B (3:59)

It is over.

A (4:01)

Dr. Topol, thank you so much for coming on on.

B (4:04)

Great to be with you, Kara.

A (4:06)

So in your latest book, Superagers, you write that we're at a unique moment in medicine where we've seen a quote, historic convergence of breakthroughs, end quote. Particularly around anti aging. After a year of reporting on this is exactly the conclusion I came to, except a lot of it is being masked by a lot of nonsense at the same time, which probably happened the last time we had this happen. But briefly walk us through the most significant breakthroughs and explain how they've converged. Because this moment in anti aging science is different than where we were 10 to 15 years ago.

B (4:38)

Exactly. It is really a turning point. The science of aging is where we've made these big strides. So there's a lot of noise out there, as you well know, but the signal is that we can quantify aging and understand the biology much better. So for example, we now have these organ clocks so that within our body we can tell if our brain is aging differently than our immune system and our heart and arteries and whatnot. So we didn't have anything like that before. And so we we also understand that inflammation, so called inflammaging, and immunosenescence, the immune system are big drivers of age related diseases. So while so many are working on reversing aging, Kara, the real opportunity here is actually accept that we're going to age. But let's squash the age related diseases since so much understanding has been enhanced.

A (5:36)

You know, you talked about immunosenescence, talk about each of the parts you just talked about. It's essentially knowing how to fix age related things on parts. Correct? Or is that kind of too idiotic way of saying?

B (5:49)

Right, right. We used to think that everything was genetically driven about healthspan and lifespan. But.

A (5:55)

And it is in part for people

B (5:57)

to understand, it is in part, but less than, particularly health span, less than had been previously.

A (6:05)

So in the book, you introduce the concept, which I think is an important one, of healthspan versus lifespan. The goal is to max out our total number of healthy years of life as opposed to solely focusing on longevity.

B (6:15)

Yeah. So when we looked at, for example, 1400 people who were almost 90 and never been sick on no medications, and we looked at their whole genome sequence, you know, we didn't find very much to account for that. But the immune system seems to be the real explanation for many of these people reaching such advanced age that their immune system has very high integrity, it hasn't lost its protection against cancer, and it also isn't hyperactive, for example, in the artery wall for atherosclerosis or in the brain to promote reaction to these misfolded proteins. So the three big diseases of aging, neurodegenerative cancers and cardiovascular. The common thread is that we need an intact immune system because if we don't, then we start to see this process of inflammation get unleashed. And when that happens, you know, then these diseases go into an accelerated phase. So even though they take 20 years or more to incubate in our bodies, our immune system keeps us healthy. And there's many things, of course, that we can do to promote that, and we gotta do even more things in the future. But that's been the biggest breakthrough to understand that the brain, which is the master command central for the immune system, and the brain and the immune system together are largely accounting for this remarkable health span that we've seen in people.

A (7:45)

Now, when you talk about significant breakthroughs, there's a couple. One of them, of course, everyone always asks me and I'm like, well, friends and family are actually much more important than you think, scientifically and personally. I said, but one of the things is don't be poor and don't be under stress. Right. And I don't mean stress as like your husband was mad at you or something, you know, or whatever, you got in a fight with your kids or whatever. It was something else. It was sort of this idea of don't be in situations that stress the immune system in that regard, whether it's by food or by sleep. And I was interviewing one of these billionaires and he goes, well, if people just slept more, you know. And I was like, well, some people can't because they're poor, you know what I mean? Which is interesting. So maybe stack rank them a little bit for me.

B (8:26)

Yeah, I think what's going to be the biggest, what we start to see now is that AI is going to make, I think its singular biggest contribution over the years is that it can have remarkable accuracy and prediction 20 years ahead, which leads to prevention of cancers which now at best, we can detect when they're already cancer. But we're talking now about prevention. The same for Alzheimer's. I mean, we're starting an Alzheimer's trial later this month to prevent the disease. We've never even thought about that before. And also for cardiovascular. So the fact that we have these markers of aging that we can track the immune system and inflammation and we have AI to pull all the layers of data for each person, this enables prevention. So that's the future. Everybody's talked about AI and health, but I think that ultimately, of course, not yet, but ultimately it'll turn out to be its singular most important contribution. But otherwise, for example, the biggest breakthrough in neuroscience in decades has been a marker for Alzheimer's disease, pTau217, which tells us even two decades ahead that someone is really at high risk. And it can be modified by exercise and lifestyle improvements and hopefully medications. The GLP1 drugs have outperformed any expectations and they have become realistically the most potent way to knock down inflammation in the brain and throughout the body that we know, the safest and most potent. So it has diverse potential to even help us ultimately to prevent these diseases,

A (10:17)

which require more and more study about how as it moves into the population, which it is at a rapid pace.

B (10:23)

Absolutely. You know, we've seen it have these weight loss independent effects in heart disease, liver, kidney and even arthritis, osteoarthritis, psoriatic arthritis. But whether it's gonna pan out as a prevention for Alzheimer's disease and prevention of these other age related diseases to be the first extending healthspan drug that is obviously has to be proven. That's gonna take some years ahead.

A (10:50)

So giving the advances in anti aging medicine, talk about this idea of a health span, because I think what people don't realize is most people spend most of their money in sick care, like not healthcare at the last many years of their lives. So talk about someone who's healthy at 70. What does that mean? What is the realistic health span in 2026 in certain countries? I've visited Korea because the women there are showing remarkable health spans, which is for lots of different reasons, but they're studying it now. But talk a little bit about what that means. A realistic health span.

B (11:22)

Yeah. So the average American has already one of these age related chronic diseases by 64. So that's the end of their health span. Whereas the average American has a life expectancy lifespan of 79. So there's a 15 year gap among Americans on average. Of course, many Americans by 64 have multiple chronic diseases. But that 15 year gap is difference between health span and lifespan. And that's why when I saw Kara Swisher wants to live forever, I said, well you gotta add when I'm completely healthy, if I'm completely healthy.

A (12:03)

I think you get the joke. How ridiculous.

B (12:04)

Yeah, no, no, I do. But you know, lifespan, you know, we can keep someone alive on life support forever, but what kind of life is that? So what we really want is to extend healthspan. And you know, I think we're on the brink of that. And that's what's exciting is that preventing age related diseases will get us that extension of healthspan. We want to close that gap that when people are 80, that they lived most of their life healthily standing up.

A (12:31)

Right. I mean, Ezek Emanuel, who I interviewed in the show talked about that. He goes, if you had to spend the last 15 years of your life in a wheelchair, debilitated, that's not life. Essentially something else. So you say there's a lot of hype around anti aging, which you say is misplaced and not aligned with evidence in people. I couldn't agree more. You criticize the longevity Lifespan Circus, the carnival barker scientists who make, and I'm quoting you make false claims in Hawke supplements. Talk about what this is and who are some of the ringleaders of this longevity lifespan circus. I have worse words for them, but circus works. Grifters is the word I use.

B (13:05)

Grifters, right, grifters. This is deep. There's so many influencers who have such big impact and they're selling, they're selling supplements, expensive supplements like AG1 and claiming, you know, these anti aging properties that have never been proven. They're also now pushing peptides really heavily, none of which have any data. And they have all sorts of other antics, but of course they're always admixed with some truth. So it's hard for the public to separate that out. And we have longevity clinics, even at, you know, prestigious institutions that are promoting this idea that we can keep your, you pay us enough money and we can keep you with extending your lifespan. You know, so it's all over the place. We even have our HHS secretary as part of this because he's promoting peptides. We have people like, you know, Peter Attia, one of the biggest influencers promoting rapamycin, which has no proof in people. Cold plunges, protein out of control, Amount

A (14:08)

of protein out of control. You wrote a great column about that.

B (14:11)

You know, Andrew Uberman is another key force of supplements. But I always tell people if you really want to have somebody you can rely on the first step is that they're not selling something if they're already hawking something or, you know, whether it's protein bars or supplements or something anti aging. Because we don't have anything anti aging, okay? Outside of a healthy lifestyle, which you don't have to market that. But if they are selling something, that's automatic credibility question mark.

A (14:39)

Right? And especially just drill down just very briefly on peptides. That's the latest one. The Last test was 14. People like, there isn't tests on this stuff. And also the danger of using mixed compounded things that you just. The sepsis issues are alone are problematic. But talk a little bit about this.

B (14:56)

You've touched on a couple of these things. So first of all, right now, most of these are from China. There are some compounding labs in the US that are also questionable. But if you actually analyze what people are getting as one of these peptides, 20% of them have all sorts of impurities or are not even the peptide that they're purported to be. As you mentioned, they might not be sterile. And you're getting these into your bloodstream. So people think, I'm just putting it under the skin. No, it's getting into your bloodstream through the capillary network. So it's a very dangerous thing to self inject when there's no proof of safety or of any efficacy that it's helping. So it's a misplaced trust and it's also a tremendous amount of confirmation bias, Kara, because these are very expensive. So when you take these injections and some of them are taking stacks of peptides, why would it not work? You've paid so much money, you must feel better from that, right? So it's just so sad to see these promoted. And now we even have the idea that the FDA is gonna take away the ban. The ban was appropriate on these unregulated peptides. We're not talking about GLP1 peptides, we're talking about all the others, right?

A (16:09)

No, no, no. I think that the complaint they make is that, oh, it's the FDA trying to keep this from us secretly, which is also part of a plot. Now, when you talk about this, what do you think the biggest problem with these sort of circuses are? Is it that they can reach people more quickly? Is it the new social media environment? I mean, this has gone on since Ponce de Leon. Like, let's be clear, Kellogg's was started as sort of a scheme of cereal. So it's not a new and it's not an American phenomena either, by the way.

B (16:35)

Yeah, well that's because concurrent to all this, you know, noise and grifters and whatnot, there has been a big push in the biotech world to try to reverse aging. And there are very intriguing science approaches like for example, the so called cellular reprogramming or the senolytics stem cells. And so there are some real science initiatives that are exciting. Yeah, they look good in rodents and mice and rats. We have no data in people and there's some dangers about going forward in people. But the point is. So that has helped to take this into center stage. So you have some real science, then you have the pseudoscience marketing stuff and then you have this other area that I'm most enthusiastic about, which let's just not try to reverse aging so much because it may not ever work. There's a lot we can do right

A (17:29)

now just to have a better life that is longer. So talk about the upper limits of health span and what age which biology wins in the human body starts to break down no matter how good medicine gets. I mean, Scott Galloway, we always joke, biology is undefeated so far on this planet. So you studied in 2008 the welderly or people who are at least 80 who have never been sick or had a chronic illness. As you noted, more than 90% of Americans over 65 have at least one chronic disease. So talk a little about the upper limit of this which you're trying to do here.

B (18:03)

Yeah, I mean, I think the upper limit is we can certainly get most people. We should be pushing towards everyone being a super ager as defined by 85 without cancer, without cardiovascular disease and without any neurodegenerative disease. That's what we should aspire to achieve. We may not get way beyond that. On average, there will be people like Lee Russo, the patient of mine in the book who just is about to celebrate her 100th birthday totally intact. But even if we get to Most people at 85 with intact health span, you can see that through now. You can see that that's a possible.

A (18:45)

The cost savings are enormous too.

B (18:46)

Oh gosh, you don't have. With Alzheimer's and the treatment for cancer, just as you say, Kara, the economic burden is just ginormous and so no less the health burden. So that's what we should be pushing on. You can see that this is achievable in the years ahead. It all starts with the prevention. So today everything is treat, treat, treat. We have to go into prevent, prevent, prevent. And we never really had the way to do that before. That's what's really new here.

A (19:19)

Talk about the key findings when we think about aging genetics. I know there was a study published earlier this year in the journal Science suggests that longevity appears to be about 50% heritable. If genes can reveal more about aging, how does that shift the focus on longevity research and ultimately impact what research is funded? If the FDI's dicking around on peptides, which they are, what is most important to be focused in on when you're thinking about this welderly population?

B (19:49)

Yeah. So the genetics of healthspan is very different than the genetics of lifespan because again, if you have those 15 years, that gap, and you're incapacitated one way or another, that's your genetics. Maybe it has 50%. But the health span as we've studied in others, has a lesser genomic role because a lot of that depends on your lifestyle. And so that is really one of the essential things which we don't do enough. And hopefully when we have individualized forecasting, we'll do much better. Because before we could say, well, you're at risk for something, but we could never say when. So you know, risk for Alzheimer's when you're 66 or when you're 99. That's a big difference. Now we can say when that's a huge difference. And when we tell a person when who's receptive, they may actually start really getting on a lifestyle kick. Of course, which is not just diet, exercise and sleep. There's many other factors, as you all know. So that's the beginning of a prevention story, is when you can forecast accurately.

A (20:55)

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B (25:29)

Yeah, so this is a big part because bad food intake or beverages can promote inflammation and also knock down our immune system. So we have to pay a lot more attention to that. And America is the highest consumption of ultra processed food and acknowledging that not all ultra processed foods are bad, but within that group there are some that are really noxious, that really rev up inflammation in our body. So we want to minimize those and there's things that we could do to change that. American diet to make it healthy and it doesn't align with what changes have been made recently.

A (26:08)

So it is up to the individuals to avoid ultra processed food or should there be legislation and regulation to curb the abundance of ultra processed food in our diets?

B (26:16)

Yeah. So Big food is of course in command here and it seems to be beholden to the Department of Agriculture and our government has really not done enough to take it on. Of course has tremendous lobbying power. But what we want to get out there is that we know the diets that are anti inflammatory, that are Mediterranean plant based of low red meat content, you know, trying to eradicate the harmful group within ultra processed food. So getting that out without the distortion that we're seeing, you know, currently is important. So you know, animal protein overall is not our best source of protein. And also don't want to overdose on protein because if you take too much of that in particularly animal derived, you're going to promote inflammation too. So the balance of food is really important and we're way off as a country.

A (27:11)

Yeah. The reason I went to Korea is cause I went to a school where they were feeding the kids astonishing lunch. There was rice of course, but there was also fermented foods, miso, healthy proteins, tofu, miso. You couldn't believe what these kids were eating and they learned from an early life. Now they do eat junk food too, but it's a really interesting basis and every school had a nutritionist. It was really quite something to watch.

B (27:37)

Why aren't we doing this? That's exactly what should be done.

A (27:40)

Yes, exactly. But moving on from food, in the book you reference a quote, Outspoken 47 year old sentimillionaire taking over 110 supplement pills a day. I think I know who you're talking about. New research suggests the roughly $209 billion global market for dietary supplements is projected to double by 2033. Talk about why so many people are convinced that vitamins and supplements are effective ways to increase their health span. Now let me just say some are good for you, but often like for example, someone was eating a fish oil supplement and they're like Kara, what do you think of this? I'm like it's fine, but eat a piece of fish would be a better choice. Like I guess if you're not eating fish and it's not a bad supplement necessarily. But you know, and there's a couple that are probably a good idea, talk a little bit about that because they get mixed in with the ones that aren't.

B (28:30)

Yeah. So this supplement part is really where the gaps are the vitamins. I mean, if you include something like a multivitamin, which has at least some randomized trial data a bit, it doesn't have a big effect in older people, but it has at least a small benefit. But when you get into the supplement side, unless you have a deficiency, if you're a healthy person and you have a good diet, as you alluded to, you're better off to get those things from your diet, from your normal intake than, you know, you'd have to take a lot of Omega 3 fish oil supplements to get what you could get in your diet. If you just concentrate on the right diet, that takes out the supplement story, you know, and you save a lot of money.

A (29:15)

Are there any supplements you think are worthwhile besides multivitamin, which I think maybe, maybe not, is what I've come to the conclusion.

B (29:22)

Well, the one that's gotten so much play in recent times is creatine. And creatine, the only data that really exists at solid is that if you work out, you do a lot of strength resistance training, it'll reduce muscle soreness afterwards. But beyond that, does it help the brain function or other things? We don't know. The data are inconclusive. So that one has lots of attention. People are all on this creatine kicks. High dose creatine, there's just nothing to support it, right?

A (29:51)

No. I do a creatine after I work out. That's the exact time. That's the only thing I use it for. And people are like, oh, you're taking it? And I said, only for that. What's interesting about the supplements is they think it's gonna solve 20 other problems, right? I'm like, it's good for that. Or, you know, the hyperbaric chamber stuff. I go into one and I was like, what did you think? I was like, are you fucking kidding me? Unless you have the bends or a wound, I wouldn't recommend it, you know, Oh, I get tired. I was like, you don't need more oxygen, just breathe. It was really interesting. And I did it on purpose to say, this is fucking ridiculous. Even if it's, you know, the same thing. A lot of them, all of them, I did a cold plunge. I'm like, it's fun, I guess. Or a sound. I did a sound thing.

B (30:34)

That's a stress test for heart disease.

A (30:35)

That's correct.

B (30:37)

Your blood vessels totally constrict. And if you have atherosclerosis in your arteries, your heart.

A (30:43)

Yes.

B (30:44)

Yeah. So to advocate things like that with no data particularly where there's danger. It's great that you're on this because you'll have the anti influencer impact.

A (30:55)

Yes, that's what I am. I'm the opposite, I'm obs. But some of them, like if you have workout a lot creatine. Sure, sure, why not?

B (31:02)

Yeah, I don't have a problem with vitamin.

A (31:04)

You're not getting enough fish. Sure, right. That sounds good but the thing that

B (31:08)

gets me Kara is just making up doses of it. So you know they'll say oh, take three times the normal creatine and then it'll do all these other. No, because there's. Show me the data.

A (31:19)

Yeah, more means better. So you include environmental toxins, which I think are is important in the lifestyle, plus which include factors like air pollution and microplastics. Right. It was one thing to document the pervasive presence of microplastics in our air and water, but another to find it in our arteries, brains, blood clots, liver, gut, lung, placentas, testicles and other tissues. So talk about the solution for regular people who don't have a lot of time and money because it often can feel like we're surrounded by ultra processed foods, plastics and toxins.

B (31:45)

Yeah, well the micro nanoplastics worries me because as a cardiologist to see the remarkable study of of these microplastics in the artery inducing vicious inflammation locally and then a four to five fold higher rate of heart attacks and strokes. In the follow up of a couple years this was studied to me there are others but that really took the plastics worry to the highest level and we're not doing enough to try to reduce that in our air and our water supply and whatnot. So what you're bringing up is central in that our inequalities, that is the people who have the worst exposure, air pollution, microplastics, forever chemicals, the ultra processed foods, they need help. Of all the folks, they're the ones that have the highest burden of this. So we have to really work on that. And that's not been part of the longevity mainstream. It's all about catering to the affluenza, which are the people who don't need this the most. It's the people who are in the lowest socio and economic category that are the ones who are most to benefit.

A (33:00)

Yeah, One of the things I spent a lot of time talking about inequality actually, which is, you know, I think I interviewed a doctor who's working on obviously CRISPR and sickle cell anemia and she said, you know, If Elon Musk got sickle cell anemia, you'd be sure this would be a very inexpensive process, right? And about $2 million. It's very expensive and eventually it won't be. But, but one of the things I kept stressing them is that really like, everyone was like, what's the answer? I'm like, don't be poor. And they're like, that's not a good answer. I'm like, I'm sorry I can't sell you a supplement. But really the biggest dip in longevity has been among those who are getting killed by obesity with processed foods in polluted areas with enormous amount of stress. Homelessness is a health issue, no question about that. If you think of it that way, then it's economic to me. So every episode we get an expert to send us a question. Let's hear yours. Hi, I'm Amy La Rocca, the author of how to Be well, My question for Dr. Eric Topol has to do with the information that last week the American Heart association issued new dietary guidelines that directly contradict the dietary guidelines that were issued by Robert Kennedy. And given that so many doctors have their own proprietary lines of supplements and protein powders and other nutritional products, where in the world are Americans meant to look for safe, reliable health and nutritional advice to increase and improve their health spans?

B (34:37)

Yeah, well, that's a great one because firstly, the American heart, as you might imagine, got it right. They actually had evidence based guidelines about diet as opposed to what was done through RFK Jr and HHS. So if you want to follow where

A (34:53)

there's the facts, explain the difference between them, between what RFK said, what RFK

B (34:59)

has, you know, been advocating. Well, fat, the wrong oils, you know, raw milk. I mean, stuff that's just, you know, looney tunes. Now some of it is right, that is, we want to foster the high consumption of fruits and vegetables and plant based. But to have meat, red meat, which is advocated by hhs, is wrong. It's okay to have red meat, but it should be infrequent rather than something that you should have at the top of a food pyramid. Right. So some things are just completely unfounded in the current, hopefully short term US hhs. Whereas the American Heart went through all the data and that guidelines piece is well done and it sets the record straight. The problem, of course, in general, I mean, you brought up some of the people like Brian Johnson and then there's Gary Breca and all these people, and a lot of these are very close to RFK and having an effect Even on him, is that they have ideas that are not substantiated by any evidence. And this is of course, really unfortunate, but you can tell that the basis for their ideas are things that they're selling, typically. And so that's where you really eliminate the lack of evidence. Combined with, oh, you can buy this supplement or this peptide or whatever, then you already know that stay away. Because it's just not gonna help you to follow a person or, you know, a group that's working in a fact free world. And we have a lot of really good evidence for these things.

A (36:42)

Yeah, The American Heart association basically said to eat a Mediterranean. Mediterranean diet, Heavy on legumes, fruits and vegetables, whole foods, and light on animal proteins. Not getting it out of your system, it's just lighter on it. Get your protein through fish or, you know, spinach and your fiber through whole foods. Like an avocado, for example. People don't realize how full of fiber an avocado is, for example.

B (37:03)

Oh, yeah, yeah. Fiber maxing. That's good. Fruits, vegetables, legumes, great. And yeah, protein great from fish, obviously. Many other great sources. Yogurt, tofu. So there's so many great foods out there that provide the kind of ideal intake that is anti inflammatory. And we have randomized trials for the Mediterranean or Mediterranean like diet. We have huge cohorts followed for 20 plus years that show the people that have the greatest health span are people that are following a very healthy diet. So pretty much this is incontrovertible. But what's happened is that we have some actors who are trying to subvert what the evidence shows.

A (37:55)

Right, right. In order to sell things. I mean, I did a long interview with Brian and I said, you are a study of one which mean it's meaningless. He's like, I'm just sharing it. I mean, it doesn't matter. I was like, it doesn't matter what your experience is. It was somewhat sad though, because of his obsessive measurements.

B (38:12)

It's sad. But you know what's really bad about this, Kara? So, for example, he and Atiya and so many others were. They were on the rapamycin leaderboard. How much rapamycin they take? They all had different doses. You know, it's kind of like when the error is in a newspaper, you never see the error. Well, these people stopped taking their rapamycin because they were getting a lot of infections. No surprise because it's a very potent blocker of our immune system. And so here you go. This is. Oh, this is gonna extend your health span. Your lifespan, no data in people. And you have these influencers who got everybody onto this rapamycin kick. All the bro folks, you know, then this is a typical thing where then they stop taking it. Cause they have all these side effects. But all these people are already hooked.

A (39:01)

Yeah, yeah. The problem is the answers are very basic and simple and inexpensive. And so it's not a quick fix. And I think there is an ele of quick fixiness that people desperately need. And it's the same thing with diet. Right. It's pretty basic in terms of how you change your lifestyle.

B (39:18)

Yeah. I mean there's another dimension to this that I'm sure you're on it which is getting unnecessary tests. This is also heavily promoted. Whether it's a total body MRI or hundreds and hundreds of blood tests and on and on. And this is another part of that. No evidence. But I do it and you come to my clinic and I'll do all these things. And so I went to one. Oh gosh.

A (39:43)

I was like what do you need this to know for? Why is this information helpful to me now? It sometimes works. My brother doctor went to speaking of cardiology, hadn't had a calcium test. Turned out he had one when he went into Medicare and he had huge blockage, the widowmaker blockage essentially. And it was great. That was a great test to get. And he removed it, then he was fine. Then he just had the surgery which was really quite less invasive than it's ever been. Really astonishing with the situation.

B (40:15)

Right, right.

A (40:16)

So I think people are hoping for those ideas that you find something drastic.

B (40:20)

Yeah. The problem is when you get at to the real data, particularly for the total body mri and there are ways to assess a coronary artery non invasively better than just getting a calcium score. But you wind up. They did balances. Yeah. The balance about this is that more people are hurt. Right now we don't have any evidence that there's a net positive. And on all these rabbit holes of chasing down incidental findings that are spurious. So this is a real problem because that goes hand in hand with the supplements and the peptides. It's all part of that mix.

A (40:56)

Explain how people are hurt by these tests. Besides having way too much fucking information like that you don't need.

B (41:03)

I've had patients with total body MRI who found a pulmonary lung nodule. Then they had a biopsy eventually and then they had a collapsed lung and they had to be in the hospital with a chest tube. I've had patients who had a liver nodule which Actually turned out to be a benign cyst, but in the process of a biopsy, almost bled to death. So when this leads to getting tissue to find out what it is that you never really wanted to know in the first place, you can have pretty severe, potentially even life threatening consequences no less. Big expense and big anxiety.

A (41:41)

Yeah, it's like a bad facelift, which I've seen many on some of these guys. We'll be back in a minute. Foreign.

B (42:02)

Fest is heating up at Lowe's. And for a limited time, we have the extra big deals you need to impress guests. Get your outdoor space ready and save $50 on the select Cobalt 24 volt blower kit now $79. Plus save 80 on a char broil performance four burner grill now $199. It's springtime and our best lineup is here at Lowe's, valid through 413 while supplies last selection varies by location. For the last 10 years, everything in American politics has basically revolved around one man. And as a political journalist who came of age during Donald Trump's rise in 2016, I've had a front row seat. I am officially running for President of the United States. It's going to be only America First. America First.

A (42:55)

Thousands of supporters of President Trump stormed the U.S. capitol building.

B (43:00)

But is it possible to talk about politics without talking about Donald Trump? That's the question I'm going to ask in our new show from vox.

A (43:09)

The idea of like a post Trump or not exactly Trump focused show can exist because he's not really driving any agenda items. It really does feel like so reactive.

B (43:16)

You know, I think this Iran thing is also going to cause a big split in the gop. So far it doesn't among like people who say they're MAGA voters are still with Trump. But like for the first time, you see on a major issue, open opposition from the start of this war. I'm Estet Herndon and welcome to America. Actually. Hi, I'm Brene Brown. And I'm Adam Grant.

A (43:38)

And we're here to invite you to the Curiosity Shop, a podcast that's a

B (43:42)

place for listening, wondering, thinking, feeling and questioning.

A (43:46)

It's going to be fun. We rarely agree, but we almost never

B (43:50)

disagree and we're always learning.

A (43:52)

That's true. You can subscribe to the Curiosity shop on YouTube or follow in your favorite podcast app to automatically receive new episodes every Thursday. Let's talk about real biotech interventions because as you said, astonishing high tech breakthroughs in the biomedical area and they're transforming our approaches to diagnostics. For example, you've talked about how AI could propel the biggest transformation in the history of medicine. Talk about how important AI will be in drug discovery.

B (44:21)

Yeah, I mean, I Wish we'd had AI when GLP1 drugs were getting their legs. But the problem is we didn't. And it took 25 years when it started out as a diabetes drug to become an obesity drug. Had we had AI back then, we would have said, oh, hey, test this for obesity. But now we do have AI and we're seeing drugs that are truly discovered by AI. And you know, we have some that are pretty advanced clinical trials now, for example, to get rid of scarring of tissue, which we never thought would be possible. I mean, in medicine we thought if it's scarring, it's done, you know, and we're seeing drugs starting to crop up in late trials. That is, they've already passed, they're safe and they may wind up having lots of efficacy in areas that were not envisioned previously. So that's led to some people like Demis Hassabis to say, you know, we're going to cure all the diseases. I have a different look on this. My thought is we are going to have a big jump and speed breath in drug discovery. But I call them prevmeds. They're not going to be treatment medications, they're going to be preventive medications.

A (45:35)

Right. Which you don't even know you got it in the first place.

B (45:38)

So, you know, the GLP1 story is an exemplar, but what if you had drugs that could really knock down brain inflammation? So you never got Parkinson's or Alzheimer's. And, and we have many candidates in the pipeline now that we didn't have before. So there's a gold rush with AI for drug discovery and it isn't just even to discover new molecules, it's to be able to go high velocity and get right quickly.

A (46:05)

I interviewed Reed Jobs about it because he's a terrific guy and one of the things he's working on is hepatitis to prevent liver issues which leads to cancer. But you never get the hepatitis in the first place, you never get the cancer in the second place, which seems very promising to me. But explain, say one of the things you talk about. The GLP1s should have been studied much earlier and they have potential, life changing potential beyond weight loss, which is a good thing too in some ways. Talk about a counterargument to any of this, because Once patients with GLP1 stop taking Wegovia or Ozempic and now there's pills coming out which will be more on a maintenance schedule without the shot required or the refrigeration. It is a lifetime commitment, very similar to a statin. For example. Talk about the idea of how you keep people on these kind of things that can be life changing and helpful for other diseases so they understand it better.

B (46:59)

Yeah, so I don't like forever drugs. And as you mentioned, statins, blood pressure medicines are examples of that. And so we don't need to add another forever drug if we can avoid that. Right now we don't have a good mechanism to wean people completely. But I actually think that will be possible in the future that we don't have to have them on, you know, high doses of GLP1. So we have these now two pills that are like the injectables but not quite as potent.

A (47:30)

Right. They're from Eli Lilly and Novo Nordisk.

B (47:33)

Right. And they're both peptides that are packed into a pill with very hard to get eek out much out of that. But there are pills, low cost, small molecules can be manufactured at scale where the actual cost is pennies. So we're going to get the cost way down and that will make it global for all people, not just for those who can afford it. And then the next thing is, can we get to a strategy, whether it's a lower dose small molecule pill or some other way that we can get people so that maybe they're taking it but you know, much lower quantities or not at all. We know for example, the muscle mass that you lose when you lose weight. There are a lot of these companies are invested in these muscle building adjuncts. But actually, you know, if you do strength training while you're taking these drugs.

A (48:26)

Right. Combination. I end up interviewing a woman who lost several hundred pounds, started off as an obesity drug, but then they gave her a whole program of nutrition teaching how to cook correctly, combine it with exercise and so it creates the three things together are what's critical, I think.

B (48:42)

Absolutely. So I think we're gonna learn about this in the future because the idea that it expanded now to many other indications that people would take it. We have to figure out a longer term strategy. The companies, the duopoly if you will, they don't really have a great motivation to wean people from the drug, but we do. I mean if we can get away with keeping the weight off or having the sustained benefit of the inflammation in the, that'd be great. I should add though, there are many other candidates in the pipeline that have similar effects on the immune system and inflammation that we might turn to those as a longer term maintenance strategy. They're just not as far along in the whole process.

A (49:28)

Right, right. You wrote an article in your Ground Truth substack explaining why all mammograms should incorporate AI. Talk about the use of AI in mammograms and how it could lead to improved accuracy and how long will it take until AI is incorporated into not just mammogram, all diagnostics. Now, I know there's been some, like one of the tech people, like, well, no more radiologists. I'm like, no again, they're always so all or nothing on everything. And I'm like, it's an aid, it's a tool. So talk about incorporating mammograms, for example.

B (49:58)

Yeah. So this is frustrating because we now have three ways, three different AIs that should be part of every mammogram. So every woman should have, for example, the better detection. Because we know from the national cancer institute that 20% of breast cancers are missed by mammograms today. And AI picks those up and then some. So it increases the yield by about almost 30%. Then the next one is that we have a. If it's normal mammogram in a woman, well, what about the risk in the next three to five years? And we have an FDA cleared AI to do that. Then we also have one that picks up heart disease risk from the breast artery calcification very accurately to say that, oh, this woman has a very high risk for heart disease, which would often be not even in the awareness of that woman. So we have three AI tools and almost no women in the United States are having the advantage of these. And the only one that they are getting exposed to in this RadNet network, they have to pay out of pocket $40 to get the AI initial interpretation, which isn't the other two AIs. So it's frustrating because we've iced this. The data are clear, the FDA approvals are out there, but we're not incorporating into medical practice. And this is where a lot of people. There's a backlash to AI out there in the public, but they don't realize that there are a lot of good things that AI can bring to us, but we're not bringing that in.

A (51:31)

You know, Exactly. No, exactly the thing. But that's because they promise them as an all solver, you know, the same thing with supplements. Like some supplements are fine. Anyway, let's end by talking about some of the structural and institutional barriers preventing the universal expansion of healthspan. Many of the ways we alter the pace of aging carry a serious risk of cancer. Explain the connection to cancer and how you weigh the positives and negatives when you think about that.

B (51:57)

Well, I mean, I think we know that the risk of cancer, there's a lot of preventable aspects to it, and we reviewed lifestyle factors. We also know that the immune system is a big driver when it starts to lose its protection as we get older. That's when the ability for cancer to develop and spread in our body makes us so much more vulnerable. So. So we have to counter that. And the way we're going to do that in the future, which we never had before, what's amazing about this, Kara, is here it is 2026, and we have no test to say your immune system is healthy or it's down, you're vulnerable. And that's something that we're on the window of having, not only through an immune clock, a piece of aging of your immune system, which will someday be routinely available, but now we also have this thymus. That is the gland that everybody thought was involuted and became fatty and worthless after our teenage years. Well, it turns out when you do AI of the thymus, you find out that even people in their 70s and older, some of them have intact thymus. And guess what? They also have intact health span. So the point here is that we're right on the brink of being able to say, particularly when people are 50 and older, your immune system's starting to show signs of vulnerability. So we're going to give you a vaccine to amp it up, or we're going to do this or that to amp it up. Because we have so many ways to rev up the immune system that we've learned for cancer treatments so many ways. And that's something that's in a high velocity of new dimensions, of how we can rev up an immune system in people who have cancer to treat cancer them. But now we have these two ways, and probably more subsequently, if we start to get on top of the immune system before a person has cancer and get them. Like, for example, the shingles vaccine has had incredible impact to reduce alzheimer's. Unexpected.

A (54:03)

I had mine. There's two of them, folks.

B (54:05)

Yeah, because it revs up your immune system, not because it works against the virus. Well, the same thing for cancer. And these could be generic vaccines that are not against a virus, but rather vaccine that's just trying to get your immune system amped up. So that's where I think we're gonna see some big advances. And it's just because the system that lets cancer take hold in our body and allow it spread, we didn't have a way to measure it. And that's one of the aspects of the excitement in the science of aging is understanding and respecting. And also this whole idea that maybe we could keep the thymus healthy in

A (54:43)

everyone throughout our lives, which would provide enormous benefit. Absolutely. And you stuck on vaccines, which we didn't get into. But I interviewed the guy who won the Nobel for the MRNA vaccines stuff and the whole. I talked to everyone in that lab at University of Pennsylvania.

B (55:01)

Yeah, Drew Weissman. Yeah.

A (55:03)

Yes, exactly. He was amazing. He's like, he's sort of like a very even handed guy who's like, well, it's really important. We could have a vaccine for cancer, for hiv. There's all these amazing things. And then all of a sudden he goes, but RFK is a murderer. Essentially. I was like, oh. In his most normal tone. But everyone in that lab was thinking of moving elsewhere because our country was way ahead, has been way ahead. But moving to France, moving to Canada, moving to places that they are not getting these ridiculous research cuts because they are on the cusp of doing that, which is really kind of like shooting yourself in the foot.

B (55:37)

Yeah. No, the idea it a dream that we could have vaccines that would help us prevent cancer. We're gonna get there now that we have a way to find out who

A (55:46)

we think France is gonna get there.

B (55:49)

Collective right? No.

A (55:50)

Well, he was saying we're gonna rely on China for this. That's what's gonna end up happening. Which is problematic on every issue, right?

B (55:56)

Absolutely.

A (55:58)

So health inequality, as you said, is a huge problem in the US and globally. You note the lack of universal healthcare in the US is holding us back. Korea has universal healthcare. They're so healthy in that regard. A lot of preventative stuff. Research shows that rich people not only live longer, they get more healthy years after age 50 than poor people. This should not come as a surprise to anyone, but the lack of universal healthcare in this country, to me it's another thing I point to. I'm like, you know how you want to exclude longevity? Universal healthcare basics. And then rich people can pay for more of the bells and fucking whistles if they feel like it. But what would a fair health care system look like in America?

B (56:32)

Well, it would be where insurance companies are not ruling the roost and only concerned about the one year outcomes of big employers or the actual direct consumers that cover so we not only have lack of universal healthcare, but we have such a perverse incentive that we don't have a country where we're trying to promote and prevent diseases, promote healthspan, whereas other countries like the UK and just about every other high income country around the world, their incentive is, is reduce the health burden of chronic diseases, age related especially and reduce the economic burden. So they go hand in hand. Whereas here we have a mal incentive to do that that even transcends the lack of a universal health system because we have no way that preventing these diseases, besides the fact that people could benefit. The financials don't click and so we're at a disadvantage and we could see the prevention story unfold at other high income countries because they get it. The investment for prevention and detection and forecasting is so easy to see the benefits. Whereas here, for people who don't know,

A (57:49)

our country pays Double health care, $13,000 a person versus six in most developed countries.

B (57:54)

Oh, right, right, exactly.

A (57:55)

It's crazy amounts of.

B (57:56)

No.

A (57:56)

What?

B (57:56)

We get to be sicker and we're sick totally. And we're gonna keep that up unless we start to get a new mindset of preventing diseases which starts with prediction and finding high risk people. But if we don't break through these barriers that are holding us back with our system of the financial coverage that is not the last thing is for prolonging healthspan, which is a multi year story, then we're not gonna make the advances that others will certainly be able to achieve.

A (58:29)

What is, what do you im has to happen? How do you get there? Because there's been multiple attempts to do it. You know, Hillary Clinton was you know, digging the ditch on that one many years ago.

B (58:37)

But yeah, I mean I think unfortunately the lobbying power of these forces that are holding us back is so strong that we haven't been able to override that. It probably is only going to become achievable when we see whether it's some systems within the U.S. let's say a Kaiser or Veterans Health or more likely other countries, markedly reduce their healthcare costs from prevention. That will maybe be the stimulus ultimately in the years ahead that we better get on this. But right now there's no attention being paid to this potential here. But you know, having been an advisor to the NHS and other countries, I know it's happening elsewhere because they have the great interest in keeping their whole population as healthy as long as possible.

A (59:28)

So I want to ask you a last question. You emphasize both the power of evidence based medicine and the Risks of hype and pseudoscience. And at the same time we're seeing a growing skepticism toward modern medicine in the US and distrust of experts and institutions. Now that may be waning down. And it's one of these things we go through. But how do you think we can distinguish between genuinely transformative advances like AI driven medicine and GLP1 drugs and the kinds of, of unproven interventions that gain traction in the wellness space? Talk about the distrust of science and what that might do. How do we regain that?

B (60:01)

Yeah, well of course we had it before COVID We started to have this fabricated data that led to vaccine questions and autism, which was completely bogus. Then it was amplified through Covid and unfortunately the science community didn't stand up. It led this orchestrated finance backed minority to make serious holes and there were missteps of public health agencies and the government. So it just all added during the pandemic to take the questioning of the medical establishment at the highest level. You know, really a disregard, a dis that these people don't know what the hell they're talking about. What do you mean? Expert? I do my own research. So we got to this height and hopefully we're starting to.

A (60:46)

And the medical establishment has plenty of, to blame in terms of being high handed, not being open to, open to

B (60:53)

a number of things, listening to the concerns, that is having respect for the doubting folks out there and trying to provide the evidence that their concerns are not real or they should be balanced by, for example, benefits and risk. But anyway, so we're still not that long from the COVID 19 pandemic days where it's at height and a lot of these people have been now empowered at the highest levels of our government agencies. So that helps perpetuate it. So in the meantime, the medical establishment has still not gotten its voice, you know, the likelihood of somebody in science and medicine to be trying to ante out beyond social media and getting good information out there, it's a tiny minority, it's so crowded out out by the others. So we haven't put a dent in this. And in order for us to change this to turn the tide, we got to see a lot more people in the medical community who are credible, who are not selling something, who are going to stand up and get the facts out so that people know. And we also need compelling data. So we're not going to get AI into the mainstream until the data is incontrovertible, powerful, replicated independently. But when it is, we can't keep having poking holes and questioning it, because it's really going to become the standard of care. That's just one example. So, you know, we have unfortunately so many conflicts out there with people who are, you know, all these tests and supplements and peptides and whatnot, and they're getting the audience. They say, we have the secrets that the doctors won't tell you. And don't wait for this stuff to get approved by the medical establishment because it works. The rapamycin is kind of the prototype story of that. And I think hopefully people are gonna learn that that's not the answer. The answer is have the evidence. Restore the trust in the medical community. Get more of doctors and people in life science to be activists.

A (63:04)

Talk about it.

B (63:05)

Talk about it, write about it.

A (63:06)

Guess what? I have two billboards in Times Square and I'm gonna show off. That's what I'm doing.

B (63:11)

Oh, wow.

A (63:12)

I'm sick of this shit.

B (63:13)

Yeah, well, me too. I'm so glad you're on it. I mean, I can't wait to watch your series because I think what you've done is.

A (63:20)

I've talked to actual experts. Yeah.

B (63:22)

Wow.

A (63:22)

I'm sick of it. I'm sick of it. I was like, guess what? I'm going to play your game and I'm going to kick your ass just like I always did Before, I was right about the tech moguls. Now I'm going to be right about this.

B (63:33)

Show off the bro. Science is whether it's Joe Rogan, Elon Musk, Uberman, all these people. You know, this is a big part of this. You know, they're an underpinning of all 100%.

A (63:49)

I would agree with you. And I took ketamine just for you. Just. I would not recommend it. I would not recommend it. But I did it, and I did it in a medical setting, and I say, do not do it. It will not help you unless you have some. And that. But there's some problems, Promise even there. There's promising stuff. It's just the abuse of it, right?

B (64:07)

That's right. No. Ketamine can help some people, but have ketamine clinics all over the place we have in California. I mean, this is crazy stuff.

A (64:14)

Yeah, it's crazy stuff. Anyway, Dr. Topol, I really appreciate it. We're gonna be doing a lot more, and I'm gonna be doing a lot more because I think it's a huge opportunity to make people healthy, save money, have economic impact, and have everybody live longer Instead of just 14 men from Silicon Valley. So. So I really appreciate it.

B (64:32)

All. Thank you.

A (64:33)

Thank you.

B (64:34)

I really enjoyed the talk with you.

A (64:35)

I enjoyed it too. Thank you. Hi everyone. Want career advice from Kara Swisher? Now's your chance. Send a video to onoxmedia.com and you might be featured. I can't wait to see what you've got. Ask any questions? Question? I'll try to answer it. Today's show was produced by Christian Castro, Russell, Michelle Eloy, Kathryn Millsop, Megan Birney and Kalyn Lynch. Nishat Kirwa is Vox Media's executive producer of podcasts. Special thanks to Madeline LaPlante, Dubie and Eamonn Whalen. Our engineers are Fernando Arruda and Rick Kwan and our theme music is by Trackademics. If you're already following the show, you're on the page path through a health span expansion. If not, enjoy the Longevity Lifespan Circus. Actually, they're grifters. Go Wherever you listen to podcasts, search for on with Kara Swisher and hit follow. Thanks for listening to on with Kara Swisher from Podium Media, New York Magazine, the Vox Media Podcast Network, and us. We'll be back on Monday with more.