Rapamycin: potential longevity benefits, surge in popularity, unanswered questions, and more | David Sabatini, M.D., Ph.D. and Matt Kaeberlein, Ph.D.

**Peter Attia, MD** (0:11)
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My guests this week are David Sabatini and Matt Kaeberlein. Matt has been a former guest on three occasions, episode 222 and 175 and all the way back to episode 10, while David was on the podcast way back in episode number nine. Not only are they two of the original guests on the podcast from our 12 part pilot experiment in the summer of 2018, they are also two of the most knowledgeable people on this planet on the topic of conversation today. Rappamycin and mTOR.
In my conversation with Matt and David, we cover the discovery of Rappamycin. We look at how mTOR, which sits at the epicenter of our existence, works and does its job. We talk about the pathways of Rappamycin that are believed to drive its impact and improvement on lifespan. We discuss the initial studies that showed Rappamycin may be zero protective and also what studies have come out since or are currently in progress, which provide more information and clarity around this very important question. Finally, we discuss what is known and unknown about the potential frequency and dosing of Rappamycin in humans. I'm very excited to release this podcast because I don't think there is a question I get asked more about from my patients than this topic. Understandably, because my patients know that I take Rappamycin and have been doing so for about five years, it's understandable that they want to understand if it's something they should be doing too. And I think you'll see from this discussion why I have reservations about just blindly putting people on Rappamycin. In other words, why is our practice not a Rappamycin mill?
I hope that this podcast is helpful, not just for my patients, but everybody listening, including everyone who is interested, of course, in this question. So without further delay, please enjoy my conversation with David Sabatini and Matt Kaeberlein.
Well, guys, we're gonna try something a little different today, which is we're gonna try to have a three-way discussion, which is something we would easily be doing if we were sitting over a meal, but always makes for a slightly more challenging podcast. That said, given our familiarity with each other and your familiarity with this topic, I am 100% confident this is gonna be an amazing episode. It's also an episode that is long overdue. So you guys are both in the camp of, I believe, first dozen or so podcasts that were released on the drive a little over five years ago. Matt, you and I have spoken a number of times since. David, you and I, at least on the podcast have not, obviously in person all the time. So with all that said, many people are gonna be new to this topic. They will have heard a lot about it. They may have even read a chapter about it in my book, which you guys were both very gracious to help me fact check and edit. But here we are. We're gonna pretend that someone coming into this discussion doesn't really know anything about rapamycin, doesn't really know what this mTOR thing is. I hope that by the end of this discussion, we will have provided people with arguably the most comprehensive, quasi concise explanation of all you need to know about said topics.
With that said, I would like to ask each of you to do something I don't often ask my guests to do, which is toot your own horns a little bit about what it is that allows me to say you are each among the two most knowledgeable people on this topic. Let's start with you, David. You've worked on this molecule, rapamycin, your entire scientific career, going back to your PhD. And here we are 30 plus years later, you're still the leading authority on it. Can you tell us a little bit about that?