Matt Kaeberlein, Ph.D.: The biology of aging, rapamycin, and other interventions that target the aging process

**Peter Attia** (0:11)
Hey everyone, welcome to The Drive Podcast. I'm your host, Peter Attia. This podcast, my website and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, full stop, and we've assembled a great team of analysts to make this happen. If you enjoy this podcast, we've created a membership program that brings you far more in-depth content if you wanna take your knowledge of the space to the next level. At the end of this episode, I'll explain what those benefits are, or if you wanna learn more now, head over to peterattiamd.com forward slash subscribe.
Now, without further delay, here's today's episode.
My returning guest this week is Matt Kaeberlein. Matt is recognized globally for his research on the basic biology of aging. And Matt is clearly for me on the short list of people who I always reach out to when I have questions about aging. I consider him an amazing mentor and an amazing scientist. Matt was a previous guest way back in episode number 10, circa mid 2018, when we dove deep into his background and his interest in aging and the origins of the Dog Aging Project, which uses rapamycin to study companion dogs. In this episode, we pick up that baton and go even deeper, but we also take an even broader look at aging, arguably the broadest look I've taken in any podcast, because we really start from the nine hallmarks of aging and talk about each of them. And then we tie it into a framework for how do you think about aging? Sort of a top-down view, a disease-centric view, or a bottom-up view through the lens of biology. And we talk about some of the pros and cons of each of these.
We then pivot our discussion to talking about rapamycin. Matt and I both speak very openly about our personal use of rapamycin and all the trials both in animals and humans that have led us to our conclusions.
We then return to The Dog Aging Project where Matt provides an update on some of the exciting work that's being done there and some of the exciting work that's being done elsewhere in his institution with respect to rapamycin trials in humans and what they can be targeting in the short term to better understand the impact of these drugs and drugs like rapamycin, rapalogs, so to speak, how they can impact humans in a long-term way when even though we can't really study humans in a long-term way. We also discuss a relatively new molecule that many of you may not have heard of called Taurin-2, which is like rapamycin, another inhibitor of mTOR, but one that does so via a slightly different mechanism. It looks quite promising. And we discuss what that may or may not imply. And we finish up our discussion with another deep dive into sirtuins, NAD, NR, and NMN, the precursors to NAD. So I think if you have any interest in the topic of aging, you're gonna find this episode probably riveting, if not at least half as riveting as I did, which is still to say very riveting. So without further delay, please enjoy my conversation with Matt Kaeberlein.
Hey, Matt, awesome to have you back on the show. It's been a while because you were one of the first to be on the show. The very, very initial and original guests on this podcast. I've been looking forward to having you back from almost the moment we finished our first discussion.

**Matt Kaeberlein** (3:37)
Yeah, thanks, Peter. It's great to be back.
Unfortunately, we can't see each other in person, but this is the next best thing.

**Peter Attia** (3:44)
Yeah, yeah, I know. We certainly will get together in person soon, I'm sure. There are so many things I wanted to talk about, and I think the last time we spoke, we focused mostly on our mutual favorite drug, rapamycin, and our favorite pathway, the mTOR pathway. And certainly for those listening, I don't want them to think we're not going to touch on that today, we absolutely are. But I wanna start even broader than that, because so often you and I are having these discussions about all things that pertain to aging, and I find you to be one of the most thoughtful people across the topic. So I sort of wanna start with these broader questions about aging.
A lot of people have different definitions of aging, and truthfully, I'm not sure I even know how to define aging sometimes.
It depends, I guess, on the context in which I'm asked. I think if my five-year-old asks me about aging, I would come up with one answer, and if I'm giving a keynote talk and somebody asks me about aging, I'd have to give a different one. So what are some of the ways that you really describe aging?