Pod Insights a16z Podcast What Super Agers Reveal About Preventing Disease About this episode American healthcare is in crisis—but what if we could change the system by preventing disease before it starts?
In this episode of the a16z Podcast, general partner Vijay Pande sits down with Dr. Eric Topol, founder and director of the Scripps Research Translational Institute and one of the most cited researchers in medicine, to explore the cutting edge of preventive healthcare and longevity science.
Drawing from his new book Super Agers: An Evidence-Based Path to Longevity, Topol breaks down why understanding the biology of aging—not reversing it—is the key to preventing the “Big Three” age-related diseases: cancer, cardiovascular disease, and neurodegenerative conditions. The conversation spans AI-powered risk prediction, organ clocks, polygenic risk scores, GLP-1s, and the cultural and economic shifts required to move from a “sick care” system to one rooted in precision prevention and extended healthspan.
If you’ve ever wondered how data, personalized medicine, and AI can add seven healthy years to your life—and what it will take to bring those benefits to everyone—this episode is for you.
Transcript Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.
0:01 Vijay Pande? American healthcare is in crisis.
0:04 Speaker 01 We have a path to preventing disease. It isn't reversing aging. It's just preventing the age-related morbidity of the big three.
0:14 Vijay Pande? If we can keep people healthier, healthier people would be much less expensive.
0:18 Speaker 01 Seven years more of health span, free of the major three diseases. Seven years? Who wouldn't take seven years? There's just billions of data points for each person. There should be a reboot, new standard of care, based on intelligent partitioning of risk.
0:38 Speaker 01 We have to do better.
0:40 Steph Smith? The human obsession with living longer is as old as time. But in the last 20 years, we have learned so much more about human health and biology. So what do we know today about what makes humans live longer? And do we have real evidence that longevity is an attackable target? Today, you'll get to hear a 16Z general partner, Vijay Pandey, in conversation with Eric Topol, who recently released his new book, "Superagers: An Evidence-Based Approach to Longevity." Eric is, among other things, the founder and director of the Scripps Research Translational Institute. He's also published over 1,200 peer-reviewed articles with more than 300,000 citations, making him one of the 10 most cited researchers in medicine.
1:23 Steph Smith? That resume puts Eric in a perfect position to write this book, teasing the signal out from all the noise around health in 2025. One of those inputs was the Welterly Group that Eric studied, which was a study of 1,400 people, 80-plus, who had never developed a chronic illness. For comparison, according to Eric's book, among those 65-plus, 80% have two or more chronic diseases, and 23% have three or more, while about 7% have five or more. And again, that was the 65-plus group versus the Welterly Group of 80-plus. So what do we know about these, quote, "superagers"? People who not only have a longer lifespan, but a longer health span? Is it genetics or human agency?
2:06 Steph Smith? And do technologies like AI, GLP-1s, gene therapies, or the ability to understand organ clocks meaningfully change that equation for the masses? If so, what difficult decisions do we have to make to rewrite the system today? Let's find out.
2:24 Speaker 03 As a reminder, the content here is for informational purposes only, should not be taken as legal, business, tax, or investment advice, or be used to evaluate any investment or security, and is not directed at any investors or potential investors in any A16Z fund. Please note that A16Z and its affiliates may also maintain investments in the companies discussed in this podcast. For more details, including a link to our investments, please see A16Z.com/disclosures.
2:54 Vijay Pande? My joy to welcome Dr. Eric Topol to the podcast. Eric, thanks so much for joining us.
2:59 Speaker 01 I'm glad to be here, Vijay.
3:01 Vijay Pande? So you've written this really exciting book, Superagers: 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.
3:17 Speaker 01 Yeah, there were a few things that came together. We had done a big study we called the Welterly, where we basically found very little in the genomes of people who had gone to the age of 87 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 98 and had never been sick and...
3:45 Vijay Pande? So never been sick?
3:46 Speaker 01 Yeah, her name is Lee Rissall, and her relatives had died in their 50s and 60s. That's her parents, her uncles and aunts. She was the outlier, and say, why? And then there were the books that came out. I had patients coming to me. You know, they wanted me to write a prescription for apamycin, or order a total body MRI. So we gotta get the story straight. So these three things together were the impetus that, why don't I really get deep into this? Everything we know today and then see if I could lay out some blueprint for where we can go.
4:21 Vijay Pande? It's coming into a world where American healthcare is in crisis. I was curious to get your take on where we are now in healthcare in the US and where do you think we could get to?
4:31 Speaker 01 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 healthier bodywide and that's where we see all this remarkable investments in companies like Altos and reprogramming Synolytics and a long list. But they're really focused on a monumental task, which hasn't been shown in people, but rather in rodents. And some of the results are striking and I hope at least one, if not all of these are successful. The other side of this is we made these big strides in the science of aging with all these layers of data that are using the metrics of aging.
5:13 Speaker 01 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 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.
5:36 Vijay Pande? I think there's something that a lot of people may not realize is that the big three that you mentioned, cancer, heart disease and Alzheimer's and dementia, that they're greatly exacerbated by age. And it's interesting because if you ever wanted to have something that could be a cure for multiple diseases, which would be one of the holy grails of medicine, it would be understanding the biology of aging. Where are we now in terms of things that we can use today?
6:01 Speaker 01 The first and perhaps the most extraordinary thing is it takes 20 years. To get these diseases with rare exception, you know, heart disease, 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 are preventable invariably. So cardiovascular, eighty and ninety percent from lifestyle and related factors, modifiable factors like your LDL cholesterol, that kind of thing. And cancer and neurodegenerative, just from what we know today with lifestyle factors, we're about half that can be prevented.
6:46 Speaker 01 So we have some knowledge about 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.
7:02 Vijay Pande? So maybe let's double click on that. So you, in your book, outline the five dimensions of health. I was wondering, maybe you could walk us through them.
7:09 Speaker 01 Yeah, sure. So the first, most important one is AI. Because you need that to pull all this other data we're going to talk about together. This moment that is so exciting is because we have multimodal AI, not only in large language, but large reasoning models. Now.
7:28 Vijay Pande? Well, 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.
7:35 Speaker 01 Yes.
7:35 Vijay Pande? That you're measuring for people.
7:36 Speaker 01 Yeah, because the other four are such big domains or dimensions. So the omics, it includes not just gene sequence or arrays, but 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. We are now seeing moving in towards things like the virtual cell. Then there is, of course, cells that have become a live drug. Where we can reset the immune system and cure autoimmune diseases like we've never done before.
8:17 Vijay Pande? Could you give examples of that?
8:19 Speaker 01 Yeah, so in the last couple of years, we've seen unprecedented cures. I mean, never had anything. Lupus, progressive systemic sclerosis, even cases of multiple sclerosis, dermatomyositis. So basically, it's a depletion of all the B cells, and when they come back, they have forgotten what they were attacking. It's amazing.
8:43 Vijay Pande? Yes.
8:44 Speaker 01 It's really amazing.
8:45 Vijay Pande? And that leads to the autoimmune reaction.
8:46 Speaker 01 But the bigger lesson is we have learned how to control our immune system, like a rheostat, and we're going to keep getting better and better as we measure our immune immune. But when you can do that, when you can 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. So 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.
9:27 Vijay Pande? Yes. And these are in clinical trials right now.
9:30 Speaker 01 Yeah, I mean, it's stuff like we've never seen. And that's just a frontrunner of what vaccines, that's to treat cancer. We're going to be using vaccines to prevent cancer. Again, as we get older, some of us especially, our immune system is getting senescent and weak, and a vaccine, before there's any cancer, before there's anything else, could prop it up. We also have drugs to modulate our immune system well beyond checkpoint inhibitors. And so whether it's antibody-drug conjugates, tumor infiltrating lymphocytes, and all these different ways, it's hard to imagine that in the future, we're going to lose people with cancer. Because of being able to bring your immune system to the highest level when we need it.
10:15 Speaker 01 But more importantly, preventing the cancer. We can do that now. That's what's exciting.
10:20 Vijay Pande? Well, and so if we put all this together, what does this mean for the individual? Like, how would their life change? What should people be doing?
10:29 Speaker 01 Yeah, so I call it lifestyle plus. It's a lot bigger than diet, sleep and exercise. It's involving, you know, all the environmental burdens, air pollution, the plastics, microplastics, nanoplastics and forever chemicals. And then there's other things like time in nature. So if each of us pulled out all the stops for the lifestyle factors, which is a long list, that will help. But it's not going to be only lifestyle factors that are the ways to prevent the big three age-related diseases.
11:02 Vijay Pande? You know, you described a large range of things, from the sort of most almost sci-fi like drugs that are in trials for preventing cancer to lifestyle. When people think about lifestyle, it's maybe a little vague in their mind for what to do. How do you make that into a science? Or how do you help people take that to the next step to bring evidence into that?
11:21 Speaker 01 I go into perhaps Great Pains, High Density to cite all the studies that link. Like, for example, when you have really good sleep health and deep sleep, what does that do to slow your brain aging? Or, you know, if you drink sugar sweetened beverages, what does that do to specific, not just risk of type 2 diabetes, but, you know, all-cause mortality? So there are very compelling sets of data about lifestyles and these key outcomes. And they're linked to healthy aging. I was amazed at how much data is out there that can help us. It's not just like in the era when we had polygenic risk scores.
12:02 Speaker 01 I mean, you say, oh, your risk for Alzheimer's, but we don't know if when you're age 56 or 96. So what good is that?
12:09 Vijay Pande? Yes.
12:10 Speaker 01 Now we're saying, we know it's within a couple of years between 77 and 79 that you're going to have mild cognitive impairment if we don't do these things, which includes the lifestyle factors. And it's much harder to get people to do a lot of stuff. They have no specificity that's about them.
12:28 Vijay Pande? Yeah.
12:29 Speaker 01 That they can change the arc of a condition, especially when it isn't our genes. The healthy aging story about a genetic underpinning is just not there. We studied that. It's minimal. I mean, maybe it's 10% of what accounts for healthy aging. Most of it is in the lifestyle factors and related matters such as the immune system not functioning properly, too much, too little.
12:54 Vijay Pande? Well, it's generally believed that just telling someone to eat better and exercise doesn't work, but what I'm hearing you say is that you have a way to do that by making it very personalized.
13:04 Speaker 01 Yes, I mean, there was a Finnish study that was on just polygenic risk score, which is rudimentary. And they gave that to a large cohort and they studied whether that affected their lifestyle. And the results were remarkable. The people who got the data stopped smoking, changed their diet, changed their physical activity, really amped it up. So we know when people get data that's specific to them, a large proportion, much more likely to make changes. Now, I'm not claiming that lifestyle is going to be the only part of the prevention story, but once you define the high risk and it's particularized to a person, that's a big part of how we're going to succeed.
13:47 Vijay Pande? 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, you don't do anything. This is where you're going to be. And we have 99% confidence on this. That would be pretty chilling.
14:15 Speaker 01 Yeah, well, you're exactly right because the pinpointing here about the timing is so extraordinary. For example, with Alzheimer's, since we were talking about that, you get a P tau 217. It's modifiable by lifestyle. You check it again in six months or a year. Now you have two data points and you could say with all the other data that's available, when you're going to see. Eighteen years from now, twelve years, four years, mild cognitive impairment unless these steps are taken. This was fully dependent on AI, on models that can just take all this data. If we didn't have 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.
15:00 Vijay Pande? Yeah. Well, 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.
15:07 Speaker 01 Yeah, I don't think we really want to get to some my 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 other matters, but those are the things that really interrupt our health span.
15:26 Vijay Pande? Now, we're talking about healthcare meaning something different. To be preventative, and we'll talk about chronic in a second. How do we help make that mind shift?
15:35 Speaker 01 This is perhaps the biggest point so far that we've been discussing because in medicine, and I've been in it for almost 40 years, we don't do primary prevention. The person has a heart attack and then we get all over it. But for the most part, we don't prevent cancer. We don't prevent Alzheimer's and neurodegenerative diseases. It's been a desire, I would say a fantasy for millennia.
15:59 Vijay Pande? Yes.
16:00 Speaker 01 But we are at a very different point right now. We have a path to prevention, primary prevention, not after somebody has one of these diseases. And that is what is extraordinary. And it was all these recent advances that led to this capability. And we've got to jump on it because it's exciting that we could actually do this.
16:22 Vijay Pande? Well, also, the thing about prevention is that I've talked to doctors who very boldly assert that prevention doesn't work.
16:30 Speaker 01 Yeah.
16:30 Vijay Pande? And I look at them a bit confused because I say, well, there's been numerous examples and they're like, well, name one. I was like, how about smoking?
16:37 Speaker 01 That's the prototype.
16:39 Vijay Pande? Huge incidence of lung cancer, which has just disappeared now because we don't smoke in restaurants or airplanes and so on. But one of the things that I think about about that movement is that while doctors played a significant role in that, that was also very much a cultural movement.
16:54 Speaker 01 Yes.
16:55 Vijay Pande? And so we talked about lifestyle, changing people's behaviors. I think some of this or much of this has to be as much cultural as medical.
17:02 Speaker 01 There's a definite cultural component and tobacco is one of the most impressive, but there's so many others.
17:09 Vijay Pande? Yes.
17:09 Speaker 01 I think what we've learned, like for example, with sleep, I didn't pay enough attention to that. But with sleep, when you promote your own deep sleep, which we tend to lose a lot as we age. Then you see much less dementia, Alzheimer's, even less cardiovascular and cancer related illnesses, cases and mortality, sleep regularity. We need to be more ritualistic about it. And there are many things just on sleep itself, no less about physical activity, about, for example, not just even resistance training, but balance, posture, things like that. So the more you go deep, nutrition especially, we've learned a lot about that.
17:52 Speaker 01 Convincing, compelling evidence, I would say, that you say these effects, we're talking about just with that. Seven years more of health span, free of the major three diseases.
18:03 Vijay Pande? Wow.
18:04 Speaker 01 Seven years? Who wouldn't take seven years? That's just what we know today. Once we can define high risk, which is one of the things we turn to with AI, that changes everything because then you focus on that.
18:16 Vijay Pande? Maybe let's turn to another aspect of it, which is the chronic disease aspect.
18:20 Speaker 01 Yeah.
18:20 Vijay Pande? When we're talking about chronic disease, we're talking typically about diabetes, heart disease, cancer. How do we start to make an impact in that? I don't know if you want to pick one, if you want to start with cancer.
18:31 Speaker 01 I think we can make a huge impact in cancer because we have just simple polygenic risk scores for all the common cancers. That's like one layer of data to say you're at higher risk. And we have multi-cancer early detection tests 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, 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 Glip1 drugs. The Ozempic, Zepbound world. Yes. It's the most momentous drug class in medical history. And we've only seen part of the story so far.
19:15 Speaker 01 In the book, I write about how it took 20 years to figure out that it wasn't just about diabetes, which is amazing. What if we had AI today and said, should we test it 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 Norway scientist, Lata Nudsen, she kept pushing, we gotta try it in obesity. And they wouldn't listen to her because, well, she said, diabetics are not losing weight. They finally did it, and everyone knows the story. 20, 30, 50, 80 pounds of weight loss. Now, when you lose that much weight for people who are obese,
20:00 Speaker 01 you reduce the risk of cancer. You reduce the risk of heart disease and neurodegenerative disease. It wouldn't be surprising to me that now with pills that are remarkably effective to substitute for injections that can be much less expensively, that a large proportion of the population would be taking one of these drugs or even their successors, that is, those that are even more potent and potentially with less side effects. So we have a drug class now added to lifestyle factors we didn't have before. Right. As you know, they are in big trials for preventing Alzheimer's in people who are not overweight. Yes. Okay?
20:42 Speaker 01 We're going to be doing a long COVID trial in people who are not overweight. The effects are really quite extraordinary. The ability to crack obesity. Yes. We would have been happy just to do that. But all the other things that are coming from it? Who would have thought that you could treat, prevent addiction? Yeah, that's remarkable. Yeah. The ability to stop, reduce alcohol intake from heavy intake, gambling. I mean, the list just goes on because we're learning about the brain circuitry and how these drugs. So some of the secrets of the gut-brain axis, which is tied into the immune system and is tied into the science of aging. This is what's given us this newfound potential to change.
21:25 Speaker 01 We don't have to only rely on drugs, but there's this, as we discussed, this kind of interdependence.
21:31 Vijay Pande? Well, and I think having lifestyle infrastructure with these drugs, that combination is particularly interesting. Because you can make sure that you can lose weight while keeping muscle. And also, hopefully, patients can go off the drugs, at least for some periods of time, and not rebound.
21:47 Speaker 01 We don't have encouraging data at the moment because at least half of people gain weight back when they stop.
21:53 Vijay Pande? Yeah.
21:53 Speaker 01 And that's not good. But I do think that we'll come up with a ways to hopefully not rely on such a long-term commitment. The results on muscle mass, we'd been very worried about that. And I think when people combine taking the drugs with strength training, and we do know there's muscle mass loss just with weight alone. But that looks encouraging, even though the companies have been acquiring muscle-making drugs.
22:19 Vijay Pande? Yes.
22:20 Speaker 01 That may not prove to be particularly necessary.
22:22 Vijay Pande? Well, and I think one thing that's interesting is that another knock on lifestyle is if you're extremely obese, telling someone to exercise, it's a hard road.
22:31 Speaker 01 Oh.
22:32 Vijay Pande? To just get started.
22:33 Speaker 01 Absolutely.
22:33 Vijay Pande? And so this could jumpstart a better lifestyle that then could get locked in. That could be really miraculous.
22:39 Speaker 01 I've seen it in many patients, just what you said. Couldn't get them to really increase their activity, but when they were thinner, everything changed. When you think about, if we can make a huge dent, there's nothing more economically favorable for us at the public population health level if we can achieve this.
23:00 Vijay Pande? And so what else would you put into the chronic bucket? I think one of the things that you've written about is AI plus all the things you can track.
23:07 Speaker 01 I think the ability to look at the organ clocks, which was initially reported here at Stanford by Tony Wiss Corry and his colleagues, and now validated and replicated by multiple groups. The fact that we can do that and have the brain, the heart, the immune system, and other vital organs, and we can say, this one organ of yours is five years out of pace with your real age. Then we can integrate that with these other layers of data. Oh, if that's the case, what about your polygenic risk score? Is there anything pointing to that? Disease or organ, we can look at your whole body aging, epigenetic Horvath clock.
23:52 Speaker 01 We can also look at specific proteins, like for example, for the brain, P tau 217. And what's amazing about that protein, which we can get now, and it's not that expensive, but that in itself gives us over a 20-year warning about mild cognitive impairment. It's modifiable exercise and lifestyle. We've seen people in studies that dropped more than 50%, even up to 80%.
24:20 Vijay Pande? It's intriguing that it's not binary too, so you can track the gradient.
24:23 Speaker 01 Exactly.
24:24 Vijay Pande? And that would get particularly scary if it's increasing.
24:26 Speaker 01 So we're talking about in people without symptoms, but are at high risk, having this access, I don't recommend any of these things that we're talking about until you know you have an increased risk. But once you do, then you say, hmm, I can do something about it and change the course of what otherwise would be that person's natural history. But the molecular clocks, this collection of proteins, this is something else that's striking, the O-Link and Somologic, they're between 6,000 and 11,000 plasma proteins. What we've learned from them, the fact that there's three bursts of aging during our life is not just a linear story, and the fact that we're learning about the underpinnings
25:10 Speaker 01 of diseases, but most importantly, we have these organ clocks that are inexpensive to get. The UK Biobank is only paying $50 per participant. And they've done 50,000 and got amazing data coming from it, but another 500,000 is in process. So it's not that expensive to get such rich data. And when you start having genes and proteins and these other layers of data, that's when you find out what is making us unique and what we are at risk for during our extended time.
25:43 Vijay Pande? And therefore what we should do to change it and improve.
25:45 Speaker 01 Yeah.
25:46 Vijay Pande? Well, let's take a step back because I think you've been laying out a very appealing picture for what we as individuals could do to improve our health span, get at least seven more years, easy, maybe more and more and more as the science improves. But you can also think about this from a societal level, that the cost of healthcare is immense.
26:05 Speaker 01 Yes.
26:06 Vijay Pande? Just the cost of healthcare to the US government through Medicare and Medicaid is approaching $2 trillion. And we live in a time where the United States is in massive debt, there's a great desire to reduce the deficit, or make the deficit negative would be ideal. And you look at healthcare and people are scared that healthcare could be cut or something like that. And I think no one wants to remove services. But there is this alternative that is very natural from everything you're talking about, which is that if we can keep people healthier.
26:33 Speaker 01 Yeah.
26:34 Vijay Pande? Healthier people would be much less expensive.
26:35 Speaker 01 Right.
26:36 Vijay Pande? And we could have a win-win. How do we shift the system, whether we're talking about CMS, or we're talking about insurers or providers, how do we shift the sick care system to be thinking about preventative and chronic?
26:49 Speaker 01 We have a barrier here because of the mal incentives. People could change their insurance companies at any time, so the insurance company doesn't have a long view. Whereas other countries, like when I did the review of the NHS for the government there, they're well positioned in the UK. And many countries, except for the US, have a better positioning for this. If we could make prevention, now that it is emerging as a reality, the priority, and say, every insurer, whether it's Medicare, Medicaid, private insurers, if they don't pull out all the stops and make this a priority, then, you know, we have to make some pretty
27:34 Speaker 01 drastic policy changes. We've not actually accepted yet that we have this newfound capability, which completely changes the economics beyond making a case for health span for a population possible. And as the people who need this the most are currently the least likely to get it, to access, and so this is another issue, which, if this only is for the...
28:02 Speaker 01 Affluent. If we don't take care of everyone, we're not going to achieve that goal. So it can't just be for people who can have the assets to get this. It has to be broadly, universally distributed.
28:16 Vijay Pande? How can we translate all the existing programs to something that could be, let's say, rolled out to Medicare?
28:24 Speaker 01 Yeah, I mean, I think that if we negotiated, the AI is software. It could be cheap, whether it's some proteins, a specific protein, polygenic risk score, these things can be done $20, $50 cheaper than most, any lab test that we do right now. If we could develop a package negotiated at a very low rate. One way that's really great, Vijay, about this, we don't have to wait 10 years to see the benefit. If we see the clocks all changing in the right direction.
28:53 Vijay Pande? Oh, that's a great idea.
28:53 Speaker 01 We have an intermediate surrogate endpoint. So like, for example, we use LDL cholesterol to know if we have a person's arteries in check. We're going to have these proteins like P tau 217 say, oh, well, all these preventative approaches are really kicking in. This should change the likelihood of, or ever, developing a neurodegenerative Alzheimer's condition. So we have the metrics again to get a short, quick assessment. Are we making a difference? If we did that through CMS, that would be phenomenal. But maybe we can get one of the big insurers to pilot this to make it possible. If Mamad Oz is listening, maybe he'll get interested. I don't know.
29:37 Vijay Pande? Yeah, I think CMS is interested in what it can do to keep people healthy and reduce cost. That's the canonical win-win. I think also, as you've written about, AI could really have a huge role here too, because prevention's expensive if you have to roll this out with GPs or NPs. But to roll out with AI could be very, very scalable.
29:56 Speaker 01 Yeah, and I think you made a point earlier about the AI is that as we do this, and we do this at scale, it just keeps getting better. So that the ability to predict, pinpoint temporally when a person is likely to develop one of these three conditions with 20 years runway. If we can't do this for these three diseases, we're not too smart. If AI was before, just a few years ago. The capabilities wouldn't be there and neither would these metrics of aging and all the science has done to catapult that. That's what's presented a unique opportunity and if we don't do this, we're just stupid.
30:37 Vijay Pande? Well, actually, let's double click on that because there are a lot of enemies of the future. And maybe a nicer way to put it is that people could be skeptical.
30:47 Speaker 01 Yeah.
30:47 Vijay Pande? And they're used to operating a certain way. They have a certain belief that this isn't going to work for whatever reason. What would you tell them, like to your fellow clinical colleagues, to try to change their mindset from a sick care mindset to a preventive mindset?
31:01 Speaker 01 Yeah, I mean, to me, it's all about compelling data.
31:04 Vijay Pande? Yeah.
31:04 Speaker 01 So, for example, the Alzheimer's drugs, which don't really work and they're very risky, but the reason they were bought into by the FDA ultimately was because the amyloid came out on the scans, right? And they were a little bit of cognitive score improvement. But here we have metrics that are extraordinary to help us as a bridge for compelling evidence. Ultimately, you want to say, we prevented these diseases in people that had definition of their risk and then active surveillance, preventive, pull out all the stops.
31:39 Vijay Pande? Right.
31:40 Speaker 01 For example, speaking about waste, we do mass screening for cancer. We treat everyone as the same.
31:49 Vijay Pande? Right.
31:49 Speaker 01 Based on their age. And that's the only criterion for screening, age. We only pick up 14% of cancers from that mass screening, which costs over hundreds of billions of dollars a year. Now, what about 88% of women will never have breast cancer? Why do 100% of women have to go through this?
32:11 Vijay Pande? And especially with Bay's rule, you could actually use priors that you could measure.
32:15 Speaker 01 And we don't do it.
32:16 Vijay Pande? Yeah, yeah.
32:17 Speaker 01 And this is a corollary of what we're talking about. Why don't we take the risk profile and say, you know what, to a woman or for a person having colonoscopy, you don't really ever have to have it, or you can have this once in your lifetime or twice, whatever. We don't treat people as human beings with particular aspects that we can define today.
32:39 Vijay Pande? And why do you think that is?
32:40 Speaker 01 We're ingrained in stupidity.
32:43 Speaker 01 Maybe when these mass screening programs started, that was the best we could do.
32:48 Vijay Pande? Yeah.
32:48 Speaker 01 But we've known about polygenic risk scores and we've learned now about all these other ways to assess risk and then with added on the AI part of it, we have to do better. But just having the screening part cleaned up would save a tremendous amount of money.
33:04 Vijay Pande? How much is that concerns about liability or other non-medical reasons?
33:09 Speaker 01 Right, you're bringing up another good point here because it's the standard of care. So that's the foundation for malpractice. It shouldn't be the standard of care. There should be a reboot, new standard of care based on intelligent partitioning of risk. So each of the cancers is a way forward to do this. We have to come up with new ways to screen that is based on risk assessment. And we don't do it, but that could be changed in a flash based on the data that exists today, which I review in the book.
33:41 Vijay Pande? Well, that's all very rational. So I just want to double click like what needs to change then? What's the process? Does guidelines have to be done differently? And what's the process and what's the body that should be doing this? And why aren't they doing it?
33:53 Speaker 01 Well, I mean, we're seeing how we can have sleeping changes without data right now. So new policies could be made. If people want to have more proof points, that can be quickly, easily garnered. But we have to have the will.
34:08 Vijay Pande? Yeah.
34:08 Speaker 01 The problem we have now is the amount of money that's being made by doing these screenings is humongous. So what is the incentive for the people that are, for example, doing the scans and the scopes and all this stuff? Do they want to change their practice? I don't know. I mean, does the American Hospital Association want to have people in their own home? So they don't have to go to the hospital? I don't think so. We have some things here that need a little adjustment.
34:37 Vijay Pande? Yeah, in any change, there's always new winners and losers and the potential new losers will fight the change.
34:43 Speaker 01 Yeah, we have a new way forward if we are willing to get it validated. And I hope we'll seize this opportunity because we may never get another one like this for a long time.
34:55 Vijay Pande? And what's different now? Is it AI or is it just the confluence of all these things?
34:58 Speaker 01 Yeah, I think it's not one without the other. Once you have these new ways to assess risk and the ways to, I would not just call it intervene, you're really going after prevention. The way you can aggressively put someone in surveillance. So with imaging now, for example, we can use AI to tell if there's inflammation in the heart arteries, even without a significant narrowing. We didn't have that before. And we can also, if we need to, do brain imaging. It's exquisitely sensitive. So we have different ways we didn't have before. And the AI part of it is, this is beyond human capability. There's just billions of data points for each person.
35:43 Speaker 01 But with the ways that the models have progressed, there's a new day using AI to promote health and health span.
35:51 Vijay Pande? So let's shift gears and talk about the future. Let's assume things work out well.
35:55 Speaker 01 Yeah.
35:56 Vijay Pande? What is the best case scenario that you think is plausible? What's the science that's coming on the horizon? Let's say we all decide to make this shift towards prevention and chronic. What do you think we will get for it in our next five to 10 years?
36:08 Speaker 01 Well, I think we'll start to see that people are eventually getting to much older ages than we are now without these three major diseases. I think that's a gradual thing. It's not like we're going to see a light switch here, but that's what we, the trend. We will see countries that will implement it because they don't have the obstacles that we have. We'll see much less of that and the shift, the bending this curve to the people that are older and healthier gradually. We're not talking about curing. We're talking about preventing. It's a lot better than curing, but it takes time to see the benefit.
36:46 Vijay Pande? That's a really deep line that prevention is better than curing.
36:49 Speaker 01 Yeah.
36:49 Vijay Pande? I think maybe for professionals involved, curing is really cool.
36:53 Speaker 01 Curing's cool, but you don't want to go there because it's much harder.
36:57 Vijay Pande? Yeah.
36:57 Speaker 01 Prevention is where it's at.
36:59 Vijay Pande? Well, some of that is then even just changing doctor incentives.
37:02 Speaker 01 Yeah.
37:03 Vijay Pande? If we can get them to be rewarded. Prevention is maybe less connected to their actions, it may seem, even though it could have such a great societal benefit.
37:13 Speaker 01 Yeah, but you know, and there are health systems that really do emphasize prevention, but they're rudimentary. Did you get your pneumococcal vaccine? Your drinking and your other social behavioral stuff? That's all types of things. They haven't worked. We're talking about a whole revamping of what we mean by going into prevent mode.
37:34 Vijay Pande? One question I love to ask our guests, I think I've asked this before, so it would be fun to get an update is, what do you do for your own health?
37:40 Speaker 01 Yeah, I've gone through some pretty major changes from the work I did to put the book together. Because I'm a cardiologist, I never really acknowledged that strength training, resistance stuff was so important, no less balance and posture. So I've totally changed that for me. I've never been this strong in my life.
38:02 Vijay Pande? Awesome.
38:02 Speaker 01 Yeah, and
38:03 Vijay Pande? How's it feel?
38:04 Speaker 01 It feels great. I mean, yeah, I just, I never paid attention to it. I used to even with patients that came in, I'd say, well, gee, you really do a lot of weightlifting here. But I was thinking to myself, well, they should be spending more time in a robe. We need both. Sleep was a big problem with me, not sleeping and particularly not getting enough deep sleep. So I got both a smartwatch and an Oura ring to track that. I wear both every night and whichever one has the highest number of minutes of deep sleep, I'm going with that, but they're usually concordant.
38:38 Vijay Pande? After you measure, how do you improve?
38:40 Speaker 01 Yeah, I had to go through a lot of changes. So I needed to get like a ritual when I'd go to bed, wake up, which I was erratic about. And I also learned about when to exercise, what to eat, not to eat, all these interactions.
38:58 Vijay Pande? When should you exercise?
38:59 Speaker 01 Well, early if I can, not too late in the afternoon, but not in the evening. And for me, the morning had a negative interaction with sleep.
39:09 Vijay Pande? Really? Exercising in the morning is bad for sleep?
39:12 Speaker 01 Yeah, I mean, I dragged all day because I do an hour, hour and a half if I can. But the morning just wasn't working for me, but late afternoon, no later than that. But also learning about whether it's alcohol, other beverages, how they affected me.
39:25 Vijay Pande? Caffeine probably.
39:26 Speaker 01 Yeah, so I, basically I've gone from a deep sleep, I've doubled it, pushing, I'm working on getting, I don't know if I'll get to triple it, but you know, it's been a steady trend and it's been really great. And it's given me more energy, more readiness and all that. Now, the other one, besides those two, I've really gone after the nutrition. So I didn't realize how much ultra-processed food I took in.
39:51 Vijay Pande? Yeah, it's so easy.
39:52 Speaker 01 Reading the labels. Now, I don't even want to have a label to read. I just stay away from it. If it has a label and it has anything more than two ingredients, anything I don't know that would be in our-
40:02 Vijay Pande? That's a really interesting point. Broccoli doesn't have a label.
40:05 Speaker 01 Yeah.
40:05 Vijay Pande? And steak doesn't have a label.
40:06 Speaker 01 No, no. I just completely bought in now because these three age-related diseases, inflammation, all of them have been associated with ultra-processed foods, a dose response even. And I have really cut that out. I mean, I couldn't relieve how much stuff I was eating that had this junk in there. I'm also really attentive to things like plastics. I don't like to see anything being stored in plastic. I don't even like to use microwave, but putting something in plastic in a microwave, that is a triple whammy.
40:39 Vijay Pande? Yeah.
40:39 Speaker 01 But we are taking in these plastics in the artery with people have a four-fold or five-fold risk of heart attacks and strokes. Once you see that study, it just is indelible. So that's another big change. I'm much more focused on these environmental burdens. But the other thing is much more inclined now to take hikes in nature.
41:02 Vijay Pande? Can you see the benefit of that?
41:04 Speaker 01 Yeah, I mean, I think that when I'm out in nature, and of course, the data I presented in the book, I always appreciated, but now I can see its effects even more impact with respect to, for example, the best sleep, surprisingly. So what I've learned, I've tried to share, I don't really speak too much or write too much about myself in the book, but all these things I'm doing, I mean, I believe in them. If I didn't believe in them, I wouldn't have written about them. And it was after culling through, there's about 1,800 references in there. So people can look at themselves and see what they think. But it's data that I've really been impressed. It's a body of evidence that ought to push us into this prevent mode, and I hope that eventually it will.
41:46 Vijay Pande? Yeah. Well, that's maybe a great place to end. I think we could follow your example. We could all be super agers.
41:51 Speaker 01 Thank you, Vijay. It's been a real pleasure.
41:56 Speaker 03 Thanks for listening to the A16Z Podcast. If you enjoyed the episode, let us know by leaving a review at ratethispodcast.com/A16Z. We've got more great conversations coming your way. See you next time.
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