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

Original release date: 11/5/2018
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.
Show notes page: peterattiamd.c...
About:
The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. With over 10 million episodes downloaded, it features topics including fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more.
Peter is the founder of Attia Medical, PC, a medical practice with offices in San Diego and New York City, focusing on the applied science of longevity. The practice applies nutritional biochemistry, exercise physiology, sleep physiology, techniques to increase distress tolerance, lipidology, pharmacology, and four-system endocrinology to increase lifespan (delaying the onset of chronic disease), while simultaneously improving healthspan (quality of life).
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[@scottk1525]

Yeah I didn't understand a word of this.

[@damarischiquete8084]

Congratulations for the best interview to David Sinclair PhD... shows that the interviewer is well educated in the field to do a deep talking about science.
Thank u so much to both!! You are awesome guys!

[@seabound1350]

I whish Peter wouldnt interupt so much when David is trying to explain things. It takes away so much.

[@thinkandquestion5156]

I look at it as a discussion, conversation, not a strict Q & A session.

[@jellybeanvinkler4878]

I was happy that he did, because it was going over my head til Peter veered David into lay person's understanding.

[@elvay6847]

Typically I am fine with Peter interrupting, as these podcasts are discussions and not lectures. But Peter was particularly annoying in this one. He completely derailed David many times.

[@mixedandmashed]

Two of my favorites. Thanks for this!

[@chrisportislander2458]

"I assure you the listeners are still with us."
YES! I am!

[@rossbarker3362]

I'm confused by this nicotinamide, David was explaining it and you interrupted him and Said "OH!, I get it" I'm glad you get it so U can explain to me, it seems the MNM/NAD excites the Sirtuins and this is a good thing as they can make repairs and do there thing, but the nicotinamide, B3, inhibits the Sirtuins, U said something about a feedback loop, how can both statements be true?

[@allurbase]

there are several chemicals, nicotinamide mononucleotide (NMN), nicotinamide riboside (NR) and nicotinamide (NAM or vitamin B3). NR is converted to NMN and depending on conditions sometimes NMN is converted back to NR. NMN is mainly converted to NAD+ that is what we want, because NAD+ is necesary for the Sirtuins activity. And if I'm not mistaken after using the NAD+ you are left with NAM (aka vitamin B3). When you have too much NAM this Sirtuins activity is inhibited and thats your negative feedback, convert NAD+ to NAM until there is too much NAM.

[@NavidNathoo]

This might be bias, but here's an overview of the NMN vs NR and why Elysium uses NR. TL;DR = NMN is bigger, NR is smaller = NR [likely] has better cell absorption rates but hasn't been tested side by side yet. --> www.elysiumhealth.com/en-us/knowledge/science-101/nmn-and-nr-how-these-nad-precursors-measure-up

[@filipporivalta]

thanks from Italy for sharing precious information in this practical way... it's part of my graduation thesis.

[@stefanlucchesi7789]

Si puo davere mettere indietro il tempo biologicamente di una persona o e' una cosa solo delle industrie farmaceutiche

[@filipporivalta]

stefan lucchesi andare contro natura non si può. Accompagnare al meglio un percorso biologico è possibile, la parole d’ordine però è rispetto e totalità di azione... movimento, alimentazione, riposo. Yin e Yang è la regola. Quando si va oltre succede il danno, sul breve o sul lungo. Peter Attia è un medico che da molta importanza alla sfera mentale e fisica anche

[@lizaalexeeva7009]

I want peter attia merch

[@salardz]

Great, great video. Very interesting points were coverd.

[@kanahn7402]

I didn't get the bit about the synergy between alternate day fasting and resveratrol. Where they saying it's better to skip the resveratrol when fasting. Or was the resveratrol the same on fasting and feeding days?

[@LilianaGrueber]

Both of you guys are AMAZING!!!!! I love it! Super interesting and useful! Way to go Peter Attia!

[@edisonclaro5363]

hi I follow your work and it is really amazing.David told us what he takes. and what about you .
Do you take NMN or other like that?

[@leonardodamico9344]

Could you do a video on parkinson disease

[@SquatFull]

I would appreciate a response to Dr. Charles Brenner's
Article "Sirtuins are not conserved longevity genes"
Life Metabolism, Volume 1, Issue 2, October 2022, Pages 122-133.

[@FatherGorgony]

Thank you, Peter for your English. It would be nice if you translate😂 or just repeat what David says in Australian.

[@rui-9-cs315]

💕

[@sciencekid]

More people need to listen to this!

[@cholakicha]

59:00

[@janelopez5988]

The overjoyed himalayan intrinsically hate because maid utrastructurally admire across a wide-eyed word. soggy, cheerful wave