Prompt Cast
David Sinclair's Research on Sirtuins, NAD, and Aging
TLDR David Sinclair discusses his research on sirtuins, NAD, and epigenetics of aging, highlighting the potential benefits of activating sirtuins for mimicking calorie restriction and extending lifespan in organisms. His work focuses on the importance of NAD levels in regulating sirtuins and cellular survival, with ongoing exploration of molecules like resveratrol and Terra Stilbin for potential health benefits.
Timestamped Summary
00:00
Professor David Sinclair discusses his research on sirtuins, NAD, and the epigenetics of aging in a detailed and informative conversation with Peter Attia.
06:17
David Sinclair's interest in aging began at a young age, leading him to pursue research in molecular biology and eventually join Lenny Guaranti's lab at MIT to study genes that control aging.
12:29
David Sinclair joined Lenny Guarenti's lab at MIT in the mid-90s, focusing on studying aging genes, particularly the Sir2 gene and its role in gene silencing and longevity.
18:51
SIRT-2 proteins play dual roles in gene silencing and DNA repair, with a focus on coordinating mating and DNA repair processes, and are also involved in targeting proteins beyond histones for controlling signaling and metabolism in cells.
25:06
Research has shown that activating sirtuins, specifically SIRT-2 proteins, can mimic the benefits of calorie restriction and potentially extend lifespan in organisms, highlighting the importance of these genes in responding to biological stress and promoting survival.
31:23
David Sinclair moved to Harvard in 1999 and decided to stay in Boston due to the stimulating environment and opportunities for impactful research, leading to discoveries on the importance of NAD levels in regulating sirtuins and cellular survival.
37:55
NAD levels cannot be easily shuttled between cells, and only NAD plus can activate sirtuins, leading to the discovery that high doses of nicotinamide inhibit sirtuins and the identification of the PNC1 gene that mimics caloric restriction and raises NAD availability.
44:20
Resveratrol extended lifespan in organisms with a defined genetic pathway, showing a clear connection between the molecule and longevity.
50:56
Resveratrol showed lifespan extension in mice when fed every other day, potentially enhancing caloric restriction effects.
57:05
Resveratrol was considered a proof-of-concept molecule, leading to further exploration of synthetic molecules and clinical trials, with some formulations showing potential benefits in humans despite challenges with bioavailability and dosing.
01:03:11
Terra Stilbin, a more novel version of resveratrol with methyl groups, is being explored alongside NAD precursors for potential health benefits.
01:09:32
There is ongoing debate in the field about the transport of NR and NMN into cells, with evidence suggesting that both raise NAD levels effectively in humans.
01:15:37
NAD levels in the ovary and egg may affect aneuploidy, but NAD precursors could potentially improve egg health and fertility.
01:22:04
Gene expression patterns are like analog information that can be disrupted with aging, leading to cells losing their identity and functionality, but there is hope in accessing and restoring this information for potential longevity breakthroughs.
01:28:20
An ideal experiment to accelerate knowledge in longevity research would involve giving a group of 5,000 people certain medicines and monitoring changes in mortality rates over a few years to potentially prove their effectiveness.
01:34:41
Children become aware of mortality around age seven, but often push the thought aside until later in life, as discussed by David Sinclair in a personal conversation.
Categories:
Health & Fitness
