David A. Sinclair, Ph.D., A.O. is a Professor in the Department of Genetics at Harvard Medical School. He is best known for his work on understanding why we age and how to slow its effects. His research has been primarily focused on the sirtuins, protein-modifying enzymes that respond to changing NAD+ levels and to caloric restriction (CR) with associated interests in chromatin, energy metabolism, mitochondria, learning and memory, neurodegeneration, and cancer. The Sinclair lab was the first one to identify a role for NAD+ biosynthesis in regulation of lifespan and first showed that sirtuins are involved in CR in mammals. They first identified small molecules that activate SIRT1 such as resveratrol and studied how they improve metabolic function using a combination of genetic, enzymological, biophysical and pharmacological approaches. They recently showed that natural and synthetic activators require SIRT1 to mediate the in vivo effects in muscle and identified a structured activation domain. They demonstrated that miscommunication between the mitochondrial and nuclear genomes is a cause of age-related physiological decline and that relocalization of chromatin factors in response to DNA breaks may be a cause of aging.

Time stamps:

9:35 Start of podcast.

10:53 Does when you eat matter more than what you eat?

12:48 Time restricted feeding and longevity.

17:04 What causes us to age?

20:05 What cellular information is being lost?

26:35 What Causes DNA break?

28:47 DNA breaks as clastogenesis.

29:32 Food and DNA breaks

31:28 PARP enzymes.

34:57 NAD

40:15 NAMPT

42:35 Nicotinamide and sirtuins.

44:25 Methylation and methyl groups.

45:44 Sirtuins.

48:11 Heat/cold and sirtuins/NAMPT

52:54 What do sirtuins do with ADP ribose.

56:15 Role of active sirtuins.

58:25 Other longevity genes.

1:04:30 Importance of mitochondrial NAD levels.

1:05:50 Ketosis and NAD.

1:11:20 Resveratrol.

1:14:45 Xenohormesis and plant molecules- my view vs David’s

1:19:55 Resveratrol trials, concerns about resveratrol.

1:26:05 mTOR

1:31:37 David's plant based diet- and why it could be better

1:38:10 Meat consumption and the environment

1:45:35 Where to find David's stuff.

1:47:20 The most radical thing David has done recently.

David’s contact info:

https://genetics.med.harvard.edu/sinclai

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