Vamsi Mootha, M.D.: Aging, type 2 diabetes, cancer, Alzheimer's disease, and Parkinson's disease – do all roads lead to mitochondria?

**Peter Attia** (0:04)
Hey, everyone, welcome to The Peter Attia Drive. I'm your host, Peter Attia.
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.
Hey everybody, welcome to this week's episode of The Drive. I'd like to take a couple of minutes to talk about why we don't run ads on this podcast, and why instead we've chosen to rely entirely on listener support. If you're listening to this, you probably already know, but the two things I care most about professionally are how to live longer and how to live better.
I have a complete fascination and obsession with this topic. I practice it professionally, and I've seen firsthand how access to information is basically all people need to make better decisions and improve the quality of their lives.
Curating and sharing this knowledge is not easy, and even before starting the podcast, that became clear to me. The sheer volume of material published in this space is overwhelming. I'm fortunate to have a great team that helps me continue learning and sharing this information with you. To take one example, our show notes are in a league of their own. In fact, we now have a full-time person that is dedicated to producing those, and the feedback has mirrored this. So, all of this raises a natural question. How will we continue to fund the work necessary to support this?
As you probably know, the tried and true way to do this is to sell ads, but after a lot of contemplation, that model just doesn't feel right to me for a few reasons. Now, the first and most important of these is trust. I'm not sure how you can trust me if I'm telling you about something when you know I'm being paid by the company that makes it to tell you about it.
Another reason selling ads doesn't feel right to me is because I just know myself. I have a really hard time advocating for something that I'm not absolutely nuts for. So if I don't feel that way about something, I don't know how I can talk about it enthusiastically. So instead of selling ads, I've chosen to do what a handful of others have proved can work over time, and that is to create a subscriber support model for my audience.
This keeps my relationship with you both simple and honest.
If you value what I'm doing, you can become a member and support us at whatever level works for you. In exchange, you'll get the benefits above and beyond what's available for free. It's that simple. It's my goal to ensure that no matter what level you choose to support us at, you will get back more than you give.
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Again, the podcast will remain free to all, but my hope is that many of you will find enough value in, one, the podcast itself, and two, the additional content exclusive for members to support us at a level that makes sense for you. I want to thank you for taking a moment to listen to this. If you learn from and find value in the content I produce, please consider supporting us directly by signing up for a monthly subscription. My guest this week is Dr. Vamsi Mootha. Vamsi is a professor of systems biology at the Harvard Medical School. He has an appointment at The Broad Institute, which is actually where we met to conduct this interview. And we talk a little bit about what makes The Broad so special. He specializes in rare mitochondrial diseases, as opposed to longevity per se, something that I love to talk about. But I think you'll see in this interview why it's so interesting to talk to someone who specializes in rare orphan mitochondrial diseases about longevity. His laboratory uses a blend of genomics, computational biology, biochemical physiology, and systems biology to study mitochondrial function and dysfunction. He received his bachelor's in mathematics and computer science at Stanford before going on to Harvard as part of the joint MIT Harvard program in medical school. He stayed in Boston to do his training in internal medicine, though as we discuss, he now focuses exclusively on research. He's received more honors and awards than I could name here, but it's always worth mentioning it when someone is a genius award recipient. So he won the MacArthur Foundation Award in 2004, which obviously puts him in pretty rarefied earth. In this episode, we talk about a lot of things. We start with, at least for me, one of the best discussions I've ever had on the mitochondria. And you might think at first that some of this recapitulates things that were discussed on previous podcasts. You may recall we had a great discussion on the mitochondria with Navdeep Chandel, but we go a little bit deeper and we talk more about some of the evolutionary pressure around the mitochondria. And even though at first you might think, well, gosh, this seems awfully scientific. Where's the application? If you stick with it, you're going to see where it comes and how understanding these rare orphan diseases that most of us have never heard of can give us an insight into aging. We do eventually start to talk about metformin, which I know many people ask about. And he provides a great insight into, or several great insights into what metformin may or may not be doing. And again, at least for me, this was like just the master's class in mitochondrial biogenesis, electron transport chain, et cetera. Talk about ways that we can target mitochondrial proteins and complexes to treat disease. But perhaps the single most insightful and interesting thing that we talked about that completely blew my mind was the role of hypoxia as a treatment. I wanna repeat that again. The role of hypoxia, oxygen deprivation as treatment. Now, we're gonna cover this in a way that I think is very interesting. So, I don't wanna say any more about it. But I do want to add a disclaimer to this that Vamsi and I spoke about after the podcast, and I wanna make sure it's here, right? So, Vamsi emphasizes that their published research to date on the beneficial effects of hypoxia in animal models of mitochondrial disease is still in its early stages, and it's restricted to animal studies. It is not yet ready to be applied to humans.