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

**Peter Attia** (0:04)
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The drive is a result of my hunger for optimizing performance, health, longevity, critical thinking, along with a few other obsessions along the way. I've spent the last several years working with some of the most successful top-performing individuals in the world. And this podcast is my attempt to synthesize what I've learned along the way to help you live a higher quality, more fulfilling life. If you enjoy this podcast, you can find more information on today's episode and other topics at peterattiamd.com.
Hi, everyone. Welcome to this week's edition of The Peter Attia Drive. I'm Peter Attia. This week, my guest is Professor David Sinclair. He's a professor in the Department of Genetics at Harvard Medical School, and he is the co-director of the Paul F. Glenn Center for the Biological Mechanisms of Aging.
David hails from Australia. That'll take you about 10 seconds into our interview to figure out. He did his PhD in molecular genetics at the University of New South Wales in Sydney.
It was at that time that he met the man that would go on to become his mentor. We talk a lot about him, and this is a guy, Lenny, who's actually come up on other podcasts, so I won't get into him now. But nevertheless, David met Lenny and decided he wanted to come to MIT to study with him, which is what he did. David has gone on to become one of the pioneers in a particular field of aging that focuses on a class of molecules known as sirtuins. I'm sure many of you have heard of sirtuins, but you might not entirely be clear on what sirtuins are. I won't obviously make any attempt to do that here in the intro because we spend so much time talking about that during this episode. The other thing that David is really quite famous for is his role in the discovery of a molecule or class of molecules that stimulate sirtuins, and by the time you get through this episode, you will understand why that may be a desirable thing to do. And among these, the most famous is one called resveratrol. Of course, resveratrol came to fame probably a little over a decade ago when it was noted at least in one study in one type of animal model to promote a longevity phenotype. And of course, what really made it interesting, at least for the lay press, was that resveratrol is found in very low concentrations in the skin of grapes. And therefore the logic went, hey, grapes make wine, wine contains resveratrol, wine makes you live longer. Hallelujah, the French paradox has been resolved.
Slight spoiler alert, that's not true, but we get into the whys that might be the case.
This episode, we only had, when I say only, meaning we had less than two hours, but like has happened in other podcasts, including the one with Rhonda Patrick, after we closed the podcast, because I wanted to be respectful of David's time, he had to catch a flight to New York right after we spoke. This interview took place in Boston.
We ended up talking for another 15 minutes, and unfortunately, that 15 minutes was some of the most intense, detailed, nuanced discussions of it, and I left thinking, gosh, I wish we had more time to talk. So I suspect David and I will speak again. David has a book coming out next year, and I think that'll provide another great opportunity to sit back down with him. In this episode, we talk a lot about his postdoc at MIT. He came out of a powerhouse lab that has produced other notable folks, including folks we've already interviewed, like Matt Caberlin and folks we've talked about, like Brian Kennedy. We talk about his contribution to the understanding of sirtuins, which was something that was coming out of Lenny's lab, and David really picked that up and ran with it. What are these things? What do they do? What's their role in aging, DNA repair, gene silencing? We go over all this stuff in detail. We talk a lot about NAD and its precursors, specifically something called NMN. So if you are listening to this and you are in the camp of trying to understand how to make heads or tails of NAD, NR, NMN, I think this episode will be helpful. Tragically, it was not until 24 hours after we did this episode that I ran into George Vlasek on an airplane who mentioned to me a paper by Josh Rabinowitz in cell metabolism that came out about a month before we did this interview that we will link to that I think makes a very compelling case for the futility of orally administered versions of these precursors. And that would have been a really interesting discussion to have with David because of his expertise in this. So at some point I'll probably want to interview Josh and we'll go into that in really detail because again, unless you've been up in the Himalayas hunting yeti, you're probably aware that these are kind of the hottest supplements out there. We talk a lot about NAD levels. What do these things mean? Where does it go? Where is it produced? We again, as I alluded to above, talk about resveratrol and its potential in life extension. When we talk about the connection then between sirtuins and NAD, we talk about his rationale for what he does. So David is actually very open about, you know, kind of the stuff that he does personally, including the fact that he takes resveratrol and metformin and NMN himself. We also go into the differences between some of these molecules and again, allude a little bit to his book.