Thursday, September 16, 2021
Mitochondrial Health Optimal Health

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

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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David Sinclair, Ph.D.

David A. Sinclair, Ph.D. is 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.

He is best known for his work on understanding why we age and how to slow its effects. He obtained his Ph.D. in Molecular Genetics at the University of New South Wales, Sydney in 1995. He worked as a postdoctoral researcher at M.I.T. with Dr. Leonard Guarente where he co-discovered a cause of aging for yeast as well as the role of Sir2 in epigenetic changes driven by genome instability. In 1999 he was recruited to Harvard Medical School where his laboratory’s research has focused primarily on understanding the role of sirtuins in disease and aging, with associated interests in chromatin, energy metabolism, mitochondria, learning and memory, neurodegeneration, and cancer. He has also contributed to the understanding of how sirtuins are modulated by endogenous molecules and pharmacological agents such as resveratrol.

Dr. Sinclair is co-founder of several biotechnology companies (Sirtris, Ovascience, Genocea, Cohbar, MetroBiotech, ArcBio, Liberty Biosecurity) and is on the boards of several others. He is also co-founder and co-chief editor of the journal Aging. His work is featured in five books, two documentary movies, 60 Minutes, Morgan Freeman’s “Through the Wormhole” and other media.

He is an inventor on 35 patents and has received more than 25 awards and honors including the CSL Prize, The Australian Commonwealth Prize, Thompson Prize, Helen Hay Whitney Postdoctoral Award, Charles Hood Fellowship, Leukemia Society Fellowship, Ludwig Scholarship, Harvard-Armenise Fellowship, American Association for Aging Research Fellowship, Nathan Shock Award from the National Institutes of Health, Ellison Medical Foundation Junior and Senior Scholar Awards, Merck Prize, Genzyme Outstanding Achievement in Biomedical Science Award, Bio-Innovator Award, David Murdock-Dole Lectureship, Fisher Honorary Lectureship, Les Lazarus Lectureship, Australian Medical Research Medal, The Frontiers in Aging and Regeneration Award, Top 100 Australian Innovators, and TIME magazine’s list of the “100 most influential people in the world”. []

David on LinkedIn: David A. Sinclair, Ph.D. A.O.

David on Twitter: @davidasinclair

(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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