How to Catch Alzheimer’s Before It Starts, with Dr. Eric Topol

21:36Dr Eric Topol:You've got all these other checkpoints of layers, and then you have multimodal AI to bring it all together. And so that's what gives us that pinpoint precision, both with respect to time, when this is going to be cropping up way in advance. And that's when we get all of these people to work with them to prevent the disease. And of course, that could be the lifestyle plus factors or it could be drugs and other means and even more high tech ways to go into surveillance. So we have a path to do this for the big three diseases. We just got to get moving on it. I want to unpack that because there's a lot there you said.

22:14I want to just ask you a question, though, before we dive into the big three, which is heart disease, cancer, and dementia. You left out diabetes. I'm wondering why you left that out. Yeah. Because it's sort of the cause of all three of those things. Well, that's right.

22:27Dr Eric Topol:Diabetes by itself, you know, we can handle that. But the problem with diabetes is it leads to the other three. The other three are the big ones we have to work with. And diabetes isn't necessarily age related. There's some of that, but it's not nearly like the other three. And it doesn't have the 20 year lead time to work with. So there's a lot of reasons why, although diabetes is considered a killer, certainly can compromise health span. It's mainly working through the other three. You know, people are not dying of diabetes, but they're dying of the heart related kidney, you know, other sequela, certainly more dementia and more cancer too.

23:07Dr Eric Topol:That's why I don't lump it in there. But I think the prototype is Alzheimer's. You saw, I wrote in the book and then also a sub stack. There's this breakthrough test, the P-Tau-217. And if you are ApoE4, I mean, if you're a carrier, that's 20, 25 % of us are carriers, or you have a family history of Alzheimer's or both, you probably want to get a P-Tau-217 because it's as good as a cerebral spinal fluid. It's as good as a pet cow scan, you know, which is a lot of radiation and hard to get. And a CT scan of the brain, but it's expensive and hard to get. Yeah. And here you've got a blood test, which is not that expensive.

23:50Dr Eric Topol:It's available in this country for the past two years. And you know, Mark, most people never heard of it. I think it's part of your function tests that you do. It is. It is. I added that. Yeah. I don't know all the tests that you do in that, but that one is a good one. So then, you know, you have if you have I don't recommend everybody getting this, but if you have APOE4 and you have family history, now, you know, with the P-Tau test and you can get a brain clock. OK, you can even get a methylation clock. You got these layers of data now. Right. And you also know about your lifestyle and what's good and what's not so good about it.

24:27Dr Eric Topol:Now you find, oh, P-Tau 217 is elevated substantially, let's say. Well, this is like an LDL cholesterol, right? Because if you exercise and you go into a healthy lifestyle, you can bring it down. And we've seen a randomized study presented here in San Diego at the Academy of Neurology annual meeting where they had these, the people who had P-tau-217 elevated. They were randomly assigned to intervention with lifestyle. And it came way down, you know, P-217, P-tau-181. all these markers, up to 75 % reduction. That should reduce the chances of ever developing Alzheimer's, particularly if it started early.

25:14Dr Eric Topol:And then, of course, if a person started late, it should put it off, it should defer it. So this is exciting, and I'm just amazed that most people don't know about this test. No, I agree. I want to just double down on that because what you're saying is so revolutionary. you know up till now basically you had a family history of alzheimer's you had to cross your fingers and you know wait around and hope to not get it and there wasn't anything we offered it for medicine that was going to prevent it or even treat it once you got it so it was kind of a scary thing and nobody wanted to know their apo e status because it's like well why should i know because right what am i going to do about it yeah and i think you know what we've learned is that now Now, with early biomarker testing, and like you said, these develop 20, 30, 40 years before you ever forget something, right?

26:05You forget your keys or you start having memory loss. You can start to see these early clues in your blood and you layer on top of that proteomics, you layer on top of that AI to uninterpret it all. And all of a sudden you have a window into where you might be headed that you could do something about. And I think trials like the finger trial and the pointer trial are these large clinical trials that show while all the drugs we have for alzheimer's have failed the lifestyle interventions can slow prevent slow and even reverse sometimes the changes that we see and i think richard isis works very exciting about about ptau 270 because it's like you can actually start to see how we can actually even reverse it once you start to have it which is a pretty crazy idea that's what's the difference where we were

26:52Dr Eric Topol:a few years ago to where we are now is that we know that these markers are so accurate and we can use them to see if we're making progress. Okay, so you have the, let's say the brain organ clock and the P-Tau 217 and someone who clearly has high risk of Alzheimer's and you go six months with this new lifestyle, right? And you see, oh, wow, the brain pace of aging is slowing down and the P-Tau 217 has come down 50%, you say, this is working. And if you want, you can do imaging, of course. But this is extraordinary because now we have the GLP-1 drugs like Ozempic, Munjaro, that are being tested in big Alzheimer's trial in thin people.

27:39Dr Eric Topol:These are not obese or overweight. These are thin people. And because they have such potency of reducing brain inflammation. So we're not talking about the drugs that are being used for Alzheimer's, which don't work very well and are very risky and can cause hemorrhage in the brain. These are drugs that have been out there, you know, 20 some years. You know, I have a whole chapter in the book is how we blew it. We thought they were only good for diabetes, you know, and it took this scientist in Denmark, Lata Knudsen, who kept pushing, we have to try it. We have to try it in obesity. And they kept saying to her, Well, it's not going to work because the diabetics only lose three or four pounds.

28:21Dr Eric Topol:Well, now we see we can get people to lose, you know, 40, 50, 60, 80 pounds. These drugs are so potent. And the reason it was blown was because the diabetics don't lose that weight. And we don't know why still today, which is such a mystery, right? But what if it works in Alzheimer's? Because it's working in so many other ways in terms of addiction, in terms of, you know, all these other cardiovascular, many conditions that we did not expect. So even if it doesn't work, there's other drugs, many other drugs that get well into the brain that knock down brain inflammation like GLP-1. And so we're going to have drugs for people who are at high risk for Alzheimer's to add to the lifestyle factors.

29:08Dr Eric Topol:But of course, you want to press on the lifestyle stuff first before you ever really start with drug.

29:24So you're someone who's saying you go get this test, you're in your 40s, shows up as something that's a little bit elevated. What do you do?

29:33Dr Eric Topol:Yeah, well, first, don't get the test unless you have the risk factors, right? I mean, you don't really want to get this without APOE4 status or at least Alzheimer's in your family. Right. Because for a polygenic risk or even that says you're high risk for Alzheimer's, something like that. Because if you get tests that are not you don't have a high test pre of the probability, as you know, you're going to get potentially false positive. And the American Alzheimer's Association, which I think has some problems, they're labeling people with P-Tau 217 as stage one Alzheimer's if it's elevated. That's not good because it could be wrong.

30:14Dr Eric Topol:Any test could be wrong, especially if it's done on the wrong people. So as long as I'm admonishing that get the test only if you have increased risk and if it's elevated, then you've got to go on a campaign to bring it down. and know, since you're saying a person's young in their 40s or 50s, they got lots of time to really get on it. And, you know, within a few years, we're going to have a lot more additional ways to bring that down. But just, I mean, the lifestyle story, it's hard to get people to adopt all these healthy behaviors, particularly get, isn't just a behavior. How do you get a lot more deep sleep, for example, a lot more sleep regularity, which has big impact.

30:57Dr Eric Topol:That's not even a behavior. That's just something that people, they have to learn how to improve. The fact when you get into this aggressive prevention mode, it's more likely that people are going to take it seriously if they have this marker aligned with their risk. So in terms of the lifestyle, that's sort of a generic term, but let's kind of break it down. Diet, exercise, sleep, stress, relationships, I mean, toxins, you call it lifestyle plus. Yeah. You know, what are the biggest levers to pull? Well, we start with a diet. You know, I think you've been on this, but the ultra processed foods are just horrendous, right?

31:36Dr Eric Topol:They are the vectors of inflammation in our body and they are propagating. They are in, I think we're talking about cause and effect of these three age related diseases. And the U.S. has the highest consumption in the world. 70 % plus. And of course, a lot of people are 80 % or more. And in the book, I review - Yeah, that's average. That's average. Yeah. Children, high, very high. And I review in the book of my friend, Chris Vontalekin, who wrote the book, Ultra Processed People. And he went on like a 30-day, and he's a really great physician scientist in the UK. And it told the whole story. He had a brain scan beforehand.

32:21Dr Eric Topol:He had all these inflammation markers beforehand. And in 30 days, kind of like supersized me, he tried to go as high as he could on ultra-processed food. By the time the 30 days was up, his brain was all inflamed. Every biomarker had gone through the ceiling of abnormality for inflammation. I mean, it was just 30 days of this bad diet. He gained 20 pounds. Now, this is something we have to work on. It's just we've done nothing in this country to bring it down. Other countries are taking it more seriously. The second thing about the diet, which I think is vital, is the protein craze. We have people out there that are advocating ridiculous amounts of protein.

33:03Dr Eric Topol:And I reviewed that in the book, that there's danger with that, not only for the kidneys, but also we've seen studies after study that show too high a protein diet, particularly animal protein can induce, promote atherosclerosis. That's the last thing we want, right? It's pro-inflammatory. So that's why, although it's probably wise if we keep up a decent amount of protein, maybe amp it up a bit as we get older, you know, maybe 1.2, 1.4 or so per kilogram, not per pound. And that's what some people are advocating. And that's just wrong. It's dangerous. there's no data to support it. You know, I talk to people who are on this protein craze and I try to get them onto the data and the evidence, which is, you know, really a danger sign if they go too high on a daily.

33:54Dr Eric Topol:And it's not going to increase their muscle mass when you go past good studies, 1.5, 1.6 per kilogram. So that's, those are a couple of the main things. I don't know what you think about that, but a couple of main things about the diet that we need to get out there. And the sugar in the starch, too, is just a component of the ultra-processed food. But I think that's part of the driver of what's causing a lot of the problem. And they're calling Alzheimer's type 3 diabetes, right? Diabetes of the brain. And I think that's a big factor for people, the amount of sugar and starch. And it's obviously hidden in the ultra-processed food.

34:27I think the protein thing is interesting. I mean, I think, were we going to say something about the sugar thing?

34:32Dr Eric Topol:I think I agree with you. I reviewed the sugar story, salt, caffeine, alcohol. I went through every one of these things. Everything you eat, fats and plant-based diets and red meat. I went through the whole thing. And you're familiar with this recent study of 105 ,000 people followed 30 years. And only 9 % of them, only 9 % got to the elderly state past age 70. And those 9%, what did they eat? They mainly plant-based foods, Mediterranean diet, some but small amounts of red meat. the kinds of things you would anticipate where the data evidence is backing it up. So yeah, the diet is really important and we keep seeing study after study reinforcing that.

35:18I think one of the things that's important, as you know, is being functional. Frailty is the killer. I mean, hip fracture is a bigger risk for death than getting a diagnosis of cancer. That muscle mass is a big deal. And the question is, that's a problem as you get older because when you lose it and it's hard to build it and there's something called anabolic resistance, meaning when you're older, it takes a lot more work and a lot more protein to do the same thing you did when you had these trophic or growth hormone-like things when you were younger, anabolic hormones that were floating around your blood.

35:50And the ProteAge group, which is a group of protein scientists led by Don Lehman and others, and I've had him on the podcast, he talks about even higher amounts being needed, like up to one and a half to two grams per kilo. and this was like I'm not a protein expert but it was interesting to read their data showing that it was overcome this resistance and the need to maintain muscle mass that their data was like the kind of global think tank on protein experts

36:21Dr Eric Topol:I reviewed all that data and I would just say if you're going to go past 1.5, 1.6 per kilogram you're starting to get to a fuzzy zone but Mark, you can increase your muscle mass not by just having adequate protein, by doing strength training. And I got into that heavy over the last year because after all the research, I always advocated aerobic exercise as a cardiologist. Cardiologist, right. And these people, patients would come in and they were really cut and buffed. And I'd say, well, what are you doing lifting all these weights, right? Well, now I'm doing that, not maybe as trying to be any like the Terminator, but I've been on a big kick on resistance and strength training, balance, posture.

37:10Dr Eric Topol:But also, I've never been this strong in my life. And I don't need crazy amounts of protein. The point being is it's part of the exercise. It isn't like you just change your diet and you build up muscle, right? It's the exercise that's so essential. And by the way, the data for resistance training, as I review in the book with various graphs, it's extraordinary for preventing age-related big three. So we should be doing that. I learned from that. I didn't realize how impressive that body of data was. Yeah, you and me both. When I was 59, I'm like, yeah, I better start strength training. And it's changed my life.

37:47And my body, I picture it with me when I'm 40. And I was a runner. I was into yoga. I wasn't overweight. but like my body looked like I was like a skinny little rail compared to now. I'm not like, you know, the Terminator or the rock, but I'm, I'm like, you know, at 65 beefier than I've ever been in my whole life. And I was like, wow, this is.

38:07Dr Eric Topol:For me, it's the same reason that's possible. I think this is a really important step. And then the other biggie is of course the deep sleep story and regularity. I mentioned it earlier. earlier, we need to get as we get older and going along, as you said, with the inflammation is that we don't get enough sleep as we get older, particularly the slow wave, deep sleep. And we've got to get that up. When I started looking at data, I was horrified because I'm not a very good. I had not been a good sleeper and I started tracking it with a ring and a smartwatch. And I'm saying, wow, I'm getting less than 15 minutes of deep sleep at night, you know, and terrible overall scores of my sleep because of that.

38:49Dr Eric Topol:And so I started finding out what is causing all this problem, right? Because I had very, you know, irregular times of going to sleep, you know, erratic. And what I ate, what I drank, when I exercised, you know, when I ate, all these factors were playing such a big role. Now I've been able to get, it's rare that I wouldn't get over 45 minutes a night, even up to an hour. So it's been a big difference. So I know that - What did you do? Oh, I did - What were the things that made a difference? Yeah, so all these things, cumulatively, by tracking, learning, like for example, not exercising too late in the day, not eating too late in the day, you know, in the evening.

39:30Dr Eric Topol:Interestingly, alcohol affects many people with respect to deep sleep, but that one didn't seem to have too much of an effect on me. Avoiding drinking too much of fluids and then avoiding having to get up, interrupted sleep made a big difference. yeah during the night because i always be hydrating you know in the evenings no don't hydrate all day long but don't hydrate in the evening so lots of things that i did but um you know the timing and also certain foods you know i was basically i wasn't aware of it but you know it's the the indigestion was interrupting sleep uh somehow so certain foods and also i think there's these interactions, you know, stress and things that we all deal with.

40:15Dr Eric Topol:I learned about better coping mechanisms to get sleep. And I still like to amp it up more because that data that I review in Super Ages, it's very impressive, the link between the deep sleep, which is when we get rid of the toxic waste metabolites in our brain. That's the time. And And by the way, I know we both see patients that take Ambien and other sleep medicine. And what's interesting is that they backfire. Not only do they not get rid of the waste, but they actually increase Ambien, especially been noted to increase the waste that stay in the brain. So the person may feel like they're getting more sleep, but they're not.

40:58Dr Eric Topol:And of course, along the way, I didn't have it. But certainly one of the concerns I had with that low amount of deep sleep was, did I have sleep apnea was at the issue. And that fortunately wasn't the case. But as you know, that's a common problem. It doesn't get diagnosed. So it sounds like writing the book helped you live longer because you learned all these things like you hadn't known before. Time will tell. But those are powerful drugs. Time will tell. I mean, strength training is a powerful drug and sleep is a powerful drug. Yes, yes. They're better than most of the drugs we have, actually.

41:29Dr Eric Topol:It did. It helped me. But of course, I wasn't going to... Once I reviewed all the evidence and I felt compelling that led me to change my ways. And I'm hoping that's going to help a lot of other people too. But I don't know if it's going to make me into the elderly. With my family history, it's always in my mind, despite our elderly trial, our study, that I may not get into yet. So far, I don't have any age-related chronic disease, and I hope I can go another 10, 20 years. We'll see. Well, I think you're a few years older than me, and if you've escaped those diseases by now, You probably kind of dodged the bullet.

42:06I hope so.

42:07Dr Eric Topol:I mean, but the main thing is I wanted to get the hard evidence out there. I wanted to get so people know that there is a huge body of evidence that is not Brian Johnson, don't die, or other longevity clinics that charge$250 ,000 that do hyperbaric chambers, plasmapheresis, all these putative anti-aging supplements, none of which have any data. you know all this kind of reckless use of things i wanted to just put it out there that hey this is what we know and it can make a world of difference and a lot of this stuff is not very expensive either you know and so that was the real purpose of doing the book and i just as a i as a um outgrowth it helped me too yeah i think the things that work the best cost the least yeah yeah eating well doesn't have to be very expensive exercising is basically free you know getting sleep and optimizing your sleep is basically free.

43:04Building relationships, connections, pretty much free. And yes, there may be things around the margin where we're going to learn in the future that maybe plasmapheresis helps, or maybe stem cells might help, or maybe some of these things that are under investigation now, like rapamycin, may help. But right now, they're edges, not the core of what people should be doing. PNC calls it majoring in the minors and minoring in the majors, And I think that's a very good way to think about it. I'm with you. You can't live a crappy lifestyle and take those drugs and things and actually think you're going to do much.

43:39No.

43:40Dr Eric Topol:And all these things that people are trying to advance, like the rapamycin story, they have a danger, too. We can't measure the immune system routinely. So why are we taking an immunosuppressant drug, which in some people could be a big deal? And if you look at this leaderboard of all the longevity researchers or influencers, they're all taking different doses. It's like a week, different dose once a day. Nobody knows, but it's never been shown to have any benefit in people. It's all in rodents. There was one trial I saw that was on an elderly, and they found that if it was given intermittently, it actually improved their response to vaccines and actually helped their immune system function better.

44:25whereas continuous dosing didn't. And I think there's mTOR1 and mTOR2, which have different roles in immunity. And so, I mean, that story's still getting unpacked, but I find it interesting. But again, it's like if you don't do the basics right, that still doesn't matter.

44:40Dr Eric Topol:Right, we don't know of any studies that are real. Those are these small studies that in a limited number of people, they're not major endpoints. But one thing that's interesting, Mark, is Steve Horvath, who came up with the Horvath clock we were talking about, that epigenetic. The only two things so far that have decreased biologic aging from that clock are exercise and then more recently the GLP-1 drugs. I mean, that's kind of interesting. That's body-wide biologic aging. Well, we haven't seen any studies that that's been accomplished through, you know, these other things like rapamycin. So I welcome, I mean, if rapamycin works or metformin or whatever, I want these things to succeed, but I don't want people to jump to that unless we have the evidence because all of these carry some risk.

45:33Dr Eric Topol:I mean, metformin carries less risk than rapamycin because it doesn't cause immunosuppression, but it isn't something that we know is going to promote healthy aging. But it does inhibit mitochondrial complex one, which worries me because with progressive of resistance training compared to placebo with and without metformin, if you did a strength training with metformin, you didn't get the same response to building muscle, which really got, like, I was like, oh boy, that's not a good thing. So yeah, there may be like... You're making a good point. You really are. This is really exciting. So basically Alzheimer's and dementia, the take-home is there's biomarkers now that we can detect early, both genetic risks combined with blood tests that give us an early indication that we should get on it.

46:18And then the getting on it part, there's a lot of things we can do, lifestyle plus all the things we talked about. And there's more for sure that we could unpack. So I want to kind of get to the other ones. Heart disease, and this is your area specialty. Yes. I want to go to heart disease, but I just want to mention

46:35Dr Eric Topol:one thing. It's kind of chasing our tails, but the environment in terms of air pollution, in terms of microplastics, nanoplastics, and also, of course, forever chemicals. These things are, you know, all three are inflammation inducers that are increasing our toll of age-related diseases, the big three, and diabetes too, for that matter. So, you know, we're not doing enough about these, and I think this is something that you've been working on for quite some time. We got to get serious about this because any advances that we're going to make, we're going to talk about cardiovascular in a moment here.

47:16Dr Eric Topol:We got to these are the things that are taking a big toll on us because, for example, the plastic story. Let's just talk about that for a second in the heart. the big study from Italy, multiple centers, where they took the carotid artery plaque at the time of surgery. And they looked to see if there was plastics, microplastics, nanoplastics in the artery plaque. And they found it in over 60 % of people. And that artery under the microscope was grossly inflamed right around where the plastics were. During follow-up. Was it a dose response? Yeah. Like, in other words, the more plastic. The more plastics, the more vicious inflammation.

47:57Dr Eric Topol:And what was even worse is the people who had the plastics followed versus those who didn't have plastics in their plaque had a four to five fold increase of heart attacks, strokes, and death compared to those without the plastic that was basically establishing residence in their arteries. And so as we talk about cardiovascular now, preventing heart disease, you know, we got to factor in that particular thing because plastics are everywhere. They're not degradable. And there were just more and more of them. We got to do something about it. But for the heart, this is where - Wait, I want to just, I want to double that.

48:37Before you get in the heart, I want to just double click on this because what you're saying, people go, yeah, toxins are bad, but to have a traditional physician who's got the credentials that you have saying that toxins are something we should pay attention to is near heresy when it comes to traditional medicine. It's something I've been talking about for decades because I've seen it. And when you look for it, you see it. Even when you look at the literature, it's been there. It's just been ignored because doctors don't know what to do about it. Because they go, okay, well, you do for exposure by doing this and that and the other thing.

49:07But this is something that I think is going to be an important thing to be investigated. How do we measure our toxic load? How do we start to help the body detoxify by supporting its both internal detoxification systems like the liver and the kidneys and the colon and the skin and sweat, all the things. How do we actually help the body detoxify? And what are novel methods of detoxification that we might want to think about when it comes to these compounds? Because they're everywhere and we're all polluted. And I think you're right. They do play a huge role in all these diseases of aging.

49:41Dr Eric Topol:You're right. I mean, the dirty air and the dirty water, the things we drink. So the plastics, of course, are pervasive. And we can do some things at an individual family level, you know, in terms of not having things stored in plastics. And like the worst case scenario is you take something, food that you have in plastic, and you put it in a microwave. It's like, oh, that's terrible. Microplastics you're going to eat, you know, to the fourth power, right? So there are some things we can do. And, you know, just to everything we can to avoid the use of plastics. But, you know, this is something we're not addressing.

50:20Dr Eric Topol:And that's where the data are so incredibly strong. And air pollution, what are we doing about air quality? Because the air quality, these fine particulate matter 2.5 and smaller, they are the real incriminating, they're the culprits for inflammation, big time increase in inflammation. And, you know, for example, we have now young people and we're going to get the cancer. I don't mean to divert it from cardiovascular because that's my true love, but the young people with cancer, why are people in their twenties and thirties presenting with colon cancer, breast cancer, and other cancers like we've never seen before?

51:04Dr Eric Topol:Who, you know, what is the, could it be the ultra processed food that they eat high amounts? Could it be these environmental toxins? Could it be, you know, the cumulative of all these things. But something has got to give there because we're not protecting our young people and we're seeing much more, a real spike in cancer. These are age-related diseases we're actually seeing in young people, which is just horrible. You know, there's literature around toxins that have been around, and even in heart disease. I remember reading a paper, I think it was the American Journal of Cardiology years ago, where they looked at anybody who had lead levels over two, which is considered normal because the level in the reference range is one to 10, but the normal level of lead is zero in the human body.

51:47It's not like it required mineral. That their risk of having a heart attack was higher or as high as those who had elevated cholesterol and an increased risk of strokes. And it was a big risk factor. And it was 39 % of the population that had a lead level over two because we live in a world where there's coal burning and lead levels in the soil and stuff from historical exposure. So you're right. I mean, this toxin story is a big rabbit hole, and I've written a lot about that, and I talk a lot about it, but I think there's a lot of ways people can reduce their risks and reduce their exposures and not be crazy, but there's ways to mitigate it and to help your body eliminate the toxins.

52:24So I agree. So let's talk about the heart prevention because people say, well, that story's been told. We've got statins. We've got this piece of SK9 inhibitors. We're all good. like what's the big deal? What should we worry about? It's just all about LDL cholesterol. What's new? What should we be looking at? What should we be thinking about? And why are we still seeing so many people with heart disease?

52:48Dr Eric Topol:Yeah, it's still the number one killer around the world, not just here. And it's still the number one killer in women who, you know, they think that it's breast cancer. No, no, this is it. This is exciting because we do know the things that we've been reviewing for risk factors, but we have a way to now establish the risk. Are they really high risk without, before they ever have heart disease, 20 years plus. And the way we do that is we can get a simple lipid panel, add the LP little a, APOB, so a little more than what is the standard lipid panel. The LP little a will be part of a lipid panel in the next year or two.

53:29Dr Eric Topol:But But anyway, when we get that lipid panel, which is, again, very inexpensive, and we can also get a polygenic risk score, very inexpensive. We can also get a heart clock, right? And we can get inflammation markers. Anyway, now you have the full stack with your records and, you know, and you have somebody who is well before they've ever manifest heart disease. And you say, oh, wow, this person is really high risk for heart disease. What do we do? Well, you get their LDL down, you know, not just to the low 70. We go down to 20 or less than 30, right? We have so many ways to do that now. We have these injectables that are against this PCSK9.

54:10Dr Eric Topol:We've got new drugs, five new LP little A drugs that are going to be out within the next year or so that are really potent. And we've had none of them, none until now. Yeah, we never had one. We always tell, too bad your LP little A is over 100, you know, nothing we can do. We're going to be able to change that. And that's going to have a big impact. We can get all the inflammation, get all over it, right? In terms of bringing the inflammation down, we've already seen how GLP-1 drugs do that before any weight loss. So that should work well in people who aren't even obese. And we've seen how that can prevent heart, preserve ejection fraction heart failure, which is half of all heart failure, right?

54:49Dr Eric Topol:GLP-1s prevent that. So for heart disease, we're seeing some really breakthroughs for the treatment, particularly the new target of LDL that we have five different drug classes, statins you've mentioned. But the PCSK9, we have three different ways to do that now. We've got other new drugs that are coming. Just recently, the CETP inhibitor worked really well on top of. So we can stamp out inflammation. The other thing is we have a metric we never had before, which is AI. And by the way, that also goes with Alzheimer's. You can do a retina AI exam. So you have a picture of the retina and you do AI on it.

55:30Dr Eric Topol:And it tells you when you're going to have Alzheimer's, if you're going to have Alzheimer's, five to seven years in advance. The retina also tells if you're going to have heart disease or a stroke in advance. It will even tell if you're going to, you know, your calcium score of your heart arteries through your retina. It's remarkable. And we should that should be widely available. It isn't yet, but it will be. We'll be doing smartphone retina check someday. Right. But here's where we get a real kick on a jump on this, because if you are concerned about high risk and somebody is, say, 40, 50, they have significant risk factors you can do a ct angio which is now becoming very inexpensive and you can look at inflammation in the artery i go through this in the book inflammation in the artery without a narrowing Okay, so basically it does AI of the fat around the artery.

56:31Dr Eric Topol:And this is something that was developed in the UK and is now getting ready for FDA approval. This is a big jump because we always were worried. So this isn't the Clearly scan, this is something else? No, no. Clearly and the other ones in the US don't do this. But this is a University of Oxford spin-out. I think it's called Carista. They're going to have that available soon. and I went through the data in the book. I mean, they've had multiple papers, but it's striking. If you have inflammation without a narrowing, it's, you know, you could have 15-fold risk of a heart attack. So that's when you use that as a metric, just like we were talking about the P-TAU 217 for Alzheimer's.

57:13Dr Eric Topol:We've got all these new things for cardiovascular. We are going to get a grip on this, and we've got to, you know, ideally start early. But, you know, the lifestyle factors work really well. This is the most preventable known of the three big age-related diseases through lifestyle. Because even without a lot of the drugs, lifestyle plays a big role. I've seen data up to 90 % by healthy diet, exercise, stress mitigation, sleep, right? Yeah. I mean, in the book, I found all these studies that I was really struck by that are recent that showed that if we practice the lifestyle factors that we've been reviewing with the details that we discussed, that gets us seven to 10 years of healthy aging without one of these age-related diseases.

58:01Dr Eric Topol:I mean, who wouldn't want seven to 10 years of healthy aging just from the stuff we've been discussing without any magic potion or pill? So that's, I think, people don't know about that. I didn't know about that. It's really impressive. That's powerful. So what you're saying is some of the advanced in cardiology are more pharmacological that you're thinking are coming like the drugs that lower this genetically determined lipoprotein called lp little a which i've been checking for 30 years apob which i've been drinking for 30 years i read some article the other day that was like there's this great new test that can be more predictive of risk of heart attack than any of their tests has just discovered i'm like what is that i'm like look click through the article it's like apob i'm like oh god yeah i mean you only need to get it once and then you can tell that if you need to check it further but you're getting at a key point here is it isn't just that we have better you know more armamentarium of drugs but we didn't know how to get the risk down you know we didn't know how to say this person's really high risk for atherosclerosis because we didn't really have we didn't use the polygenic risk score We didn't have, as we do now, we're going to have a heart clock.

59:14Dr Eric Topol:So there's a big debate out there, as you probably know, how low should we go on LDL? Should we pull out all the stops? Well, if you look at all the data, the lower you go, the more protection. But you don't want to necessarily give people, you know, ezetimibe and statin and injectable and all these things unless they really are at high risk. Then you go for broke and you also get the LPA and you get the inflammation down. We have ways that we can do that and we're going to keep having better ways. So this is a striking, it's a combination of who's at risk, the partitioning of risk and having a better ways to work on that risk.

59:52Just to play devil's advocate, because this conversation comes up all the time. You're a cardiologist, so your favorite organ is the heart. And so your idea is get the LDL as low as you can. Not every day. Your brain is made up of a lot of... Only in people who are at high risk. And people are at high risk. Okay, so if you're at really high risk. But what about the effects, for example, on the brain and cognitive function? Because cholesterol is a big part of your brain. And sex hormones, which is what your testosterone is made from, is cholesterol. So how do you kind of navigate that? And what's the truth, and what do we know?

1:00:22Dr Eric Topol:Yeah, I mean, the statins are probably the most studied drug class in history, really. some of the data that comes out of these big meta-analyses which say oh people don't get any leg cramps that's not true you and i know that's not true people do get severe leg cramps where they can't even sleep at night you know uh and and all sorts of other you know leg uh and muscle related symptoms now with respect to cognitive and uh sexual dysfunction the data really don't show a hit there at all. And in fact, you know, I think that we have some data to suggest the chances of having dementia in people. And Alzheimer's, as you know, accounts for 70 % of dementia.

1:01:14Dr Eric Topol:That if you don't have the LDL lowered to, let's say, less than 100, less than 70, you're going to be at higher risk for dementia. So if anything, the data support statins. and you know the data for sexual dysfunction it's again some of that's vascular and it if it's vascular we're talking about atherosclerotic uh and that again is going to be uh ameliorated with and of course we don't have to just rely on statins a lot of people do have side effects from statins no matter what the group at oxford keeps saying that everyone can take a statin and And it's just, you know, it's mental if they can't.

1:01:54Dr Eric Topol:When I wrote an op-ed in the New York Times like a decade ago, and I called out the diabetes from statins, okay, because if you take a very potent statin, you have a higher risk of developing type 2 diabetes, right? Oh, did I get slammed by my cardiology colleagues for that? I said, well, wait a minute. That's the data, folks. I'm sorry. And over the years, we've seen many more reports about, you know, the potent statins, high doses where you get a higher risk. And you know what? Most physicians are not keeping up with this. They're not watching their patients to see if their glucose, like ohemoglobin, you know, A1C or fasting glucose.

1:02:33Dr Eric Topol:And this is bothersome to me because that is a side effect of statins, particularly potent statins. So again, this is important because if we're going to lower LDL and pull out all the stops and, you know, high doses of resuvastatin Crestor or atorvastatin Lipitor, that could also raise the risk of that person developing type 2 diabetes. We don't want to do that. And we have cardiologists, my colleagues, they are really sold on statins and they basically ignore this diabetes issue. And did I ever take grief? No. I agree with you. And I think there's a concern I have around its effect on mitochondrial function and some of the data I've seen that even in people without muscle pain, even without elevated muscle enzymes, that there's mitochondrial damage on muscle biopsies.

1:03:24And for me, mitochondria are so key to healthy aging in the brain, in everything from Parkinson's to heart disease, diabetes. Diabetics have poorly functioning mitochondria. That may be part of why it causes it. And so I'm wondering, you know, some of these other drugs that are coming down the pike, even though some of them are expensive may be a better solution well people that have a clear-cut

1:03:49Dr Eric Topol:adverse effects um you know the the pcsk9 injectable drugs are a winner because they're potent and they have not been associated with diabetes which is really interesting they have not been associated with cognitive uh or other side effects so most insurers cover that now. We went through years where it was because they were so expensive, the cost has come down. So as long as people have the right indication where they have significant side effects or they need to have their LDL substantially lowered, it's usually not a financial stress for most people. So heart Z is still its lifestyle, but then there's a cocktail of other drugs in very high risk patients that you can detect early to figure out.

1:04:32And what about lipoprotein fractionation, which is a lab test that we include as part of Function Health, as well as APO-B and LPA, something I've been testing for 30 years. But do you think that's as important? Because to me, the particle number and particle size story is important. And it's a sort of a clue that there's insulin resistance, which is one of the biggest drivers of heart disease and all the other age-related diseases.

1:04:54Dr Eric Topol:Yeah. I mean, I think it's mild, potentially mild incremental information. I just don't see that it has nearly the impact of just zeroing in on LDL and LP little a. And I do recommend that everybody get an ApoB at least once. And then you can figure out whether that needs to be further assessed. These other things, you know, it's an additional expense. I just haven't seen the value. But, you know, I have colleagues that are lipidologists that test every known particle in the mankind, right? I just haven't. I haven't really seen the benefit because it doesn't change usually. to me, I got to know the person's risk.

1:05:34Dr Eric Topol:And then I'm going to go after inflammation. I'm going to work on their lifestyle and if necessary, you know, get their LDL down as low as possible. So the other things just don't have a, for me, a added value. But I do know there are people that are, you know, wild and crazy on every particle, small, large, dense, you know, you name it, out there. Yeah. Yeah. So I hear you on that. I think it's, you know, sometimes more information isn't always better but you know what is the most important information i think you cover that in your book and i think you know we're going down the kind of the horseman of the apocalypse you know the uh the the heart disease the cancer the dementia i think diabetes is sort of all in there related but you're talking about how there's kind of a newer with the advances in our diagnostics whether it's imaging or retinal scans or new new ways we can measure dementia biomarkers we never had before cancer we'll get into in a sec that these diseases can become more optional like they're not inevitable they have more agency than we ever had before given what we know now and when you layer off what we're learning with a ai and using multimodal treatments we'll be able to actually make a big dent if people really understood how to navigate this and the sad part is that you know you spend your time thinking about what's coming, most physicians are just trying to deal with the onslaught of what is and don't have the bandwidth to actually apply this stuff until it kind of is way often decades later.

1:07:06And so I really appreciate your sort of paying attention to what's happening and keeping your nose to the scent of where things are emerging because otherwise people just don't know. And doctors, like you said, don't know. And the average person doesn't know, but this is such a hopeful message i i want to kind of finish on on cancer because i think you got this is one of those things that you know the c word you know nobody wants to get that diagnosis it's very scary um most cancers are picked up late stage um when this five-year survival rates are very low in the five to twenty percent if that and picking things up early and understanding your risk can can lead to cures essentially like and i think with what i'd like to hear is your sort of perspective on this with new uh liquid biopsy testing with with new new technologies of imaging with new um you know um maybe other proteomics that are coming what what is what is out there that's emerging because you know my sister died of cancer in 57 my dad died of cancer he was otherwise really healthy, he'd been a smoker when he was younger, but quit and ended up getting lung cancer.

1:08:23They could potentially even still be around if they hadn't died of cancer. And I don't want to get cancer.

1:08:29Dr Eric Topol:I'm with you. Yeah, my mother died of cancer in her 50s. And most of my road is on my father's side, had colon cancer. I've had a lot of cancer in the family for sure. And I agree, no one wants to go through this and i do believe we have a path to prevent cancer um and certainly it's spread right uh if you can find it microscopically which we don't right now very well um long before it's ever shown on a scan and once it's on a scan if it's really cancer you're talking about billions of cells right you want to find it if it does exist microscopically so So why is this such an exciting area? Again, we can find through a full stack who's at risk and for which cancer.

1:09:15Dr Eric Topol:And so we have a way, you know, whether it's polygenic risk or genome sequence, we can do, for example, you know, just looking at the clocks, which is another way to get a window into a risk of cancer. If a person has a significant risk, and, you know, family history is part of that, right? Then they also confirm through these other, I mean, a simple polygenic risk will tell us a lot. This is now a different story completely, Mark, than the way we screen for cancer today, which is as dumb as it could possibly be. Age 50, you show up. Women, mammogram, right? All right. Only 12 % of women in their lifetime will ever have breast cancer.

1:09:57Dr Eric Topol:88 % will never develop breast cancer, but they're all supposed to get mammography on a frequent periodic basis, starting age 40, 45. This is crazy. We don't do anything to partition risk. The same for prostate cancer, colon cancer, you name the cancer, this is what we do. We treat every human the same. We waste all this money on mass screening, right? Now, what I'm suggesting is let's partition people's risk. If they're high risk, then they should have screening. But that screening is different. It's basically establishing the risk. And then if we see a person, you know, as a significant risk, you can then do a plasma tumor DNA assessment, right?

1:10:46Dr Eric Topol:That right now is pretty expensive. It's$800,$900. The one that's used the most is Gallery of Grail. And almost 400 ,000 people have had that test. But guess what, Mark? The people who've had the test is because they're age 50. I mean, that's a plus. That's not the reason they should get the test. It should be because they have risk of cancer. Anyway, the yield for that test is very low. And most of it is already late stage. Two out of 1 ,000, you might pick up an early cancer. So you got to use the test right and the right people. This is something I can't emphasize. then that test and all the other liquid biopsies have a much better chance to be helpful.

1:11:29Dr Eric Topol:So we have that. But also, this is where our immune system kicks in, because we don't have that immune metric, system metric, except for immune clock. But if we did, you know, if our immune system was amped up, we wouldn't have cancer spread. We wouldn't see metastasis. It was surveilling, yeah. You know, what we know is this. Some people, this is really fascinating. Some people will have a positive test for tumor DNA and they reassessed in a few months and it goes away. What do you think happened? Was it a false positive or did that person's immune system kick in? I think what we're learning is it's the immune system.

1:12:09Dr Eric Topol:And what we have to get is this is the missing piece right now, the immunome. If we can get this and find people who are at risk for cancer and just make sure throughout their lifetime that their immune system has got good integrity and it can fight off the threat of a cancer, of a foreign protein that would be on the antigen, on the surface of a cancer cell. So I am really gung ho because if you look at the treatment of cancer, we're now seeing things we've never seen. Personalized new antigen vaccines to cure pancreatic cancer, to cure renal cell carcinoma, intractable that is people that fail everything else.

1:12:50Dr Eric Topol:The other thing just to mention here again is AI. We are seeing AI used for the electronic health record using the unstructured nodes and the regular nodes and set points. That is the lab values. But even when they're in their normal range, AI analyzes, whoa, it's even in the normal range. And we look at it, say there's no asterisk, so it's OK. Well, no, this is flagging a risk of pancreatic cancer. This is flagging your risk of ovarian cancer. The hardest diagnosis of cancer we're seeing that can be brought much earlier through AI of all of a person's data. We saw it from the study that was done in Denmark in the VA for pancreatic cancer.

1:13:35Dr Eric Topol:We're going to see Sloan-Kettering has - But what were they looking at? Because they weren't looking at tumor markers, were they? Were they looking at just regular blood tests? Yeah, so they looked at a person's nonspecific symptoms, like abdominal symptoms for pancreatic cancer, and they saw ranges of liver function tests in the normal range, but trending in the wrong direction, right? So the AI picked up the higher risk of people that we might discount these are nonspecific symptoms. These tests are lab tests. They look normal, but they're not normal when you are looking at this in serial assessment.

1:14:11Dr Eric Topol:So I'm also, lots of different ways that AI is helping us to gauge a person's risk and help us to pick up these occult, difficult to diagnose cancer. I mean, this is so important what you're saying, that there was a paper in Nature Medicine recently on personalized lab data. And the idea was that exactly what you're saying, that even though it's, quote, normal, it may not be normal for you. Because if you were, like, 20 and it goes up to 35, which is still in the normal range, that might not be good. That's right. And we need to start getting a baseline of what our data is and tracking it over time and having AI help us learn from it.

1:14:52because you know as a doctor you see thousands of patients that come in and you know they've had their lab panel every year you can't keep in your mind what their liver function tests were last year or five years ago or 10 years ago and how that differs and how that what's the variation from their normal or baseline test you can't you can't do that as a human being right and i mean i have certain patients who are ocd and they bring in spreadsheets with years and years of their data and you can graph it all and you're like wow that's like i never saw that before but without Without that, you really don't know what's going on.

1:15:24Dr Eric Topol:That's the paper I was talking about on set points. Exactly. Yeah. And we just don't look at that because if it's normal, we don't look at the last few years, how things are just inching up. And that's the way AI can help us. And it is helping. We've already seen proof of it. So for a variety of conditions, but especially these three age-related disease and especially cancer, because we are not doing well with cancer. You said it. We're only diagnosing cancer when it's way too late. And that's got to change because when it's picked up, first picking up that the person has risk and picking up when it's microscopic, well before you ever catch it on a scan.

1:16:07Dr Eric Topol:again that's why you know i'm not i'm not keen on these you know total body mris because they're being used to pick up already a cancer that's got a mass right and of course a lot of times it's not even cancer it's benign and people go through unnecessary biopsies but i do think if a person's high risk and certainly if they have a positive uh liquid biopsy you know tumor dna then it's a very reasonable thing to pursue we're going to do much better and all these years of trying to treat cancer and cure it. You know, what do people have to go through to get there when you could prevent it? And, you know, I think this is where we have a brilliant future.

1:16:46Dr Eric Topol:It may take a while to get it implemented, but it's ready to go in many respects. Just to go a layer deeper. So just, you talk about polygenic risk for cancer and we've heard about the BRCA gene or, you know, familial polyp disease, increased risk of cancer disease. Those are unusual, although they're the things you can measure and track if you have a family history. You're talking about a different set of genetic biomarkers that are being discovered that help us segment people in terms of their risk. Right. To different cancers. Yeah, so you're bringing up the rare mutations. But, for example, they can all be had in a sequence which costs a couple hundred dollars, a full genome sequence.

1:17:27Dr Eric Topol:And BRCA2, we as men, you know, a lot of us carrying a BRCA gene just because we don't have breast cancer. You know, that means we have a higher risk of prostate cancer ourselves and other forms of cancer. So, you know, these these are pathogenic genes. And I go through that bracket two story in some depth because of the Icelandic data where it made a difference of up to seven years of healthy aging, mainly because of cancer. Now, so you get these rare so-called pathogenic genes that have a high risk of cancer. But you also can get a whole bunch of susceptibility genes. So they're not this high deterministic, you know, very like we were talking about, APOE4, two copies.

1:18:14Dr Eric Topol:But they are increasing the risk. So what you have are three different types of gene markers. One is the rare variants like BRCA2, BRCA2, and as you said, Lynch syndrome and these other familial polyposis. The next is the common variant. The common variants, which is what you pick up in a, these are like, say, 200, 300 gene variants that would give you the high risk for breast cancer. They're not BRCA. These are just common variants that you got to add mixture from your mother and father, right? And then the third group are these other susceptibility genes that can be gleaned from a genome sequence.

1:18:54Dr Eric Topol:When you have all that data, which is, again, not expensive and processed properly, then you know what type of cancer you're at risk for, if you're at risk for a cancer. It doesn't tell you when. It just says yes, no, right? The when is when we have to get on this early and not treat everybody who's 50 and older as if they were a cattle, that we're all the same. We have to be much smarter about this. This is what we call precision medicine or personalized medicine. And then we're finally entering the air. I think AI is going to help us get smarter about that. The other thing you sort of mentioned was sort of liquid biopsies.

1:19:39And you kind of touched on this a little bit, but proteomic kind of testing. The liquid biopsy, from what I hear you saying, you don't think it's a good screening tool because it picks the things late. But if everybody got it, it would pick up things earlier, right? If it was sort of cost was down and scale was up for blood tests every year with your checkup, you could potentially be picking up stuff much more frequently and much earlier, right?

1:20:07Dr Eric Topol:Well, potentially, but you see, it's just being done on the age criteria. And the yield of picking up an early cancer is two per thousand people, which is really, really low, right? that doesn't make it unless you're one of those two yeah i mean and also you know uh if you have the test and it's negative that doesn't put you in you know in a safe zero risk group yeah it's only if it's positive where it's really helpful i do think these tests are going to get better there's lots of ways you know this is a very minimal amount of tumor dna in the plasma and there's ways to jack that up to make the test better and as you got to it's got to be cheaper um but yeah again this whole base or theorem of don't do tests that are not in people who are healthy of no risk but when you do it in people like the two per thousand i cited is in healthy people age 50 plus but if it was done in people who were you know clearly had increased risk that yield of picking up then it's a better test oh yeah and also when you're paying 900 uh that's substantial, if we get that test down to$100 or something like that, and it's more sensitive, more accurate in the right people, it's going to become very commonly used.

1:21:29Dr Eric Topol:So you're heading down the right path with that point. Yeah. And then the other thing I've been hearing about is proteomic tests, where some of the common proteins we look at for cancer, like CA-125 or CA-99 for colon cancer, like they're combining that with multiple other proteins and they're able to kind of using AI to predict that you're, you know, you'll be able to pick up these cancers much earlier with these proteomic signatures that they have in the blood, which are really inexpensive to do. Right. So that's a Johns Hopkins, Burt Vogelstein effort. And that's right. As you said, they combine some key proteins that have been established as markers with some gene variants and made a relatively inexpensive test.

1:22:13Dr Eric Topol:And that's one that certainly has a potential as well. We're going to be able to do so much better with the screening using, you know, the blood. Because once it shows up in the blood in a microscopic, that's when we, you know, get all over it. Because this is, I think, a new era of early diagnosis. It's essential. And we just, you know, again, you get it on a mammogram, it's already got a problem, you know. And we're not even using AI in this country for mammograms routinely, and we should. That's the best AI case that exists today. 100 ,000 plus women in Sweden. The AI picked up 25 % more cancers compared to radiologists alone.

1:22:55Dr Eric Topol:You know, significant cancers. And no increase in false positives. Why aren't we using that? So we're not doing a good job here for cancer screening or partitioning risk. No less of preventing it. I mean, you mentioned imaging a little bit, but my understanding is that with new AI advanced sort of interpretation and stuff, that with these more high-resolution scans, you can pick up cancers down to two millimeters, which is pretty small, like basically the sign of a ballpoint pen. And at that point, they're not likely to have spread or metastasized. And then, you know, you can see changes over time if you do serial imaging.

1:23:36It seems to me that's kind of a useful tool. Might be. And it may pick up things that are more sensitive than the gallery, which is not as sensitive.

1:23:44Dr Eric Topol:Yeah, it might be. I think what we've seen, at least unequivocal, a huge trial, is that AI of a regular mammogram, not like you're talking about, not ultra high resolution, it can really make a difference. And so that I think is, you know, we should be implementing that and we're not. And it's just, you know, we're missed opportunity. There's a big study that showed that if you have AI analysis of a regular mammogram, you can predict cancer from that in that woman five years ahead if they're going to develop cancer. So the AI of scans continues to see things that we humans can't see. and the fact that you can look at a mammogram with an ai not only make the diagnosis of cancer more uh you know better than radiologists alone but also see some patterns that indicate the person's much higher likelihood of cancer in the next five years so it's just like what we're talking for about with the ability to predict the other age-related diseases yeah so the and the fourth thing you said was really around finding ways to enhance our own body's immune function Yeah, yeah.

1:24:55Like natural killer cell function. I know Patrick Soon-Shang is working a lot on this, and I don't know, I'm not deep enough into it to know whether there's a lot there to it, but it seems like an interesting theory that if we can see a decrease in our own tumor surveillance with lower natural killer cells, which is part of our immune system, the white blood cells that kill cancer infections, that we could amplify that effect, that could be a powerful therapy.

1:25:21Dr Eric Topol:Yeah, so this, there's a whole chapter on the immune system, And, you know, after the brain, this is the most complex system there is. There's so many different cells and, you know, interferons and antibodies. But the big thing here is we have ability to control our immune system like never before, up or down, like a rheostat, right? And with that capability, that gives the confidence that we can amp it up for people at high risk for cancer or the earliest possible diagnosis. So we're no longer going to give these toxic drugs, but we're going to just get their immune system in high gear. And also, of course, what we've never seen before, Mark, is by taking people with autoimmune diseases like lupus, systemic sclerosis, even multiple sclerosis, by giving them T cell, engineered T cells, CAR T, directed towards depleting their B cells, that when the B cells come back, they forgot that the person has an autoimmune disease.

1:26:25Dr Eric Topol:They have a control alt delete. I mean, this is incredible, right? That they no longer, and for now three, seven years of follow-up, they're cured of an autoimmune disease. We had never seen anything like that before. And of course, we're seeing more and more reports of this ability to cure, you know, really vicious autoimmune diseases that can, you know, killers and no less really severe morbidity. So that is another, besides the cancer immunotherapy, which is huge. Oh, I mean, you, the fact that we can, the more you give an immunotherapy, a higher gear high, the more chance you are going to be able to treat successfully a person with an intractable cancer.

1:27:07Dr Eric Topol:So between all these things, we're learning about the immune system, no less the missing metric, the ability to test a person's immune system at any point during, let's say, their annual checkup or whatever. Once we get that, that's the missing link right now. And then we're also - That's the protein clock. That's the immune age protein clock. Yeah. Yeah. We have an immune clock, but we want more than that because that, as you got to early on in our conversation, that's a piece of it. But we want to know about the T cell story, the B cells, the NK, all these different cells. We want to know about, I do present in the book, a kind of first tier immunom that I had of a Johns Hopkins startup called Infinity Bio, where I had all my auto antibodies, every virus I've ever been exposed to in my life.

1:28:02Dr Eric Topol:Interestingly, I never had been exposed to CMV and all sorts of things that are going to help. And this can be done inexpensively. It will be common. It's all part of this immunom that we don't have right now that we need. To loop back on the cancer thing, but before I go on that, you mentioned T-cells and B-cells. People probably don't know about it. B-cells are the ones that create antibodies. And autoimmune diseases are where you make antibodies against your own body's tissues. So that's why it's so important. And T-cells are more of an ancient part of your immune system. They're more general.

1:28:31and and and are we call cell mediated which is different than antibody mediated and those will basically turn off the b cells so that you don't make antibodies that's kind of cool i didn't know

1:28:42Dr Eric Topol:about that yeah you know these t regs that are the key t cells that you can you know get to tone down um your whole immune system and then you know you and then killing this these cells that have the the foreign, the alien antigen, the cytotoxic CD8 T cells. I mean, so the immune system we have is rich. The problem is, as we get older, you know, it lets down. And some people more than others. And we have to be on top of that. That's the one thing that if you had to go back and say, the elderly, how did they get there? Maybe some of them are just, you know, random stochastic luck. but for the most part these people are uh you know they got a great immune system that just carry them through and we want everybody to have a great immune system someday good and i think we're going to learn more about how to do that just to kind of go back to the cancer story i just want to finish summarizing it because as i think about all these new technologies whether it's you know collections of genes that put you at higher risk that aren't a cancer gene but that you know collectively increase your risk combining with the liquid biopsies to get more and more accurate at less of a cost combined with protein signatures of different cancers that can be picked up, you know, way before you'll see anything in any other test combined with better resolution, AI imaging done serial over time.

1:30:05It seems to me that, you know, you can't prevent us from getting cancer because we live in a toxic world and there's shit that happens, but we could make dying of cancer a historical footnote. Oh yeah.

1:30:18Dr Eric Topol:Yeah. Is that fair to say? Yeah. I mean, what we have to do, and I go through this in the cancer chapter in the book, we have to prevent metastasis because people don't die of the cancer per se. They die of the spread of that cancer. And if we can just get rid of metastasis, which we can, there's a way to do this now, then that's going to be our big dent in the cancer story. And, you know, obviously we want to even catch it when it's before it gets to microscopics. And we put people under surveillance who once we determine they're at high risk. But I think what is so exciting here is just prevent it ever getting legs.

1:31:00Dr Eric Topol:If it doesn't spread, we got a winner strategy here. You and I can geek out on this all day long. I think we didn't get to a lot of things I didn't want to talk about, but we covered, I think, some of the most important things, which is the advances in medicine are happening so rapidly that we're learning about ways to detect early, very early, far early than we used to, and to be proactive with what we learn about through lifestyle and other novel therapies, that we can make these three horsemen of the apocalypse kind of not so scary anymore, heart disease, cancer, and dementia. Yeah. I mean, that's the nuts of it.

1:31:38Dr Eric Topol:I think what's so exciting and why I'm so optimistic is for millennia, we talk about preventing these diseases. And we never did. And now we can do it. We can do it. It wouldn't happen if we didn't have the science of aging metrics we've been discussing, these new ways to track a person really accurately and temporally. And it wouldn't happen without the multimodal AI to assemble, integrate all the data at the individual level. So it's these two things coming together that's made this possible. It's a unique, really momentous time. And that's why I'm so optimistic that we can make a difference.

1:32:19Dr Eric Topol:This will be the chance in medicine to finally fulfill that fantasy of primary prevention. And really, at the end of the day, it comes down to creating large data sets on each individual. so learning about all your biomarkers and data from genetics to proteins to lab testing to be able to understand the root causes and the risks, and then using AI and big data analytics to actually make sense at all through the lens of our new understandings of human biology and systems biology. And to me, that's, to me, so exciting because we've been sort of just playing reactive medicine for so long. And this is a time when we can move towards more proactive medicine.

1:33:10And I think doctors would be happy about that. If we can figure out a way to make them do their job in a more sort of streamlined, easy way that makes this accessible to them and to their patients, it's going to be a game changer.

1:33:25Dr Eric Topol:Yeah, I mean, you know, we've been banking on cures, and that's much harder than prevention. Yeah. And, you know, this is a winning plan. If we get serious about it, we can really do something. Well, that's exciting. I think everybody needs to check out your book, Super Agers. It's quite a story. It's a little more sort of technical than maybe most people would like, but there's Chachi Boutique and look up stuff you don't understand. And I think that this book is a potential way to change our thinking in medicine. I really enjoyed it. And I'm really grateful for you being so curious. You're like a curious George.

1:34:05And I think, thank you for your curiosity. Thank you for all the work you've done in medicine for so many years. And hope we get to chat again soon and get you back on the podcast and be talking about some things we could talk about.

1:34:16Dr Eric Topol:I would just add, I tried to get it as simple as I could for everyone to understand. And there are some parts that get a little dense. I apologize early in the book for that. But I think there's a lot of things in there that hopefully everyone can understand. And I did do the reading so that people, they don't have to, you know, read it. They can just do the audio, hear the passion and all that. And finally, there's 70 some graphs in there. So a lot of times people can grasp the graphs. And so hopefully your point is a good one because there's a lot of 1 ,800 citations. So there's a lot there.

1:34:54Dr Eric Topol:Hopefully the people will get something out of it. I know I'm going to see you well over 100 years old. I hope you're right. And vice versa. If you get to 100, invite me to your birthday. I just want to get to whenever age and say as long as I can to meet that kind of worldly criteria of plus 80 plus and no age-related major diseases that we've been discussing. I think that's a take-home. Don't end up being elderly. You can be elderly by just following this advice. We're going to get there. A lot more elderly in the future. That's what's in store. Thank you. All right. Well, thanks so much, Eric.

1:35:30Thank you. If you love this podcast, please share it with someone else you think would also enjoy it. You can find me on all social media channels at Dr. Mark Hyman. Please reach out. I'd love to hear your comments and questions. Don't forget to rate, review, and subscribe to The Dr. Hyman Show wherever you get your podcasts. And don't forget to check out my YouTube channel at Dr. Mark Hyman for video versions of this podcast and more. Thank you so much again for tuning in. We'll see you next time on The Dr. Hyman Show. This podcast is separate from my clinical practice at the Ultra Wellness Center, my work at Cleveland Clinic, and Function Health, where I am Chief Medical Officer.

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