The Peter Attia Drive
#333 ‒ Longevity roundtable — the science of aging, geroprotective molecules, lifestyle interventions, challenges in research, and more | Steven Austad, Matt Kaeberlein, Richard Miller
Mon, 27 Jan 2025
View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter In this special episode of The Drive, Peter introduces a brand-new roundtable format. Joined by three renowned experts in longevity science—Steven Austad, Richard Miller, and Matt Kaeberlein—the group explores the rapidly evolving field of geroscience. Together, they dive deep into topics like the relationship between healthspan and lifespan, evaluating interventions like rapamycin and senolytics, the role of epigenetic changes in aging, and whether GLP-1 receptor agonists hold geroprotective potential. They also tackle major challenges in funding and public acceptance of longevity research including how geroprotective interventions might be tested in humans. Packed with nuanced debate, humor, and groundbreaking insights, this episode is a must-listen for anyone fascinated by the science of aging. We discuss: The recent rise in public interest in longevity, misconceptions, and the link between healthspan and lifespan [3:45]; Redefining healthspan, the US healthcare paradox, and separating longevity science from commercial hype [12:30]; The need to redirect medical research from disease-specific models to aging-focused approaches [21:30]; Proactive healthcare: rethinking health, disease, and the role of aging [30:00]; Biologic age versus chronologic age, and the limitations and potential of epigenetic clocks [35:00]; The utility and drawbacks of the “hallmarks of aging” as a framework for research and funding [49:30]; The role of epigenetic changes in aging and the challenges of proving causality [56:45]; The translational challenges of moving aging research from preclinical studies to human applications [1:03:45]; Distinguishing between a biomarker of aging and aging rate indicators [1:17:15]; The difficulties of translating longevity research in mice to humans, and the difficulties of testing interventions in humans [1:21:15]; Exercise, aging, and healthspan: does exercise slow aging? [1:35:45]; Are GLP-1 receptor agonists geroprotective beyond caloric restriction effects? [1:41:00]; The role of senescent cells in aging, challenges with reproducibility in studies, and differing views on the value of current research approaches [1:46:15]; How funding challenges and leadership in NIH and other institutes impact the advancement of aging-related research [2:00:15]; Metformin: geroprotective potential, mechanisms, and unanswered questions [2:02:30]; Canagliflozin and rapamycin as geroprotective molecules: mechanisms, dosing strategies, and longevity potential [2:10:45]; Resveratrol and NAD precursors—a lack of evidence for anti-aging effects [2:22:45]; The potential of parabiosis and plasmapheresis to slow aging, the challenges in translating mouse studies to humans, and possible design for human studies [2:29:45]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube
Chapter 1: What is longevity science?
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.
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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 a subscription. If you want to learn more about the benefits of our premium membership, head over to peteratiamd.com forward slash subscribe. Welcome to a special episode of The Drive. Today, we're introducing a new format to the podcast.
It's our inaugural roundtable conversation. For this one, we have gathered three brilliant minds, all former guests of the podcast, to sit down and have a nuanced, funny, sometimes a little heated discussion about one of the most fascinating and rapidly evolving areas of medicine today. also known, I guess, as longevity science. So joining me for this episode are Drs.
Steve Ostead, an expert in aging biology and author of groundbreaking research on extending healthspan, Richard Miller, pioneer of the study of anti-aging interventions through the Interventions Testing Program, or ITP, which you hear me reference a lot, and Matt Kaberlin, whose expertise explores the intersection of genetics, aging, and translational research.
And Matt, of course, is famous for his work in the Dog Aging Project. So in today's roundtable, we discuss a number of things, such as the relationship between healthspan and lifespan. And what does healthspan actually mean? Is it something we should try to define? Can you improve one without improving the other?
What has caused a surge in the public interest in longevity science and what major barriers are preventing longevity research from reaching its full potential? This actually was one of my favorite parts of the discussion. How do we evaluate the effectiveness of interventions like rapamycin, senolytics, or calorie restriction in humans, where it's very difficult to study them for obvious reasons?
Are there reliable biomarkers or aging rate indicators that can measure biologic aging, which of course is a very hot topic? What role do epigenetic changes play in aging? Specifically, are they causal? Are senescent cells a valid target for longevity interventions, or has their role in aging been overstated?
Are GLP-1 receptor agonists, for example, drugs like terzepatide and semaglutide, potentially geroprotective beyond just their weight loss effects? How do we overcome the funding and political challenges that prioritize disease-specific research over foundational aging science? What would it take to make longevity research more mainstream and gain broader support from the public and policymakers?
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Chapter 2: How does healthspan relate to lifespan?
It's a surprise to me that longevity has become so big because for a long time, we tried to move away from that in the aging field because we were worried that people were thinking of longevity as, well, we're going to keep frail, feeble, old people alive longer. That's what longevity meant. When really what we were trying to do is extend health.
So I'm kind of surprised, but I think it's because there are certain people of a certain age who've started to think about their own longevity. And then I think there's a whole new generation of tech entrepreneurs that really feel like this is a problem that will allow them to live healthily for several decades, at least longer than they are now. So I think it's a combination.
It's a multi-generational thing. That kind of surprises me. And you haven't seen this before, to be clear.
So 30 years ago, you didn't see glimmers of this?
No, 30 years ago, I would have said, let's not even say the word longevity. Let's say healthspan. But that's changed quite clearly as more and more people have been from the outside. They're sort of peeking in at the field. I don't think the people in the field itself have changed the way they talk that much, but the people eavesdropping on the field certainly have. Rich, is that your experience?
Yeah.
Well, I think there are two aspects that I would want to emphasize in response both to your question and to what Steve said. In response to the question, I think people have always been fascinated for millennia on things they could do to stay alive and healthy as long as possible. But there were actually scientific discoveries in the 90s that showed that it could be done.
And then in the last 20 years, there's evidence that it can be done, at least in mice, with pills. So that naturally should lead to speculation that there could be pills you could give to people that would postpone poor health for a substantial amount of time. 20 to 30% is what we're seeing in mice, and 20 to 30% would be very important for people. So I think that is a part of it.
The other part is that there are now people who are making a lot of money by selling stuff that is untested to be polite about it or is useless to be less polite about it to gullible customers. And so people who want to make a lot of money have finally found that there's an impetus
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Chapter 3: What are the barriers to longevity research?
Let me answer your question first. Why the lag? I think there's a whole batch of reasons, and they're important, and they're easy to spell out. One is the prevailing attitude is that aging is there. There's nothing you can do about it. I'm going to not be able to outwit aging, though I may be able to be maybe healthier in my older years.
The notion that aging is not malleable, though wrong and provably wrong, is still the overwhelming opinion even of reasonably educated scientists and certainly of the lay public. Then commercially, there are companies that make a ton of money selling stuff that doesn't work by pretending with a wink and a nod and a lawyer that it might slow the aging process down.
And since they can make a lot of money, they don't actually have to spend valuable marketing dollars on doing research and stuff to prove that it works. Some of the drugs that at least in the hands of our mouse group, the ITP interventions testing program, some of the drugs are the patent is owned by another company or they're out of patent or it's a natural product.
None of that says take me to whoever owns a big pharmaceutical firm. And also, even if you do it right and you really want to do it and you've got a very large budget, it's not an overnight kind of thing. Any one drug, a leading agent that, like rapamycin, which you mentioned, and the half a dozen others that we've shown work, at least in mice,
finding something in that same family that works really well, that is safe for people, that's the member of the 20 congeners of that drug that's best and most potent and safest, that's not at all trivial. That takes a long time and it takes a commitment of money and time and effort and intellectual resources. We're at the place where we can start to make an argument that that's a good idea
but make a good argument that that's a good idea to people who actually have the resources to carry it out has not so far been enormously successful, unfortunately.
Can I push back a little on what Rich said about healthspan versus lifespan? Several papers have come out recently showing that the gap between healthspan and lifespan in people is actually increasing, and it's increasing the fastest in the United States, and it's increasing faster among women than men. So in humans, this is a very real gap and it's a growing gap.
And I think one of the advantages of the kind of geroscience, the stuff that we do, is that Richard's right. We don't see this in our experimental systems. So this, to me, emphasizes the fact that we need to change the focus. I think one of the reasons that the gap exists is we're getting better and better and better.
at treating heart disease and cancer and all these things and keeping people alive when they wouldn't have been alive 10 years ago. But this is a really important factor, I think, about thinking of public health globally.
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Chapter 4: What role do biomarkers play in aging research?
So the situation is even in the United States where life expectancy is relatively short compared to other nations, a big chunk of that life expectancy is not spent in good health. And it's exactly for this reason.
But there are two different issues that are being confused here in the discussion. One is the issue of whether you can help middle-aged people live longer. And everybody's agreed that we're getting better at that. We're pretty good at it. And that certainly contributes to whatever you think healthspan might mean.
That's an issue, however, that is quite different from a concoction that slows aging do so by extending healthspan. Those both have the word healthspan in them. but they're different and shouldn't ever be confused with one another. The other point in this question you asked was what is healthspan? My own personal answer to that is it's a useless term. That is because no one can define it.
It's not because no one is smart. It's because the term itself is vacuous and nebulous. If you have somebody that gets a certain chronic disease here and then another one, and then they fall down and bump their head, and by the way, they go to the hospital with COVID, etc., etc.,
defining when in that 20 to 30-year period they flicked the switch, now they have gotten to the end of the healthspan is impossible and of no interest. The general notion that people are interested in is whether you can do stuff to keep people healthy for a long time, either without changing their life expectancy or by changing their life with changing their life expectancy.
Those are interesting. But you don't have to assign a number, a healthspan digit.
I don't like the medical definition of healthspan, which I believe is, quote, the period of time in which an individual is free of disability and disease. I find that to be a very unhelpful definition. It's awful, yeah. But part of the reason it's awful is it's binary. Yeah, exactly. But if we made it analog instead of digital, I'm not saying that makes it easy. It's still very challenging.
But now it allows us to start talking about things.
Except it's a concept. It's a qualitative concept. I think we should try to make it to where we can't actually come up with a way to measure whether we call it healthspan or not. That doesn't really matter. I kind of agree with Rich. Like, I agree with what you're saying, except I think it's a really useful term as a concept.
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Chapter 5: Can exercise slow aging?
I mean, I just think that's the pace that science moves and the rate at which these concepts can sort of permeate the public sphere. So it's frustrating in a sense that it's moved so slowly. I also wonder, because you sort of said, are we at a longevity bubble? I don't know.
I think maybe we're still kind of in the early days of this hockey stick moment where you're getting this exponential increase in attention. My hope is As we go forward, it will become more scientific and less snake oily. And it's a spectrum. There's this huge gray area in the field right now of what's real and what's not real.
And I think none of us at this table actually can really define exactly where in that gray area that line is or is there a line.
To that point, Matt, what is the collective wisdom of the group on the funding appetite for that? Because I agree with you completely. Like if we could channel this exuberance away from kind of the highly commercial speculative grifting towards the budget increasing legitimate investigative, that would be awesome. What is the appetite right now of NIA with respect to this?
I think it's hard to say it. And I mean, NIH is a moving target. And as we all know, there's going to be a lot of change coming in the near future. So cautiously optimistic, I would say if you look historically, it's been really pretty terrible. The percent of NIH budget that goes to biology of aging, I think is still probably around half of 1%.
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Chapter 6: Are GLP-1 receptor agonists geroprotective?
Sorry, just to put numbers in perspective, NIA gets what percent of NIH?
Not NIA. No, no, I understand. Within NIA, there's a sub fraction that goes to biology of aging, right? Yes, yes, yes. Yeah.
But I'm saying there are 17 groups of NIH. NIA being one of them gets what fraction of NIH budget, roughly? I think it's roughly 3%. 3% of NIH budget is NIA. Within NIA, how much goes to this type of research?
It was about $350 million a few years ago. It might be a little higher than that, but I don't think it's ticked up any more proportional to the increase in NIH budget since then. So it reaches about half of 1%. Wow.
What's your level of optimism, Rich? You're obviously very close to this.
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Chapter 7: What challenges exist in translating research to humans?
that NIH will wake up and start to pay attention to aging research the way they should. It's near zero. It's been near zero for 30 years now.
Even with this outside attention?
Well, it's gone up. I mean, they funded the ITP, the Interventionist Testing Program, 20 years ago, and they liked it, and they doubled our budget about 15 years ago. So that's something, and I'm very, very grateful to them for that. But there's still an enormous untapped potential for making progress in the basic biology of aging. And the reason is, again, a matter of defending TERF.
If you are a cardiologist researcher or an oncologist researcher or an AIDS researcher or an Alzheimer's researcher, anytime somebody says the smart play is to reduce your budget by 10% or your institute's budget by 10%, we're going to go there faster if we spend money on aging and its relationship to the disease you care about. You get the porcupine defense.
You don't take any of my money because Alzheimer's is important. Little kids with leukemia are important. Breast cancer is important. You go away. And that is the predominant feeling. Most of the people making those decisions were not trained in aging research. They view it as something interesting. I read something about that in Time Magazine the other day.
But they don't understand that to actually conquer or slow down or affect aging, or protect against the disease they care about, the smart play is to do aging research. And so they view your suggestion, which I, of course, agree with 100%, as an imposition, an invasion to be repelled at any cost. No one in a position of power has had whatever it takes to reverse that.
And if he or she tried to do that, Congress would, even a good Congress, would smack them down. The Alzheimer's Group has 100 lobbyists. The cancer group has 100 lobbyists. The AIDS group has 100 lobbyists. The aging group has two lobbyists, one who's a lawyer and one who takes the calls. And it's not enough to do it. Can I just add something real quick?
I agree completely. And I think as well, the reputation of the field has hindered that transition as well. So historically, the field was viewed as not very mechanistic, kind of phenomenological, became much more mechanistic starting around the time of Cynthia Kenyon's work and since then, but has continued to have a reputation problem as not being as rigorous as other areas of research.
So I think it is absolutely a turf war. And there's this overcoming the reputational problem, which makes it harder for scientists serious people in funding and policy circles to give it the attention it deserves, in my opinion.
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Chapter 8: How does funding impact aging research?
I would. And I mean, the reality is the research flows from where the dollars are going. This has been seen over and over and over at NIH. You shift resource allocation to a certain area and the scientists will follow and they will submit grants. to get grants in the place where the funding line is the highest.
So if somebody came along and said, we're going to go from 0.5% to 50% of NIH budget is going to go to biology of aging, you'd have no shortage of people. I mean, it'd be kind of messy at first, but you'd have no shortage of people applying for grants and becoming experts in the biology of aging.
And the system would work. You'd get the best and the brightest that would go into that and do that. So this then begs another question that is a tired question, but I can't help but ask it at this point. Is aging a disease?
Is that even a relevant question? Call me, call me, call me, call me. Yes, Mr. Miller. It's important to use words optimally and to distinguish causes from effects. One of the bad things about aging is it's a risk factor for many diseases. Some things, other risk factors for diseases, aging is a risk factor for disease. And so saying that aging is a disease confuses that discussion.
It makes it impossible to see that relationship. So calling aging a disease is a fundamental error. The question itself is incorrect.
I agree completely. I think it's the wrong question.
I agree, but I think we have that idea for marketing purposes, not for scientific purposes. And the idea is, well, the money goes to diseases. Let's call aging a disease, because I think what we're trying to do is we're trying to treat aging as if it were a disease, even though I would agree with both of you. I don't think it's a disease.
I think that destroys the word disease if we include aging in it. But I think there was a reason that suddenly this came because you thought, oh, maybe this will get Congress to pay attention.
You're right. It's a marketing ploy. And if you think you can convince people of the importance of aging research only by crossing your fingers and saying, oh, well, it's kind of a disease, isn't it? You think you can fool them? Yes, that's what marketing is. And it's probably good for that. I just don't like lying to people.
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