← The Peter Attia Drive

#27 - David Sinclair, Ph.D.: Slowing aging – sirtuins, NAD, and the epigenetics of aging

Nov 5, 2018 1h 41m 18 insights
<p>In this episode, David A. 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, provides insight into why we age and how to slow its effects based on his remarkable work on the role of sirtuins and NAD in health and diseases. He also presents the case that stabilizing the epigenetic landscape may be the linchpin in counteracting aging and disease. </p> <p>We discuss:</p> <ul> <li>How and why David moved from Australia to Leonard Guarente's lab at MIT [<a href="">7:30</a>];</li> <li>Sirtuins and aging [<a href="">15:00</a>];</li> <li>A series of experiments elucidating the mechanisms of sirtuins [<a href="">20:45</a>];</li> <li>How are sirtuins activated? [25:30];</li> <li>NAD and sirtuin activation [31:00];</li> <li>Nicotinamide, sirtuin inhibition, and<em>PNC1</em> [39:00];</li> <li>Resveratrol [43:00];</li> <li>The NIH/ITP studies on resveratrol [55:45];</li> <li>Does David take any compounds for longevity? [1:00:15];</li> <li>NAD precursors (NR, NMN) and pterostilbene [1:02:45];</li> <li>Female fertility and NAD precursors [1:14:45];</li> <li>A unifying theory of aging [1:20:30];</li> <li>Waddington's epigenetic landscape [<a href="">1:23:00</a>];</li> <li>If David had unlimited resources, what is the experiment he would do? [1:28:25];</li> <li>Testing combinations to extend lifespan [1:31:30];</li> <li>What made David aware of his mortality at such a young age? [01:33:45];</li> <li>What is David's book going to cover? [01:37:15]; and</li> <li>More.</li> </ul> <p> <span> Learn more at <a href="http://www.peterattiamd.com/"><span><u>www.PeterAttiaMD.com</u></span></a></span></p> <p> <span>Connect with Peter on <a href=""> <span> <u>Facebook</u></span></a> | <a href=""> <span> <u>Twitter</u></span></a> | <a href=""> <span> <u>Instagram</u></span></a>.</span></p>
Actionable Insights

1. Avoid High-Dose Nicotinamide

Avoid taking really high doses of nicotinamide (Vitamin B3) as it acts as an inhibitor of sirtuins, which are important for longevity pathways.

2. Review Rabinowitz NAD Paper

Consult the Josh Rabinowitz paper in Cell Metabolism (linked in show notes) for a potentially compelling case regarding the futility of orally administered NAD precursors.

3. Enhance Resveratrol Absorption

Take resveratrol with a fatty food, such as oil or yogurt, to significantly improve its absorption and increase blood levels.

4. Cautious Supplement Stacking

When combining multiple longevity-focused molecules like metformin and resveratrol, start with a reasonable low dose and gradually increase, monitoring well-being and blood tests due to potential additive effects and unknown interactions.

5. Prioritize NAD Precursors

Prioritize NAD precursors (like NMN or NR) over single sirtuin activators (like resveratrol) for broader activation of all seven sirtuins and to replenish age-related NAD decline, as NMN has shown lifespan extension in wild-type mice.

6. Consider Expert’s Personal Regimen

Consider David Sinclair’s personal regimen of taking resveratrol, metformin, and NMN, acknowledging it’s an individual experiment based on available data for potential health benefits.

7. Beware Unendorsed Supplements

Do not trust over-the-counter supplements that claim to be endorsed by David Sinclair, as he does not endorse any products.

8. Store NAD Precursors Cold

Store NAD precursors like NMN and NR in the freezer to maintain their stability and extend their shelf life.

9. Scrutinize NAD Precursor Claims

Recognize that claims of significant performance improvement from NAD precursors (NR/NMN) are currently anecdotal and lack placebo-controlled evidence, requiring caution.

10. Understand NAD Measurement Complexity

Understand that measuring NAD precursor effects is complex; blood levels don’t necessarily reflect tissue uptake or activity, and advanced studies are ongoing to clarify distribution.

11. Cultivate Grit and Determination

Develop massive determination and grit, as demonstrated by David Sinclair’s career path, to overcome challenges and achieve ambitious life goals.

12. Advocate for Longevity Trials

Advocate for or support large-scale human clinical trials (e.g., 5,000 people in their 70s for 3-4 years) to definitively assess the impact of longevity drugs on mortality rates.

13. Read David Sinclair’s Book

Look for David Sinclair’s book, expected in late summer/early fall 2019, for a comprehensive understanding of aging, his universal hypothesis, and societal implications.

14. Explore Peter Attia’s Website

Visit peteratiyahmd.com for more information on episodes, show notes, blog posts, and the ’nerd safari'.

15. Sign Up For Weekly Email

Head to PeterTiaMD.com to sign up for Peter Attia’s weekly email list for updates on longevity, science, performance, and sleep.

16. Follow David Sinclair Online

Follow David Sinclair on Twitter (@DavidASinclair) or LinkedIn to communicate and stay updated on his work.

17. Follow Peter Attia Online

Follow Peter Attia on Twitter (@peteratiamd) for questions, comments, and updates.

18. Review Podcast on iTunes

Leave a review on iTunes for the podcast, whether positive or constructive, to provide feedback and support.