November 5, 2018


David Sinclair, Ph.D.: Slowing aging – sirtuins, NAD, and the epigenetics of aging (EP.27)

“This is a lesson for anyone who's listening who thinks that getting to somewhere like this is easy. You have to be massively determined, you have to have grit, and I just wouldn't give up because there's nothing else I want to do in my life.” —David Sinclair

by Peter Attia

Read Time 15 minutes

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.


We discuss:

  • How and why David moved from Australia to Lenny Guarente’s lab at MIT [7:30];
  • Sirtuins and aging [15:00];
  • A series of experiments elucidating the mechanisms of sirtuins [20:45];
  • How are sirtuins activated? [25:30];
  • NAD and sirtuin activation [31:00];
  • Nicotinamide, sirtuin inhibition, and PNC1 [39:00];
  • Resveratrol [43:00];
  • The NIH/ITP studies on resveratrol [55:45];
  • Does David take any compounds for longevity? [1:00:15];
  • NAD precursors (NR, NMN) and pterostilbene [1:02:45];
  • Female fertility and NAD precursors [1:14:45];
  • A unifying theory of aging [1:20:30];
  • Waddington’s epigenetic landscape [1:23:00];
  • If David had unlimited resources, what is the experiment he would do? [1:28:25];
  • Testing combinations to extend lifespan [1:31:30];
  • What made David aware of his mortality at such a young age? [01:33:45];
  • What is David’s book going to cover? [01:37:15]; and
  • More.


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(Boston, MA - 3/23/17) David Sinclair, director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School, discovered how to reverse aging in mice, Thursday, March 23, 2017. Staff photo by Angela Rowlings.

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