic molecules, are activated when plants are exposed to stressors like lack of water or pest attacks. Resveratrol, found in grapes and wine, is one such molecule. Consuming plants that have experienced stress and taking supplements like resveratrol mimic the effects of activating our own defenses.
Reevaluating the Role of Antioxidants
The belief that antioxidants are the key to longevity has been challenged. While antioxidants are important for our immune system and mitochondrial function, excessive intake may be harmful. Research has shown that simply taking antioxidants does not provide the desired longevity benefits. Instead, turning on the body's natural defenses, like the sirtuin genes, is more effective. The focus should be on maintaining muscle mass, promoting hormone levels, and following healthy lifestyle behaviors.
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In this episode, I am joined by Dr. David Sinclair, tenured Professor of Genetics at Harvard Medical School and an expert researcher in the field of longevity. Dr. Sinclair is also the author of the book Lifespan: Why We Age & Why We Don't Have To, and the host of the Lifespan Podcast, which launches January 5, 2022.
In this interview, we discuss the cellular and molecular mechanisms of aging and what we all can do to slow or reverse the aging process. We discuss fasting and supplementation with resveratrol, NAD, metformin, and NMN. We also discuss the use of caffeine, exercise, cold exposure, and why excessive iron load is bad for us. We discuss food choices for offsetting aging and promoting autophagy (clearance of dead cells). And we discuss the key blood markers everyone should monitor to determine your biological versus chronological age. We also discuss the future of longevity research and technology. This episode includes lots of basic science and specific, actionable protocols, right down to the details of what to do and when. By the end, you will have in-depth knowledge of the biology of aging and how to offset it.
Read the full show notes for this episode at hubermanlab.com.
Thank you to our sponsors
AG1: https://athleticgreens.com/huberman
LMNT: https://drinklmnt.com/hubermanlab
Waking Up: https://wakingup.com/huberman
Momentous: https://livemomentous.com/huberman
Timestamps
00:00:00 Dr. David Sinclair, Harvard Medical School
00:03:45 Sponsors: AG1, LMNT & Waking Up
00:07:45 “Aging as a Disease” vs. Longevity & Anti-Aging
00:10:23 What Causes Aging? The Epigenome
00:15:53 Cosmetic Aging
00:17:15 Development Never Stops, Horvath Clock
00:20:12 Puberty Rate as a Determinant of Aging Rate
00:23:00 Fasting, Hunger & Food Choices
00:32:44 Fasting Schedules, Long Fasts, (Macro)Autophagy
00:34:50 Caffeine, Electrolytes
00:35:56 Blood Glucose & the Sirtuins; mTOR
00:37:55 Amino Acids: Leucine, “Pulsing”
00:44:35 Metformin, Berberine
00:50:29 Resveratrol, Wine
00:53:20 What Breaks a Fast?
00:56:45 Resveratrol, NAD, NMN, NR; Dosage, Timing
01:09:10 Are Artificial Sweeteners Bad for Us?
01:12:04 Iron Load & Aging
01:15:05 Blood Work Analysis
01:19:37 C-Reactive Protein, Cholesterol: Serum & Dietary
01:26:02 Amino Acids, Plants, Antioxidants
01:33:45 Behaviors That Extend Lifespan, Testosterone, Estrogen
01:40:35 Neuroplasticity & Neural Repair
01:46:19 Ice Baths, Cold Showers, “Metabolic Winter”
01:48:07 Obesity & How It Accelerates Aging, GnRH
01:52:10 Methylation, Methylene Blue, Cigarettes
01:56:17 X-Rays
01:59:00 Public Science Education, Personal Health
02:05:40 The Sinclair Test You Can Take: www.doctorsinclair.com
02:08:13 Zero-Cost Support & Resources, Sponsors, Supplements, Instagram
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