How metabolic and immune system dysfunction drive the aging process, the role of NAD, promising interventions, aging clocks, and more | Eric Verdin, M.D.

**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, and we've established a great team of analysts to make this happen. It is extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members, and in return, we offer exclusive member-only content and benefits above and beyond what is available for free. If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription. If you want to learn more about the benefits of our premium membership, head over to peterattiamd.com/subscribe. My guest this week is Dr. Eric Verdin. Eric Verdin is a physician scientist who spent two decades uncovering how epigenetics, metabolism and the immune system drive aging and now serves as the president and CEO of the Buck Institute for Research on Aging. In this episode, we discuss Eric's path from studying viruses and HDACs to leading the Buck Institute and focusing on aging research. How aging changes the immune and nervous system, thymus shrinkage, for example, loss of T cell, diversity, chronic inflammation and weaker vaccine response and why these changes can ultimately shorten lifespan, metabolic drivers of aging, oxidative stress, fuel choice, insulin and IGF-1 signaling, and practical tips on zone 2 cardio, ketogenic nutrition and GLP-1 drugs. Why NAD levels fall with age, the role of sirtuins and CD38, what NMN, NR, IV, NAD can and can't do, and the importance of stopping NAD loss. Drugs that have the potential to slow aging, including optimal rapamycin dosing, growth hormone-based thymus regrowth, blocking IL-11 or IL-1, and how these things might compare with, say, exercise. Current ways to measure biologic age and the limits of today's epigenetic clocks, new proteomic and organ-specific tests, and how combining multiple metrics with wearables may guide personalized longevity care. So, without further delay, I hope you enjoy my conversation with Dr. Eric Verdin.
Eric, thank you so much for coming to Austin. I know it wasn't just to talk to me. I know that half of it was getting you to drive on the track at COTA tomorrow with me, so we're going to have some fun there.

**Eric Verdin** (2:54)
My pleasure.

**Peter Attia** (2:55)
But as much as I think the two of us could sit here and talk about race cars for the next three hours, I don't think the audience would appreciate it or care for it as much as they will care for what we will talk about, which is your work in Geoscience. So maybe give folks a little bit of a sense of what attracted you to this field and how your journey and background brought you where you are.

**Eric Verdin** (3:17)
It's a bit of a serendipitous type of story in the way that I'm an MD by training from Belgium, did my last year of medical school at Harvard, and this just sort of opened my eyes to a whole world. I was the first person in my family to go to college, ending up at Harvard with some of the best teachers, some of the best students was just mind-blowing, and I went to medical school wanting to do research. Never had that sort of a doctor fiber, and I call it, so really wanted to research. And so after this, finished medical school and came back for directly a post-doc at the Jocelyn Clinic working on diabetes and metabolism. So this is where the story gets circuitous. Ended up becoming interested in the reason for the etiology of type 1 diabetes, and worked on viruses and autoimmunity. This eventually led me to mostly a career in virology, which confuses people. So I spent many years working on a variety of viruses, including HIV and herpes viruses and so on. And through that work, we ended up cloning a family of protein called some of the first epigenetic regulators, the HDACs.
And the HDACs, at the time, there was 1996, we were responsible for the cloning of a whole family of these epigenetic regulators, ended up being important in aging. And starting in around 1995, 1996, my lab slowly shifted towards the study of aging. And to this point today, actually, I only have one last postdoc in the lab who's working on HIV. The whole lab is actually focused on epigenetics, immunology and metabolism, so that the interface between these variables. So in some ways, it's the beauty of an academic career, which I've just followed my interests, sometimes followed the money a little bit in terms of funding. Now, I mean, I have another additional responsibility, which is to lead the Buck Institute for Research on Aging. I've split my time between the lab and some more leadership type of activities.