This transcript has been edited for clarity.
Robert A. Harrington, MD: Hi. This is Bob Harrington on the heart.org | Medscape Cardiology, doing my regular podcast. And one of the things that I’m always interested in over the years is talking to physician colleagues who, in addition to physician scientists, happen to be authors. And I’m really privileged this time to be able to interview my longtime friend and colleague Dr Eric Topol about his new book, Super Agers: An Evidence-Based Approach to Longevity. Eric is the executive vice president and professor of molecular medicine at Scripps Research Institute in La Jolla, California.
Eric, thanks for joining us here on the heart.org and Medscape Cardiology.
Eric J. Topol, MD: Pleased to be with you, Bob.
The Genesis of Super Agers
Harrington: Eric, this is your fourth book. Well, let me rephrase that. It’s your fourth book for a lay audience. You’ve got a series of textbooks and other things that many of us have used over the years, but I think I’ve interviewed you now for every one of your books and I’m greatly appreciative of that. I’m a big fan of yours, both from a science perspective but also from a communications perspective. There’s a lot for all of us to learn in how you communicate scientific information. The book is Super Agers, and Eric, what I’m gonna do is actually start at the end. Now if this was a novel, I wouldn’t start at the end because I’d be accused of ruining the ending for people. But this is not a novel; it’s really a very great discussion of what does it take to live a long, healthy life.
But in the end, I was wondering why you wrote the book, because it’s a bit of a departure from the other three. And in this one, I got my answer in the acknowledgements. And in the acknowledgments, you said that during COVID you became interested in the notion of providing reliable information. And that really struck you, that your next book should be thinking about providing reliable scientific information to readers, providing it in some ways, in a dense fashion — meaning a lot of literature, a lot of evidence, a lot of data — and providing it well cited and well referenced so that the reader could do their own investigation and go back to the original source.
Do I have it right? Is that what it grew out of?
Topol: Yeah, you really nailed it, Bob. You know, I learned from COVID how important trusted sources are. I never thought I would be involved with that, but I think I also had been following this space and doing research and healthy aging for a number of years, and I saw all the bunk and pseudoscience out there.
And I said, well, what I learned from COVID, how about putting that to this whole healthy aging story? So that’s what was an inspiration to kind of take all the stuff I’ve been curating and fascinated by and put it together with a really strong body of evidence knowing that some of this stuff is pretty dense and tough. So, it would be a challenge to communicate it. But I did the best that I could.
Harrington: Yeah, you did a fantastic job. I mentioned before we came on screen here that on my iBook version of your book, it’s about 1700 pages, of which a solid 700 pages are the citations and the references. I mean, that is an impressive amount of curation, as you’ve said, and so thank you for doing that, because it’s gonna be a reference source in addition to being a fascinating read.
Topol: Oh, you know, I’m using it now. It’s great for me. Whenever I’m looking for a reference to something, it’s all there. Hopefully that’ll hold up for a while, but it’s been very helpful for me.
Harrington: We’re talking about longevity here and healthy living at Weill Cornell, and I’m already recommending it to several of my colleagues who are leading the efforts because there is a lot of great information here and a lot of really great evidence.
Eric, the other thing that I was impressed by is that you’ve been a doctor a long time. You point that out in the book. You’ve been a cardiologist for decades and you’ve had an interesting career. You’re one of the leaders in interventional cardiology. That’s when you and I first met, when I was a cardiology fellow and you were a very busy researcher, interventional cardiologist. But yet you don’t practice interventional cardiology anymore, you’re a general/preventive cardiologist.
And I was fascinated. I thought, when I picked up the book, my bias was: This was all about the people who age in a healthy way successfully. But in fact, you present two different patients. You present a patient who makes it to her 90s without really any major health problems. And then you present one of your patients who, if I remember right, had bypass surgery. You’d put a couple of stents in them. They’d had all sorts of challenges, but they too also made it to 90-something. So, you’re pointing out — which I loved — yes, there’s the true healthy aging and then there’s the, in some ways, miracle of scientific advancement. You want to comment on that?
The Wellderly vs The Elderly
Topol: Yeah, I think it’s really interesting. Both those patients were 98. In fact, the second patient, RP, is gonna be 100 now. I just got invited to his 100th birthday party. He was 98 when I was writing the book. What I was trying to get at is that, yes, there’s been great advances, particularly in cardiology, bypass and PCI [percutaneous coronary intervention] and everything else. He had ablation a couple times for atrial fibrillation. But these are preventable things. Imagine what this guy would be like if we applied the things that we know to prevent his heart disease. I think now we could have prevented everything. So that’s why I tried to bring this all together, to say yes, some of these people are getting through because of our treatments, but we’re not doing a good job on prevention.
And that is what is so exciting right now. We can prevent — if we really go after this — cardiovascular, neurodegenerative, and most cancers: age-related diseases. That is what really gets me going because, here again, the common thread with the other books — the AI and the digital side of this — is that having deep data on each person, deep, long data, that’s the way that we’re gonna be able to prevent these diseases in the future.
And yet more like the first patient, Lee Rushall, who is just an amazing 98-year-old who I refer to many other times in the book. Why don’t we have more “wellderly” or super agers like her? And really, what accounts for her is this incredible immune system story that I started to drill down on in the book because we don’t know how to measure it yet in the clinic. But we are soon gonna have the first tier of that and more to come.
Harrington: When I think about some of the topics, and you’ve covered the Big Three as you call them — of neurodegenerative [diseases], cancer, and heart disease — and trying to figure out ways that we can prevent those. But what I really loved is you left us all with hope. And your second patient, who had a lot of issues — yes, today we might be able to prevent — but he didn’t have that luxury, so to speak. And there’s a lot of people who would say, well, your genes are your destiny. In fact, you point out your genes are not your destiny. There are some diseases for which your genes are your destiny. But for the vast majority of us, there’s a lot of things we can do that can change our destiny.
Topol: Yeah. That was liberating for me having such a horrible family history. But I think, you know, the results of the Wellderly study, of the 1400 people we genome sequenced, and like Lee Russell, where she’s 98 but her parents died in their 50s, 60s. Her brothers died in their 60s, 70s, and she’s the last one standing.
That was the case in lots of the people in our Wellderly study. So, this is not primarily a genetic genomic story. It’s not just luck as some people think. No, there’s an explanation for this, but I think people should really understand that healthy aging is a separate phenotype. It’s not the same as longevity where you could live quite a long life, but it may not be so healthy.
This is a very discreet and in many ways different type of thing that we’re talking about. And people don’t realize that when you get a combination of variants in your genome, DNA variants from your mother and father, that could be very different than from either alone. That combination of these areas, polygenic risk scores, That’s why our genetic arc is so often different than our parents.
Harrington: Well, like you, I was pleased to hear that, because I had a mother who died at age 42, a sudden cardiac death. I’m 64. So, I’ve lived considerably beyond my mother. And a lot of it is preventable. She was a big smoker, had very high lipids, in a time when they didn’t know what to do with that. And as you point out, knowing this and being able to make choices and being able to do things differently makes a difference. And I think that’s a good message for the book.
The Changing Face of Cardiology
Topol: Yeah, I’m really excited that our area of cardiology is the one that is the closest to getting prevented, with all the things that have already been happening and things that are in the pipeline. Like the drugs that are gonna suppress Lp(a) and much easier detection of coronary artery inflammation without any narrowing or stenosis. It’s really an exciting time for our specialty that we are gonna be taking that preventable mission to whole new potential.
Harrington: I like to refer myself as a reformed interventional cardiologist who now does general cardiology. But you made reference to the advanced imaging and to being able to look at plaque and calculate flow and understand what actually goes into that plaque. That, to me, is helping to revolutionize what we do. I mean, we’re gonna almost do away with diagnostic catheterization because you’re gonna be able to do it with noninvasive imaging.
Topol: Yeah, I mean, I think what’s fascinating is here’s with AI kicking in. Firstly, AI of the retina. At some point, everybody will have these on a frequent basis, and you can get the calcium score of the heart arteries through that, you can get the prognosis or forecasting of heart disease from that or stroke with people who are intact.
And then you can do the same for the epicardial fat analysis around the arteries for the inflammation. So, you’re not just relying on things like high-sensitivity C-reactive protein or other inflammatory markers, which aren’t great. So, it’s really an extraordinary time in each of these three age-related diseases.
And that was the key point, that there’s a fixation on reversing aging, which is a much more challenging, daunting objective. The one we have in front of us, which is preventing age-related diseases, doesn’t take on the risk of inducing cancer and all the other things that reversing aging would do. That’s where we have the biggest opportunity going forward.
Health Equity, Revolutionary GLP-1s, and “Inflammageing”
Harrington: In terms of opportunity, there’s four areas that I picked out where I would call Eric bullish on these topics. So, let’s almost do like a Pardon the Interruption — a rapid flow through these four things.
Number one, you’re bullish on health, equity, and access for all. You want to comment on that? Because that’s not necessarily something that people are willing to talk about today. But you lay it out in almost every chapter.
Topol: Yeah, this is a big deal, because the most popular book in this field by Peter Attia, Outlive: The Science and Art of Longevity, which is exceptionally popular, but it was made for the affluent. And we can’t just promote healthy aging in people who are rich. We have to come up with ways that work for everyone and ensure that the people who need it the most are the ones who are gonna derive the benefits. So, I can’t emphasize that enough. And so all the things we have to do with purpose — of not having these inequities get worse but make them much less of an issue.
Harrington: Kudos to you for tackling that one. I appreciated it. It was not just a throwaway; you brought it up all the time, which I really appreciated. The second one is the GLP-1 receptor agonists. These are obviously the hot drugs. But you tell the story — which also for me really reinforced this notion of discovery science — that sometimes just curiosity-driven science brings us to places that we might not have otherwise logically thought about. Talk about the GLP-1s. You’re excited.
Topol: Oh, it’s just amazing. I mean, I tell the story how it took 20 years to figure out that it might work in obesity and the scientist, Lotte Bjerre Knudsen, who kept pushing, pushing, pushing. And now she’s done the same for Alzheimer’s. And we’ll see the results soon for those trials.
But the main thing here is we’re just at the beginning of the gut hormone and the gut microbiome era, because the gut talks to the brain and the immune system: whether it be through hormones or metabolites of bacteria. And so, what we’re seeing with these drugs like Ozempic and Zepbound, this is just a beginning. There’s 10 of these hormones. There’s all kinds of combinations. They’re going into pills. There gonna be hitting on three or four of these hormones, but many at the same time. So, this is really extraordinary, and I think this is why I’m so excited about having new interventions, on top of lifestyle factors that we can work with, so that we can get on top of these three diseases.
Harrington: Yeah, and as you’ve nicely put it, they’re not just weight-loss drugs. They’re drugs that really change a lot about what we do. That, as you say, the brain-gut interface, the microbiome. They’re remarkable.
Topol: Yeah, I’ve never seen in all these years a drug class like this. But just so people realize, this is just still the beginning. There’s so many more in the pipeline, and when we have pills and it’s inexpensive…and it’s something that is easily accessible. Wow. We have never had such a potent anti-inflammatory for the body and the brain, and that’s what’s so really extraordinary here.
Harrington: Eric is bullish on a third thing, which is the immune system and inflammation. And you nicely weave together, with the three major killers, the role that our immune systems play or don’t play and the ways that we might attack that immune reaction through therapeutics — both lifestyle therapeutics, but also drugs. You want to comment on that?
Topol: This is really where it all comes down to. The two terms: immunosenescence, that our immune system as we age is starting to go into decay mode and lose some of its protection and dysregulation, and then “inflammageing.” With that immune system that isn’t right, it’s now secreting cytokines, chemokines, and fostering inflammation. This is the problem with getting older.
We’re all getting older, but if we can keep this immunosenescence and “inflammageing” in check, that’s where we get to healthy aging. And that starts with being able to measure it. An immunotherapy that we need to have that’s inexpensive. And we’re gonna have that soon. One of your former colleagues at Stanford, Tony Wyss-Coray. He’s amazing. He pioneered organ clocks. We’re gonna be getting an immune system clock in people, in part of our clinic evaluation in the times ahead. So we know, as they get older, when they’re starting to go down in their protective or in their self-reactive potential.
So, this is a big change in the field, and I never would’ve thought the immune system — and again, that goes back to the gut too — would be the explanation for healthy aging. But all the lifestyle factors work through it: exercise and our diet and ultraprocessed foods and environmental things, air pollution, forever chemicals and plastics. Whatever you look at, it works through this inflammation-immune system axis.
Artificial Intelligence and Its Role in Drug Discovery
Harrington: Eric, up until this book, my favorite of your previous three was Deep Medicine, and I still recommend it to people who want just an overview of what artificial intelligence might offer us.
I’m gonna get you to focus on one thing. You talk about AI and its role in education. You talk about AI and its role in diagnosing diseases, as we’ve just said. But one of the things that you gave me tremendous insight into was AI and drug discovery, and how it’s really gonna accelerate. And you talk about AlphaFold and the Nobel Prize for the use of artificial intelligence. Talk about AI and drug development, drug discovery; that’s some fascinating work going on.
Topol: Yeah, there’s a lot of negativism against AI. I understand that. But in health and drug discovery, we’re already seeing drugs going into phase 3, taking on fibrosis, whether it’s in the lungs and some other organs. We’re gonna see some things we’ve never had before. And the problem that we have in doing clinical trials, finding the right patients to go in… there’s many nodes of how AI can rev things up. The main thing of acceleration: finding molecules, designing protein, designing monoclonal antibodies, small molecules.
There’s some creativity here. There’s some unanticipated acceleration. You know, we’re saying, well, where are all the drugs? Well, as you know, there was one during the pandemic that was derived from AI. It was a JAK inhibitor baricitinib, which saves lives in people with severe COVID. It was being used for alopecia and rheumatoid arthritis. Who would’ve thought that it would save lives for people hospitalized with COVID. So, we’re gonna see much more of that in the times ahead.
Harrington: I think that’s incredibly exciting and really makes us think about how there are drugs on the shelf that need to be repurposed and maybe AI can help us do that.
Topol: And it’s happening. I mean, there’s a lot of work being done on that same data mining to find the molecules that already exist, that the binding sites that we learned from AlphaFold 3 and all these other large language models of life science. Yeah, it’s happening. And the reason why AI is so big for healthy aging is we are gonna have hundreds of billions of data points for each person. All these layers of data — genomics and proteins and markers and you name it — there’s no human being that can take all that data to find who’s at high risk, to do the surveillance, to be all over it to prevent these Big Three diseases.
Hours of Reading Leads to Prolific Writing
Harrington: Eric, final question. I found this is a question that fascinates me every time I ask one of my physician/author friends to comment on it. What’s your style of writing? How do you find the time? I mean, you are a busy guy. You run a big research institute. You’re a prolific author. You’ve got a lot of your own science going on, your own research group. And yet a book like this, which I mentioned at the outset is so densely referenced and cited and all of the original evidence is there. What’s your style?
Topol: I mean, I love to write. I do the Substack blog Ground Truths, and every week I’m putting something on that. And because I learn when I write, I’ve gotta really go back to the papers. I work often on weekends, vacations…any time I can find a block of hours to do it.
But the basis of it is a lot of reading every day. You know, a couple hours a day at least. And then, whether it’s highlighting or taking notes, whatever. So that when I’m finally doing the writing part, I’ve got the essence of what I’m gonna be getting into culled together. So, I think for me, it’s being organized and always looking for time, and it’s something I really enjoy. Because I learn, and then I’m just trying to share what I learned so hopefully others can also potentially benefit from it.
Harrington: Well, you do a great job at organizing it for the rest of us, and I’ve often thought in the many years I’ve known you that one of your great skills is the synthesis of information and being able to then communicate that synthesis of information in a way that helps the rest of us. It’s a real skill that you obviously have developed and work on over time, and I think many of us appreciate it. I’m often asked how I keep up with the literature. And one of the ways I keep up with the literature is through social media. One of the things I advise people to do is follow people [on social media sites] who have good taste in science.
And I think, Eric, you have good taste in science and really can help inform the rest of us. So, thank you for doing it.
Topol: I really appreciate that. A lot of what I do probably will be eventually taken over by generative AI, but for now I enjoy doing it.
Harrington: We’re glad you’re doing it. And I want to thank you, Eric, for joining us here to talk about your new book, Super Agers: An Evidence-Based Approach to Longevity. I hope that people take the time to read it and to also spend some time, as I’ve been doing since I finished the book, at looking through the references, the citations. Take a look at some of the original data on topics that interest you.
I hope that you’ve enjoyed my conversation with my friend and colleague, Dr Eric Topol from Scripps Research in San Diego and La Jolla, California. Thanks for joining us here, Eric, on Medscape Cardiology and the heart.org.
Robert A. Harrington, MD, is the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine and provost for medical affairs of Cornell University, as well as a former president of the American Heart Association. He cares deeply about the generation of evidence to guide clinical practice. When not focusing on medicine, Harrington dreams of being a radio commentator for the Boston Red Sox.
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Cite this: Unlocking Longevity: Aging Reimagined - Medscape - Oct 07, 2025.
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