7 More Healthy Years: What We Can Learn from Super Agers

1. 0:00 – 0:39

   Introduction

   1. VPVijay Pande0:00

      American healthcare is in crisis.

   2. ETDr. Eric Topol0:02

      We have a path to prevention. It isn't reversing aging. It's just preventing the age-related morbidities of the Big Three. It's been a fantasy for millennia. There should be a reboot, new standard of care based on intelligent partitioning of risk. Seven years more-

   3. VPVijay Pande0:19

      Wow

   4. ETDr. Eric Topol0:19

      ... of health span free of the major three diseases.

   5. VPVijay Pande0:22

      Wow.

   6. ETDr. Eric Topol0:22

      Seven years? Who wouldn't take seven years? [laughs] I hope we'll seize this opportunity because we may never get another one like this for a long time. [upbeat music]

2. 0:39 – 2:05

   Super Ages

   1. VPVijay Pande0:39

      So you've written this really exciting book, Super Agers: An Evidence-Based Path to Longevity, and I think it's a very timely topic. And I was curious for you to maybe set the stage for why you wanted to write it and how you see it in the context of other books that have been coming out recently as well.

   2. ETDr. Eric Topol0:55

      Yeah. There were a few things that came together. Um, we had done a big study we called The Wellderly, where we basically found very little in the genomes of people who had gotten to the age of eighty-seven on average with never having had an age-related disease. So that was, of course, one thing that was part of it. The second was I got inspired by a patient I saw recently who was ninety-eight and had never been sick, and her name is Leigh Risol, and her relatives had died in their fifties and sixties.

   3. VPVijay Pande1:28

      Wow.

   4. ETDr. Eric Topol1:29

      That's her parents, her uncles and aunts. She was the outlier. I say, "Why?" And then there were the books-

   5. VPVijay Pande1:35

      Mm-hmm

   6. ETDr. Eric Topol1:36

      ... that came out. Um, I had patients r- um, coming to me. You know, they wanted me to write a prescription for apamycin or order a total body MRI. I said, "Wait, you know, we, we gotta get the story straight." So these three things together were the, were the impetus that why don't I really get deep into this, everything we know today, and then kinda see if I could lay out some blueprints for where we can go.

   7. VPVijay Pande2:01

      It's coming into a world where American healthcare is

3. 2:05 – 4:42

   Current State of American Healthcare

   1. VPVijay Pande2:05

      in crisis, and I was curious to get your take on where we are now in, in healthcare in the US, and where do you think we could get to?

   2. ETDr. Eric Topol2:12

      Yeah. So there is this bifurcation, as I see it. You could call it, like, the grand slam, where you get reversing of aging, so you keep people healthy or body-wide, and that's where we see all this remarkable investments in companies like Altos and with, uh, reprogramming senolytics and a, and a long list. But they're really focused on a, a monumental task which hasn't been shown in people-

   3. VPVijay Pande2:38

      Right

   4. ETDr. Eric Topol2:39

      ... but rather in rodents. The other side of this is we've made these big strides in the science of aging with all these layers of data that are using the metrics of aging, and why don't we use that to prevent the age-related diseases, cancer, cardiovascular, neurodegenerative? We've never done that in medicine to any appreciable extent, and this is the opportunity [laughs] because we have a path to preventing disease. It isn't reversing aging. It's just preventing the age-related morbidities of the Big Three.

   5. VPVijay Pande3:14

      I think that's something that a lot of people may not realize, is that the, the Big Three that you mentioned, cancer, um, heart disease, and-

   6. ETDr. Eric Topol3:21

      Alzheimer's

   7. VPVijay Pande3:21

      ... Alzheimer's-

   8. ETDr. Eric Topol3:22

      Heart disease

   9. VPVijay Pande3:22

      ... yeah

   10. ETDr. Eric Topol3:22

       Yeah

   11. VPVijay Pande3:22

       ... uh, and, and dementia, uh, that they're greatly a- exacerbated by age. And it, it's interesting because if you ever sort of wanted to have something that could be a, a cure for multiple diseases, which would be the, one of the holy grails of medicine, it would be understanding the a- biology of aging. Where are we now in terms of things that we can use today?

   12. ETDr. Eric Topol3:42

       It takes twenty years to get these diseases, with rare exception. You know, heart disease, uh, almost all cancers, and neurodegenerative, they are incubating for a very long time. They all have a common thread of a defective immune system and inflammation underpinning. They, uh, are preventable, uh, invariably, so cardiovascular, eighty, ninety percent from lifestyle and related factors, modifiable factors, like your LDL cholesterol, that kind of thing.

   13. VPVijay Pande4:18

       Right.

   14. ETDr. Eric Topol4:19

       And cancer and neurodegenerative, just from what we know today with lifestyle factors, we're about half that can be prevented. So we have some knowledge about s- uh, averting these diseases, but we have a lot more with all these clocks and new layers of data that are really changing the face of all outgrowths of understanding the biology of aging.

4. 4:42 – 5:54

   The Role of AI in Health

   1. VPVijay Pande4:42

      So you, in your book, outline the five dimensions of health, and I was wondering, maybe you could walk us through them.

   2. ETDr. Eric Topol4:47

      Yeah. Yeah, sure. F- so the first, uh, uh, most important one i- is AI, because you need that to pull all this other data we're gonna talk about together. This moment that is so exciting is because we have multimodal AI, not only in large language, but large reasoning models.

   3. VPVijay Pande5:05

      Well, and especially I think when you're talking about AI, it's all the things people have seen with generative AI and so on, but also just the ability to understand all this data-

   4. ETDr. Eric Topol5:12

      Yes

   5. VPVijay Pande5:12

      ... that you're measuring from people.

   6. ETDr. Eric Topol5:13

      Yeah, because the other four are such big domains or dimensions. So the omics, it includes not just gene sequence or arrays, but it, it has all the proteins, all the proteomic panels that we can get, which we never could get before inexpensively. It includes the gut microbiome, metabolome, and certainly epigenome or epigenetics. So the omics are rich.

   7. VPVijay Pande5:39

      Mm-hmm.

   8. ETDr. Eric Topol5:39

      We are now seeing moving in towards things like the virtual cell. Then there is, of course, cells that have become a live drug-

   9. VPVijay Pande5:49

      Mm-hmm

   10. ETDr. Eric Topol5:49

       ... where we can reset the immune system and cure autoimmune diseases like we've never

5. 5:54 – 7:59

   Revolutionary Advances in Immunotherapy

   1. ETDr. Eric Topol5:54

      done before.

   2. VPVijay Pande5:54

      So could you give examples of that?

   3. ETDr. Eric Topol5:56

      Yeah. So in the last couple years we've seenUnprecedented cures. We, I mean, never had anything lupus-

   4. VPVijay Pande6:04

      Mm

   5. ETDr. Eric Topol6:05

      ... progressive systemic sclerosis even cases of multiple sclerosis dermatomyositis. So basically, it's depletion of all the B cells, and when they come back-

   6. VPVijay Pande6:17

      Mm

   7. ETDr. Eric Topol6:18

      ... they have forgotten what they were attacking.

   8. VPVijay Pande6:20

      Wow.

   9. ETDr. Eric Topol6:20

      It's amazing. [chuckles]

   10. VPVijay Pande6:21

       Yes.

   11. ETDr. Eric Topol6:21

       It's really amazing.

   12. VPVijay Pande6:22

       And that leads to the autoimmune reaction?

   13. ETDr. Eric Topol6:24

       But the bigger lesson is we have learned how to control our immune system-

   14. VPVijay Pande6:28

       Mm

   15. ETDr. Eric Topol6:28

       ... uh, like a rheostat, and we're gonna keep getting better and better as we measure our immunome. But when you can do that, when you can, you know, quash an autoimmune disease, or when you're trying to cure a cancer by just whatever it takes to keep bringing up that immune system specific to the tumor, the immune system is fundamental, and that also now is involving cells and vaccines. So vaccines now are capable of cures of pancreatic cancer, kidney cancer with these personalized vaccines using the proteins of the person's tumor.

   16. VPVijay Pande7:05

       Yes.

   17. ETDr. Eric Topol7:05

       And-

   18. VPVijay Pande7:06

       And these are in clinical trials right now.

   19. ETDr. Eric Topol7:07

       Yeah. I mean-

   20. VPVijay Pande7:08

       Yeah

   21. ETDr. Eric Topol7:08

       ... the, uh, stuff like we've never seen, you know?

   22. VPVijay Pande7:10

       Yeah.

   23. ETDr. Eric Topol7:10

       And that's just a front runner of what vaccines... That's to treat cancer. We're gonna be using vaccines to prevent cancer. Again, as we get older, some of us especially, our immune system is getting senescent and weak-

   24. VPVijay Pande7:24

       Mm-hmm

   25. ETDr. Eric Topol7:25

       ... and a vaccine before there's any cancer, before there's anything, uh, else, could prop it up. We also have drugs to modulate our immune system well beyond checkpoint inhibitors.

   26. VPVijay Pande7:35

       Mm-hmm.

   27. ETDr. Eric Topol7:36

       And so, you know, whether it's antibody drug conjugates or, uh, tumor-infiltrating lymphocytes and all these different ways, it's hard to imagine that in the future we're gonna lose people with cancer because of being able to bring their immune system to the highest level at, when we need it. But more importantly, preventing the cancer. We can do that now. That's what's exciting.

6. 7:59 – 8:54

   Beyond Diet and Exercise

   1. VPVijay Pande7:59

      Well, and so if we put all this together, what does this mean for the individual? Like, how would their life change? What, what should people be doing?

   2. ETDr. Eric Topol8:07

      Yeah. So I call it lifestyle plus.

   3. VPVijay Pande8:10

      Mm-hmm.

   4. ETDr. Eric Topol8:10

      It's a lot bigger than diet, sleep, and exercise, which, you know, we can drill down on, but it's involving, you know, all the environmental burdens, air pollution, um, the plastics, microplastics, nanoplastics, and forever chemicals. And then there's other things like time in nature. So if each of us [chuckles] did, pulled out all the stops for the lifestyle factors, which is a long list, that will help, but it's not gonna be only lifestyle factors that are the ways to prevent the big three age-related diseases.

   5. VPVijay Pande8:44

      You know, you described a large range of things-

   6. ETDr. Eric Topol8:46

      Yeah. [chuckles]

   7. VPVijay Pande8:46

      ... from the sort of most s- almost sci-fi like, uh, drugs that are in trials for preventing cancer to lifestyle.

7. 8:54 – 20:04

   The Impact of AI on Chronic Diseases

   1. VPVijay Pande8:54

      I could also imagine AI coming into this because one of the things AI is very good at is to take a set of data, and maybe you can mask out the last bit. So you can maybe have someone's health records over 30 years and train on that, except for the last five years, and see if you can predict the last five from the first 25. And once it gets really good at that, you can take my records and say, "Hey, look, Vijay, if you don't do anything, this is where you're gonna be."

   2. ETDr. Eric Topol9:18

      Yeah.

   3. VPVijay Pande9:18

      And we have 99% confidence on this. That would be pretty chilling.

   4. ETDr. Eric Topol9:22

      Yeah. Well, you're exactly right because the, the pinpointing here about the timing-

   5. VPVijay Pande9:28

      Yeah

   6. ETDr. Eric Topol9:28

      ... is so extraordinary. For example, with Alzheimer's, you get a p-tau 217. It's modifiable by lifestyle. You check it again in, you know, six months or a year. Now you have two data points-

   7. VPVijay Pande9:40

      Mm-hmm

   8. ETDr. Eric Topol9:41

      ... and you could say, y- you know, with all the other data that's available, when you're gonna see 18 years from now, 12 years, four years, mild cognitive impairment, unless these steps are taken. This was fully dependent on AI-

   9. VPVijay Pande9:56

      Mm

   10. ETDr. Eric Topol9:56

       ... on models that can, you know, just take all this data. If we didn't have the, the science of aging and the AI, we'd be nowhere. We wouldn't be talking about this today. I wouldn't have written a book.

   11. VPVijay Pande10:08

       Yeah. Well, and it's important for people not familiar with the term of health span, that's basically not just lifespan, but how long you can be healthy.

   12. ETDr. Eric Topol10:14

       Yeah. I don't think we really wanna get to, uh, some age and be demented or compromised. What we're talking about is if you don't have heart disease, cancer, or neurodegenerative, you're pretty darn intact. You may have some achy joints and-

   13. VPVijay Pande10:29

       Yeah

   14. ETDr. Eric Topol10:29

       ... other matters, but those are the things that really interrupt, uh, uh, end our health span.

   15. VPVijay Pande10:36

       Maybe let's turn to another aspect of it, which is the chronic disease aspect.

   16. ETDr. Eric Topol10:40

       Yeah.

   17. VPVijay Pande10:40

       I mean, when we're talking about chronic disease, we're talking typically about diabetes, um, heart disease, cancer. How do we start to make an impact in that? I don't know if you wanna pick one or if you wanna start with cancer.

   18. ETDr. Eric Topol10:51

       I think we can make a huge impact in cancer because we have just simple polygenic risk scores for all the common cancers that that's like one layer of data to say you're at higher risk, and we have multi-cancer early detection tests-

   19. VPVijay Pande11:04

       Mm-hmm

   20. ETDr. Eric Topol11:04

       ... that can pick up microscopic cancer. Why people would get a total body MRI when you could find microscopic cancer, not a mass on a MRI-

   21. VPVijay Pande11:13

       Yeah

   22. ETDr. Eric Topol11:13

       ... which may or may not be cancer. So we have some tools for cancer, but the one thing that I think is unanticipated is the GLP-1 drugs.

   23. VPVijay Pande11:25

       Hmm.

   24. ETDr. Eric Topol11:26

       Uh, the Ozempic, you know, uh, Zepbound world-

   25. VPVijay Pande11:30

       Yes

   26. ETDr. Eric Topol11:30

       ... it's the most momentous drug class in medical history, and we've only seen part of the story so far. You know, in the book, I write about how it took 20 years to figure out that it wasn't just about diabetes, which is amazing.

   27. VPVijay Pande11:44

       Mm-hmm.

   28. ETDr. Eric Topol11:45

       What if we had a AI today and said-

   29. VPVijay Pande11:48

       [chuckles]

   30. ETDr. Eric Topol11:48

       ... "Should we test this for obesity?" Because the developers, Novo Nordisk and later Lilly, of these drugs, they only saw three or four pounds that people with type 2 diabetes would lose with these drugs. And this woman in, uh, Norway, scientist, uh, Lotte, uh, Knudsen, she kept pushing-We gotta try it in obesity.
8. 20:04 – 21:19

   The Future of Preventive Healthcare

   1. VPVijay Pande20:04

      So let's maybe shift gears to talking about the future. So, um, what do you think ... Let's say assume things work out well.

   2. ETDr. Eric Topol20:11

      Yeah.

   3. VPVijay Pande20:12

      That people-

   4. ETDr. Eric Topol20:13

      I hope so. [laughs]

   5. VPVijay Pande20:14

      S- s- p- and what is the best case scenario that you think is, is plausible? Like, what's the science that's coming on the horizon? Let's say we all decide to, to, to make this shift towards prevention and chronic. W- what, what do you think we will get for it in our next five to 10 years?

   6. ETDr. Eric Topol20:29

      Well, I mean, I think you'll, we'll start to see that people are eventually getting to much older ages than we are now without these t- three major diseases. I think that's a gradual thing. It's not like we're gonna see a light switch here.

   7. VPVijay Pande20:44

      Mm-hmm.

   8. ETDr. Eric Topol20:45

      But that's what will be the trend. And we will see countries that will implement it because they don't have the obstacles that we have. Um, we'll see much less of that and the shift, the, you know, bending this curve to the people that are older and healthier gradually. We're not talking about curing. We're talking about [laughs] preventing. It's a lot better than curing, but it takes time to see the benefit. [upbeat music]

Episode duration: 21:28