Centenarians, metformin, and longevity | Nir Barzilai, M.D.

**Peter Attia** (0:11)
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Now, without further delay, here's today's episode.
My guest this week is Nir Barzilai. Nir is making his third appearance on the podcast, the previous one being in August 2020 with Joan Manek, and then originally back in January of 2019 In this episode, Nir and I speak mainly about two topics, just in much, much more detail than we've ever spoken about them before, at least publicly, centenarians and metformin. We start the conversation speaking about centenarians with a focus on what can the majority of us who are not centenarians learn from them. Talk about longevity genes, such as GH, IGF-1, CTEP, FOXO, TSHR, and APOE. We talk about whether or not environment matters at all in these individuals or whether it's all genetic. Talk about what we can learn about them from the importance of preventing diseases, and we talk about what we can learn from centenarians around extending lifespan while also trying to improve healthspan. From there, we get into a deep dive on Metformin. We talk about the TAME trial now. This is something that we did speak about briefly in our first podcast, but we get into much more detail, and I actually found myself learning some details of the study design that I didn't understand previously.
Talk about Nir's thoughts on why the Rich Miller ITP program found Metformin to be unsuccessful in that model and why he thinks that may or may not apply to humans. We talk about the impact Metformin can have on exercise, both strength training and cardiovascular training. Lastly, we speak a little bit about epigenetic clocks and end with a conversation around NAD precursors. As a reminder, Nir is a director of the Institute for Aging Research at Albert Einstein College of Medicine, spearheading the Longevity Genes Project, conducting genetic research on more than 500 healthy elderly people between the age of 95 and 112 and on their offspring. He is also the director of the Paul F. Glenn Center for the Biology of Human Aging Research and of the National Institutes of Health, Nathan Shock Centers for Excellence in the Basic Biology of Aging. So without further delay, please enjoy my conversation with Dr. Nir Barzilai.
Hey Nir, it's great to have you back. I was thinking about this when I was preparing for the podcast today. There's so much I want to cover that I don't think it's actually going to be possible. I'm pretty sure that we're going to talk as much as we talk today, and I'm going to be saying to the team, all right, let's talk about when we're going to have Nir back because there's really just too many things I want to go through. So anyway, thank you for making time and let's just get right into it.

**Nir Barzilai** (3:20)
Thanks, Peter. I'm happy to come back, but it's you who's coming to me every week and I'm so grateful for what you're doing for this field and for helping all of us catching this field of longevity that's going to come true very rapidly, I hope.

**Peter Attia** (3:36)
Well, I was thinking about the first place I wanted to start and there's really no good one place to start because there's just so much I want to talk about, but let's start with centenarians.
You, along with Dr. Pearls, are probably two of the people who have spent the most time studying this very, very unique subset of the population. So I think everybody knows what a centenarian is, someone who lives to be 100 or more, but there's so much nuance about what it is about these special people. And then there's sort of the pop culture view of this, which is people love to talk about all of the bad behaviors that centenarians engage in, how much more they smoke, how much less they exercise, how much whiskey they drink and all of those things, which are really cute. But when you study them scientifically, and when you study their offspring scientifically, as you've both done, we learn a lot of things.