<p>In this episode, David Sinclair, Ph.D., a Professor in the Department of Genetics at Harvard Medical School and co-Director of the Paul F. Glenn Center for the Biological Mechanisms of Aging, returns to the podcast to discuss the content of his new book, Lifespan: Why We Age - and Why We Don't Have To. This conversation focuses on the biological mechanisms involved in what David terms the Information Theory of Aging which provides insights into the "clock" that determines our aging and to what degree it can be manipulated. Our discussion on aging of course leads us into interconnected topics of epigenetics, sirtuins, cellular senescence, as well as what compounds David is personally taking for his own longevity. Additionally, we discuss the most up to date information related to NAD and longevity by looking at the potential benefits (if any) of supplemental agents (NAD precursors, NR, NMR, etc.) that pose a promise of increasing NAD.</p> <p><span style="color: #333333;">We discuss:<br /></span></p> <ul> <li><span style="color: #333333;">SIR genes and cellular identity [<a href="">8:45</a>];<br /></span></li> <li><span style="color: #333333;">Sirtuins regulate gene expression [<a href="">14:30</a>];<br /></span></li> <li><span style="color: #333333;">DNA is methylated at the deepest layer of the epigenome [<a href="">17:45</a>];<br /></span></li> <li><span style="color: #333333;">Methylation pattern and determining cellular age [<a href="">20:15</a>];<br /></span></li> <li><span style="color: #333333;">Cellular reprogramming [33:45];<br /></span></li> <li><span style="color: #333333;">Yamanaka factors to push cells "back in time" [41:00];<br /></span></li> <li><span style="color: #333333;">Human cellular reprogramming viability [57:00];<br /></span></li> <li><span style="color: #333333;">Measuring the rate of aging [1:02:45];<br /></span></li> <li><span style="color: #333333;">Cellular reprogramming for longevity [1:14:45];<br /></span></li> <li><span style="color: #333333;">Compounds David takes for his own longevity [1:29:15]<br /></span></li> <li><span style="color: #333333;">NAD precursors (NR, NMN) and pterostilbene [<a href="">1:40:00</a>];<br /></span></li> <li><span style="color: #333333;">The current field of sirtuin activators [2:03:15];<br /></span></li> <li><span style="color: #333333;">David's artistic work [2:05:15] and;<br /></span></li> <li><span style="color: #333333;">More.</span></li> </ul> <p>Learn more: <a href="https://peterattiamd.com/">https://peterattiamd.com/</a><br /> <br /> Show notes page for this episode:<a href="https://peterattiamd.com/davidsinclair2/"><span style="color: #333333;">https://peterattiamd.com/davidsinclair2/</span></a><br /> <br /> Subscribe to receive exclusive subscriber-only content: <a href="https://peterattiamd.com/subscribe/">https://peterattiamd.com/subscribe/</a><br /> <br /> Sign up to receive Peter's email newsletter: <a href="https://peterattiamd.com/newsletter/">https://peterattiamd.com/newsletter/</a><br /> <br /> Connect with Peter on <a href="http://Facebook.com/PeterAttiaMD"><u>Faceboo</u></a><u>k</u> | <a href="http://Twitter.com/PeterAttiaMD"><u>Twitter</u></a> | <a href="http://Instagram.com/PeterAttiaMD"><u>Instagram</u></a>.</p>
Actionable Insights
1. Slow Epigenetic Aging
Engage in regular exercise and calorie restriction, and avoid smoking, as these actions are known to slow down your biological (epigenetic) clock.
2. Fast to Boost NAD
Practice fasting (e.g., for a couple of days) to increase NAD levels, which helps sirtuins repair DNA and maintain gene silencing, thereby slowing the aging clock.
3. Pulse Biological Stress
Apply biological stressors (like exercise or certain supplements) in a pulsatile manner, allowing the body adequate time to recover and adapt, rather than continuous exposure.
4. Pulse Rapamycin Dosing
If taking rapamycin, use a pulsatile dosing schedule rather than daily, and avoid taking it around exercise to prevent blunting muscle growth and healing.
If taking metformin, avoid taking it on days of intense exercise and potentially the day after, to allow your body to recover and build up mitochondria without inhibition.
Consider taking metformin during periods of inactivity, such as long trips with limited exercise, and lay off it when you are regularly exercising.
7. NAD Boosters for Unhealthy
If you are metabolically unhealthy, obese, or have a disease, NAD boosters (like NR or NMN) may offer more significant benefits by replenishing lost NAD levels.
8. Avoid High-Dose Nicotinamide
Avoid taking high doses of nicotinamide (NAM) unless for specific medical reasons (e.g., cancer), as it can inhibit sirtuins, which are enzymes you want to keep active for longevity.
9. Prefer NR/NMN over Niacin
If your goal is to effectively raise NAD levels, consider taking nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN) rather than high doses of niacin (vitamin B3), as NR/NMN are more effective in mice.
10. Consider Higher NR Dose
A recent human study used 1000mg of oral NR (four times the typical supplement dose) to successfully raise NAD levels in muscle, suggesting a higher dose might be needed for systemic effects.
11. Take Resveratrol with Fat
If taking resveratrol, consume it with a fatty meal (e.g., yogurt) to potentially enhance its absorption and effectiveness.
12. Resveratrol for Unhealthy Diet
Consider resveratrol supplementation if consuming a Western diet, as it has been shown to extend the lifespan of mice on such a diet.
13. Consider Daily Resveratrol
David Sinclair takes 1 gram of resveratrol every morning, noting it’s a high dose but seems fine for him and he keeps it constant in his regimen.
14. Monitor Biological Age
Consider getting your DNA methylome (Horvath clock) measured every 6-12 months to track your biological aging rate and assess the directional correctness of your lifestyle interventions.
15. Find DNA Methylation Service
Search for companies online that offer DNA methylation age testing to determine your biological age.
16. Read “Lifespan” Book
Read David Sinclair’s book “Lifespan” for a deep, technical understanding of the information theory of aging and related concepts.
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