- Welcome to "The Minor Consult," where I speak with leaders shaping our world in diverse ways. I'm your host, Dr. Lloyd Minor, dean of the Stanford School of Medicine and vice president for medical affairs at Stanford University. Today, I'm excited to continue our special series called "The Big Idea," spotlighting some of society's most critical issues and transformative solutions that promise to lead us into the future. In this episode, we're asking a bold question, "What is the secret to extending the number of healthy, fulfilling years in the human life?" Our guest is Dr. Eric Topol, he's a cardiologist, scientist, and best-selling author. Currently serving as the founder and director of the Scripps Research Translational Institute, Eric is known as a pioneer in individualized medicine. Among his many accomplishments is the founding of the Cleveland Clinic Learner College of Medicine. Eric's latest book, "Super Agers: An Evidence-Based Approach to Longevity," was published earlier this year. It delves into the latest science about aging, including insights from his Welderly study of more than 1,400 people who reached 80 without chronic diseases. Eric's findings and his continuing research led to a big idea, "Can we control how well we age through key lifestyle choices around diet, exercise, sleep, environment, and preventive medical care?" It's an idea that has the potential to transform how we think about aging, prioritizing not just our lifespans, but our health spans. Welcome to "The Minor Consult," Eric.

- Oh, great to be with you, Lloyd, really, I know we're gonna have a fun conversation.

- Indeed. Eric, maybe we could start with the origin of your research on healthy aging, what made you decide to focus on this topic and why is it particularly timely now?

- Right, well, this idea of the Welderly, or really now, we call 'em "super agers," was born when genomics was the height, where we thought everything was due to genetics, genomics, and we could sequence, so we took seven years to find people, their average age was 89, ranged up to 102, who had never been sick or no medication, it's hard to find these people, and we did whole genome sequencing and we compared them to elderly people, the people over 65, with at least one, if not more chronic diseases, we controlled... We compared 'em to lots of different populations and we didn't find that genetics had much of a contribution, at least from their genome sequence, so since then, I think we've learned a tremendous amount of what does constitute the underpinnings for healthy aging, and it turns out it's really not just luck, although there might be a little bit of that, it's really our immune system, and as you mentioned, Lloyd, all these things like lifestyle factors, environmental burdens, they all work through the same mechanism of either dysregulating our immune system or our aging, losing our protection, so the... What we believe is the case now, we want to get to healthy-aging people, 85-plus, no cancer, no neurodegenerative disease, no cardiovascular disease, we have to pay a lot of attention to keeping our immune system with high levels of integrity.

- That's, of course, a really exciting field, and there have been such advances in human immunology over the past decade, can you describe some of those and how your research has been guided by fundamental research and immunology as well as some of the immunological factors that you found in your studies of the healthy-aging compared to the not-so-healthy-aging?

- Right, right, yeah, I mean, this is really fascinating because clinically, as you know very well, Lloyd, we don't have a way to assess the immune system in patients, we, you know, could look at their complete blood count and say, "The white-cell-neutrophil-lymphocyte ratio," that's almost worthless, so we are at a loss, and it turns out that one of your colleagues at Stanford, Tony Wyss-Coray, and a team that he pulled together, they really pioneered these organ clocks, and one of the organ clocks, besides the brain, heart, artery and liver, was the immune system. It may be not considered an organ, but a vital system, and this unlocks something we've never had before, which is the immune system pace of aging, is it slower than the person's chronologic age or faster? So we have a whole new way now to... At least at the moment, we're gonna have even better ways to assess a person's immune system, and everything... It looks like the people who have healthy aging or, you know, particularly, they practice, you know, anti-inflammatory diet, they have great sleep health, they do all sorts of exercise, another great insight from Stanford, by the way, from you and Ashley, and his colleagues there, anyway, it works through the same mechanism of preserving the functionality, the ideal status of the immune system, so finally, we have a way to at least get a crack there with some plasma proteins, it should be very inexpensive, and I expect it will be a part of the routine assessment of patients, particularly as we get older in the future.

- You know, Eric, the desire for us as humans to live a long, healthy life is not new, how were scientists and physicians approaching this goal in the past, and what were they getting right and what were they not able to decipher, either because they didn't have the tools or they weren't focused on the right areas of approach?

- Yeah, I mean, we've had this fixation on the genome, that everything has to be, you know, determined in some way, that it's the barcode of our existence, I think that's been terribly overemphasized, it obviously contributes, but we... Over time, we've learned so much more than that, and particularly as I mentioned with regard to these organ clocks, these are from proteins, not the genes per se, and the immune system, to really study that, you have to do perturbation, you can't just look at, you know, whether it's just the proteins or genes, you have to really test a person's... How their white cells, lymphocytes respond, how their antibody production responds to stimuli, and so, again, another really great paper from another Stanford... You'd think all the work comes from Stanford, but a lot of it is, Scott Boyd and his colleagues there published in Science last year, they did T-cell and B-cell sequencing, which is another way to get real informative data about a person's immune system status, and they found how important that was, so we're... And they did perturbations, of course, they looked at, you know, for example, after COVID and after... Various other ways to, you know, activate the immune system, so we have learned a lot, there's a lot of now immune, age-related assessment that really tell us that if we're gonna make a big change here, and I think we can, and go into an era of preventive medicine like we've never had before, preventing these three major age-related diseases, we have a path forward, and I think it's remarkably exciting.

- Can we talk some about the Welderly study? I think you started enrolling patients... People... Volunteers in this study in around 2016, you mentioned earlier that it was hard to find people your inclusion criteria included, they had to have no chronic diseases or no medications, so it was a herculean effort to recruit the people, but can you walk us through the types of analyses? You mentioned whole genome sequencing, but recently, and you talk about this in "Super Agers," what types of studies have you focused on, and what characteristics have you seen in this cohort of now about 1,400 people who are super agers and who are doing really, really well in some high chronological years?

- Yeah, so I started the "Super Agers" book presenting a couple of patients of mine, one of whom is 98 and is remarkably intact, but what's interesting about her and so many of the family... Or the lineage of people in the Welderly, so she's 98, but her parents and her two brothers died in their sixties or younger, the point being is that we should have known, looking at these families, that the pattern doesn't fit genetics. That their health span and lifespan is distinct, and what we did see in the pattern is, like, with her, she takes remarkably good care of herself, very physically active and, you know, the types of food that she eats, the fact that she has, you know, good sleep, that she has a great social network of her friends that I reviewed, so it turns out the question, of course, is that because she's aged well that she can do all these things, or were her healthy lifestyle behaviors is what led to her super ager status? And I think the more and more we've learned about this, it's that the determinants of the immune system are coming from lifestyle factors, and, of course, it's not just the big three that we used to always consider, we've learned a lot more about those big three, but it is all these other things like having social engagement, like, avoiding as much as possible environmental toxin, specific issues about the food and diet, being out in nature, having hobbies, and purpose, and all these other things, so that... And a very sunny disposition, if there's one thing we learned from these 1,400 people in the Welderly, they're very upbeat, and again, you can say, "Oh, well, Lloyd, oh, they're just upbeat because they're, you know, 90 years old and they're healthy," no, I think, again, they were like that all their life, so, you know, trying to maintain that kind of optimistic persona is all another quality about these people.

- Eric, your book also has a lot of advice for people, it, in a sense, can be used as a guide for people who want to have healthy aging, for people who aspire to be super agers, can you walk us through some of the points based upon where a person is at the time they're reading and seeking advice from your book or other sources, some of the ways they can alter their lives, and how do those change during lifespan or health span? So is your advice, for example, to someone in their 20s different than the approaches and...? What someone in their 50s and 60s should be doing?

- Yeah, I mean, I think... So there's some general features, so in the book, I cited a number of studies that show if you take on all these healthy lifestyle... I call 'em lifestyle-plus because it's not just the diet, exercise, sleep, but many more, that you gain seven-to-10 years if you start at age 50, so that's a lot of healthy years, healthy aging, if you start earlier, you'll gain even more, you can infer that, and, of course, it's never too late, you gain something by adopting these things, so I think, you know, what the research shows now, and there's quite a body of evidence, is that we have a great way to affect our aging process, you know, to promote its healthy health span, to prevent these major age-related diseases, so it comes down to... You know, people have been working, particularly in biotech, to reverse aging, many, many companies are working on that, but there's another path here, and they say, "We'll accept that we're gonna age, it's not a disease, but we can modulate the age-related risk of inflammaging," the inflammation that increases as we get older, in some people much more marked than others, "And immunosenescence," the attrition of our immune system's functionality as we get older, so if we work on those, one of the great ways to do that is, you know, for example, a diet that's considered anti-inflammatory, Mediterranean, largely plant-based, avoidance of red meat and other things that are known to... Not total avoidance necessarily, but decreased consumption, sleep health, which is getting as much deep sleep, sleep regularity, these things are not only important for the brain, but they help to reduce cancer and cardiovascular disease, surprisingly, so getting sleep regularity is a really important goal and we don't pay attention to the fact that we should be on a schedule for... And trying to promote the deep sleep, which is when our glymphatics clear all these waste products from our brain each night, otherwise, we wind up with inflamed brain to some extent, and then, of course, the exercise, this, I think, has been a big jump, we used to... And as a cardiologist, I was obsessed about aerobic exercise with my patients and my own life, but now, we know that resistance training, balance training, they're equally important and they need to be incorporated, so those things are for everybody, but as you know, it's hard to get everybody to do these things, in fact, 75% of Americans are not even meeting the basal physical activity recommendations, not even close, so that's why I think we have to be very individualized when we assess a person's risk and find out which of these three major diseases, and for example, if it's cancer, which cancer, to define it, which we can do now and we never were able to do that previously, that's what's so distinct about where we are right now.

- If we zoom up a level from the health and wellbeing of individuals to the health and wellbeing of populations, and you've addressed this in some of your remarks thus far, but how should we be thinking about systemic changes in public health, things we could do in support of the health of populations? What are the things that are top-of-mind for you in that regard, and what are some of the challenges that we face in making those changes?

- Yeah, so today, what do we do to prevent diseases? Very little. We do try to prevent, like, infections, you know, older people should get a pneumococcal vaccine or shingles vaccine, they may get a lipid panel, you know, but we... It's very minimal, we don't prevent diseases, and we certainly don't prevent cancer or neurodegenerative disease, to a small extent, we do that with cardiovascular by getting on top of risks like lipids, but we really... Still, there's, you know, millions of heart attacks around the world every year, and need for stents, and bypass surgery and whatnot, so the point is, right now, we can change that, completely, radically change that, and what I would say is that each person should have polygenic risk scores, they're very useful, not as a single layer, because they could be a mistake, but if it lines up with the organ clocks, that's really important, we could have total body clocks, you know, methylation, for example, but we have to find a person's risk where... Pinpoint their risk, particularly as they get to age 50 and beyond, when these things crop up, it could even start, you know, earlier, I hope, but this is all part of a multimodal AI layering all this data with their electronic records, their images, their labs, which oftentimes as physicians, we, like the patients, we look through the labs and we don't see an asterisk, and say, "Oh, everything looks good," well, turns out AI will pick up trends in the labs within the normal range, and that's important, for example, we've already seen how that can pick up cancer very early-risk, but anyway, everyone should have this risk assessment as part of their layers of data as we get older, and with that, a check on their immune system, you know, as we get past age 50, maybe even earlier, again, each year, we would get an immune clock, system clock or other means of assessing our immune system, that's how we start preventing diseases because then, we can say, "You know, Mrs. Jones, we're seeing your immune system is compromised in terms of what we would expect, it's not ideal, and we also see you're at risk for this cancer, and it's very hard for you to get metastatic cancer if your immune system is intact, so we're gonna do a multi-cancer early detection test, or we're gonna go after that and put you under surveillance, or if you're at risk for Alzheimer's, we're gonna do a pTau-217 and these neuro markers," so each of these diseases has a path forward that we can use to prevent them, and we're actually, Lloyd, gonna start a Alzheimer's prevention trial based on a lot of the things that, you know, I wrote about in the book, and I actually think ultimately, we will be able to prevent Alzheimer's in people at higher risk.

- That's fantastic. You know, Eric, this is not your first book and you've been a prolific writer and thought leader across broad areas of medicine, certainly your home field of cardiology, but also in terms of the use of electronic health records, wearables, and as you mentioned, AI, I was wondering maybe if you look forward five-to-10 years, and you've addressed this a little bit in your answer to the last question that we just talked about, but how do you see everything fitting together? In other words, wearables where we increasingly have the opportunity to get information, not just about our heart rhythm, but about our blood pressure, probably not too far down the road, maybe we'll be able to non-invasively monitor other biomarkers like our glucose, and, of course, as you mentioned, AI brings all of this together, you know, how do you see it fitting together, if you use your crystal ball, you know, five-to-10 years from now, in terms of how each of us will have the opportunity to monitor and to be engaged with our health in ways that we could have only dreamed about in the past?

- Yeah, well, the theme, as you alluded to in the intro, is individualized data, and that is data that's deep, layers of data, and long, longitudinal, and so, now, there's so much data, billions and billions of data points for any given person, that we need AI to help us interpret it, of course, but here's what I think is so remarkable, if you project this and we have an AI that helps discern a person's risk, yesterday, I spoke with Professor Shana Kelly at Northwestern, she's going to have a implantable sensor to monitor inflammation continuously. Now, not every one of us needs that, but again, if you're at high risk for something and you wanna know that your lifestyle is... If changes are working, wouldn't that be nice that all your inflammation's now getting suppressed? And that's... I mean, basically, she's shown in a paper in Science that it's like a glucose sensor, you just put it under the skin and you don't even feel it, and you get continuous on your smartphone, I volunteered to be patient zero for that, of course, but, you know, they can monitor any protein, so we're gonna see wearables not like what we have today, like, the watches, wristbands, and rings and whatnot, we're gonna have sensors that pick up things that we never had before, like, for example, impending heart attack or potential of heart failure, all sorts of things, people aren't real realizing now how sensors are growing up, you know, they're really moving into the future and it's not far away from being inexpensive, you know, widely used, so what I envision is we find people at risk for... Ideally in their 30s or 40s, we give them specific advice about their risk, they're... Given the, you know, ways to monitor that risk, and we go into this new era of prevention that we've never done, we've talked about it for... In... For millennia in medicine, "Oh, we're gonna prevent diseases," no, what we do is treat, treat, treat, and most of that's not very successful and it's usually too late, all right? We have these drugs for Alzheimer's, for people with Alzheimer's, they don't do very much, they cost a fortune, they have PET scans and whatnot, and this is what... This is how we think when we could prevent the disease, the same with the cancer, we do all these screenings, they don't pick up a lot of the cancers and a lot of people don't even have the screenings, this is not the way, we can prevent these diseases, let's get on it, that's my plea.

- Eric, you've described, and others have described your research as empowering because it identifies actions that each of us can take to delay disease, and I'm wondering, how have the ideas that you've talked about, studied, written about in "Super Agers," how have these changed your personal outlook on aging?

- Well, I used to think before we did the Welderly study that I was destined to be... You know, have cancer because that's... Run in my family, I didn't have any relative that had past the age... In their 60s, so I figured, "Well, you know, I'm not gonna be around too long," well, it was liberating to see from our study that it's not just the genes and the family history, there's much more to this, and so, you know, I've always been attentive to at least aerobic exercise and, you know, a diet that was sensible based on the evidence, and... Like, for example, I haven't had red meat for 40-some years at all, but also the idea I had to really gear up to have better sleep, I was a terrible... If you looked at my deep sleep, you'd say, "Oh, this is horrendous," you know, the set up for, you know, a person with neurodegenerative disease, so really working on that with tracking it, and I think that's something people at least should know about, you know, and it isn't just that you sleep eight hours, no, it's... Or six hours, maybe you sleep six hours and you get an hour of deep sleep every night, that's pretty good, and also, you know, strengthening and balance exercise, which I wasn't doing, and now, I'm, you know, really into that, so these are things that everyone can incorporate, but I did find out, you know, what my risks were, and for example, I... Polygenic risk score for heart disease was very high, you know, in the 96 percentile, I didn't expect that 'cause my... None of my family had heart disease, but, of course, they didn't live that long, and that's one of the things with polygenic risk score, it's just tells you, "Yes," "No," it doesn't tell you when, that's why we need these other layers of data to give us much more temporal informativeness, so anyway, you know, that was important 'cause you'd be more aggressive about, you know, my lipoproteins, that sort of thing, and I have been... So we can all learn from tools that are available today or will be very soon, like the organ clocks, to be able to get right on top of our risk and prevent or at least delay them for decades, you know, it's that sort of thing, so we should be doing that. I'm doing it.

- Fantastic. Well, this has been a wonderful conversation, and Eric, I wanna end with two questions that I ask all my guests, and for this series, I'll add a twist. First, what do you think are the most important qualities for a leader to pioneer a transformative approach to human health?

- Well, I mean, it is thinking in a unbridled way, I mean, you know, you're trying to pick out these big ideas, we should all be thinking big, you know? And act even bigger, that's the key, it's... You know, you just... You have a big idea, but if it just sits there and doesn't ever get out and doesn't ever get worked on, validated, implemented, then what good is it? So I try to work with the crew, I have the privilege of having on our team at Scripps Research, to do that and just, you know, be... What we've learned, if anything in recent years is there's no limits to the use of AI to improve healthcare, and yes, there are many liabilities, we both would acknowledge that, but, you know, we never would've expected that superhuman eyes could pick up things in scans that were inconceivable that humans could see, but they are, you know, making accurate detections of all sorts of things, opportunistic, if you will, and so, that's what we should be doing, is thinking about these tools we have which are new and how we can apply them, and I do think that the biggest... What will turn out if we fast-forward a decade from now, it always takes longer than I hope, that we will see that the biggest jump of impact of AI was in forecasting people's health and preventing diseases, and people haven't been talking about that, they keep it talking about AI for drug discovery, AI for accuracy of diagnoses, AI will help in those things, it will help synthesize a person's medical records and interpret a scan better than a... A image specialist or a pathologist, but this, I think, is the biggest thing and it just came out of just unrestricted thinking, which we all should be engaging in.

- And finally, what gives you hope for the future?

- Well, I mean, I'm a little, of course, challenged, like all of us, about what's happening with the support of research, or what could happen, and, you know, the things that are taking on what I think are really... Is really good science, important science in life science and medicine right now, however, every day, I see advance, I try to put 'em out there, you know, whether it's on X or Bluesky or Substack, the science will not get suppressed, and there's so many great minds out there that there's no way we're gonna hold them back, so I see acceleration of where we are now and that will override the concerns regarding, you know, whether it's the funding or the anti-science movements, whatnot, so I remain very optimistic, I try to share that so that people don't get downbeat about things because so much great stuff is happening in... All throughout life science, all throughout, you know, medical research, and I hope that we're not gonna see any compromise of that, I don't expect it, actually.

- Well, Eric, thank you so much for joining today and for this enlightening conversation, and for all that you do in your research, in your writing, and in your impact as a thought leader, and thank you for listening to "The Minor Consult" with me, Stanford School of Medicine dean Lloyd Minor. I hope you've enjoyed today's discussion with Dr. Eric Topol, author, cardiologist, and director of the Scripps Research Translational Institute. Please send your questions by email to "The Minor Consult" at theminorconsult.com and check out our website, theminorconsult.com, for updates, episodes, and more. To get the latest episodes of "The Minor Consult," subscribe on Apple Podcasts, Spotify, or wherever you listen. Thank you so much for joining me today, I look forward to our next episode, until then, stay safe, stay well, and be kind.