313 | Eric Topol on the Changing Face of Medicine and Aging

Medical science is advancing at an astonishing rate. Today we talk with leading expert Eric Topol about two aspects of this story. First, the use of artificial intelligence in medicine, especially in diagnostics. This is an area that is a perfect match between an important question and the capabilities of machine learning, to the point where AI can out-perform human doctors. And second, our understanding of aging and what to do about it. Eric even gives some actionable advice on how to live more healthily into our golden years. Blog post with transcript: https://www.preposterousuniverse.com/podcast/2025/05/05/episode-313-eric-topol-on-the-changing-face-of-medicine-and-aging/ Support Mindscape on Patreon https://www.patreon.com/seanmcarroll. Eric Topol received and M. D. from the University of Rochester. He is currently the Gary and Mary West Chair of Innovative Medicine in the Department of Translational Medicine at Scripps Research. He is also the Founder, Scripps Research Translational Institute, and Senior Consultant, Scripps Clinic, Division of Cardiovascular Diseases. Among his awards are the Hutchinson Medal from the University of Rochester and membership in the National Academy of Sciences. His books include Deep Medicine: How Artificial Intelligence Can Make Healthcare Human Again https://bookshop.org/p/books/deep-medicine-how-artificial-intelligence-can-make-healthcare-human-again-eric-topol/12786538, and Super Agers: An Evidence-Based Approach to Longevity https://bookshop.org/p/books/super-agers-an-evidence-based-approach-to-longevity-eric-topol/21872909. Web site https://drerictopol.com/ Scripps web page https://www.scripps.edu/faculty/topol/ Google Scholar publications https://scholar.google.com/citations?user=E2-uIQYAAAAJ&hl=en Wikipedia https://en.wikipedia.org/wiki/Eric_Topol Substack https://substack.com/@erictopol Bluesky https://bsky.app/profile/erictopol.bsky.social

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

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• 0:55Sean Carroll?

  Hello, everyone. Welcome to the Mindscape Podcast. I'm your host, Sean Carroll. A couple of years ago, 2023, I did a holiday message entitled "Reflections on Immortality." This was in response, or at least inspired by, a workshop we had at Santa Fe Institute on immortality, what would mean, how you might get there. And I mentioned there that a lot of the people at the workshop basically said they don't want immortality. Like, that's too much. Either personally, they couldn't imagine what to do for all that time, or socially, they think that society would stagnate if people just live forever rather than being replaced. That's fine. You can argue whether or not you'd want to live forever or not.

• 1:36Sean Carroll?

  Most people, though, would want to live a little longer, at least, than they probably will live. We're very interested in longevity and aging, and not only living, but living in healthier ways. I just now, for this intro, looked up the graph of life expectancy in the United States for the last 100, 150 years or so. And it's been going up. That's the good news. It went down once. In this particular graph, shows five-year bins, right? So, only once in the 20th century did the life expectancy decrease from one five-year bin to another between 1915 and 1920. I'm not exactly sure why that was. The flu? The Spanish flu, maybe?

• 2:22Sean Carroll?

  Until 2015 to 2020, it also decreased. It also only decreased a little amount, okay? In 1920, it was 53 years old, the life expectancy from birth in the US. In 2020, it was 78.8. So it's gone up quite a bit. That's impressive. But in 2015, it was 78.9. It was a little bit bigger. And we can talk about why that's true. The healthcare system, nutrition, whatever. That is the kind of thing we're going to talk about on today's podcast. Eric Topol is a leading medical researcher. Cardiovascular system is his specialty, but he's a broad thinker who's done a lot of work and has been thinking for a while now about medicine in a very broad way and been writing books about it.

• 3:07Sean Carroll?

  We will actually take a little bit, more than a little bit, of a detour to talk about his previous book, which was called Deep Medicine: How Artificial Intelligence Can Make Healthcare Human Again. He has this fascinating point of view that not only can AI be super duper useful in recognizing, diagnosing some medical conditions that human beings are not very good at, but in fact, it can be better than human beings in some very, very important ways. And, you know, we think about how to make an ideal system where there be both humans and AI there. But one of the steps there is making the humans understand that the AI can actually be pretty good at some things. It's not about AGI or superintelligence.

• 3:51Sean Carroll?

  It's about pattern recognition, which is what AIs are very good at. But mostly, in today's podcast, we're going to talk about Eric's new book called Super Agers: An Evidence-Based Approach to Longevity. And here, we're not talking about modifying the human genome to live for centuries or anything like that. We're just talking about living a healthier life and preventing disease in ways that are very plausible, very down to earth, very tangible, and can actually add several years, maybe decade, to an ordinary, human, healthy life expectancy. This is something which most people would sign up for if they had that option. And it's a combination of

• 4:32Sean Carroll?

  Understanding the diseases that tend to end our lives at some point. In particular, the fascinating thing that we learn is that many different sounding diseases are all related to the immune system and inflammation, which might be promising for sort of treating or preventing them. And then, of course, the other thing is that things that we individually can do, things that have to do with diet and exercise, as you might expect, but also mental health, mental acuity, social activity. These are all turn out to be really, really important for not only living a long time, but living a long time in a healthy way. So maybe this is a podcast, which unlike many Mindscape episodes, has a really tangible effect on how people live their lives.

• 5:17Sean Carroll?

  I hope it does, so let's go.

• 5:36Sean Carroll?

  Eric Topol, welcome to the Mindscape Podcast.

• 5:38Speaker 03

  Great to be with you, Sean. Thank you.

• 5:40Sean Carroll?

  So we're going to talk about a lot of things with medicine, aging, AI, things like that. But one thing, there's a little news item that struck me and I thought, I don't want to forget asking you about it while I have you here, which is, as a person of a certain age, I recently got the shingles vaccine. And now I'm told that this might even have a positive effect on preventing dementia in the future. That doesn't seem what it's there for. Is this something that is completely weird and surprising or true and understandable?

• 6:11Speaker 03

  Well, it's a mixture of your questions about surprising and understandable. It's really fascinating because there are these two so-called natural experiments whereby, you know, huge numbers of people got the vaccine just because of a policy change or a date change. So it's like a randomized trial. In fact, it's even better because there's no selection criteria. And whether it was comparing the new Shingrix vaccine versus the old live attenuated virus vaccine called Zostavax, or the vaccine, the old vaccine versus no vaccine, everything pointed to this about 20% reduction of dementia.

• 6:55Speaker 03

  And this is fascinating because while other studies had suggested this, they weren't like this ideal natural experiment.

• 7:04Sean Carroll?

  Yeah.

• 7:05Speaker 03

  So it does look like there's a twofer. It helped me decide to get the shingles vaccine because I don't do well with these vaccines in terms of acute reactions.

• 7:14Sean Carroll?

  It's unpleasant, yeah.

• 7:15Speaker 03

  But and I was lucky because of all things, this vaccine didn't knock me out like like some others do. But yeah, I think for people over 50 in the US, it's wise to get this because there really is an appears to be an added bonus. It doesn't mean for sure that the virus herpes zoster causes Alzheimer's, but it could be that just revving up your immune system with this vaccine helps. So it isn't unequivocal proof that there's a root cause of a virus for Alzheimer's or dementia, but it does certainly suggest the immune system plays a role.

• 7:55Sean Carroll?

  So we're still pretty unsure what the root causes are for dementia, for Alzheimer's.

• 8:00Speaker 03

  Yes, I mean, the theory of a virus like for multiple sclerosis, Epstein Barr virus, which is unequivocal, is very soft here. We don't have anything like the multiple sclerosis story, but there's still people who believe the virus plays an important role and perhaps in a subset of people and even other viruses besides the herpes zoster, varicillitis virus, may be invoked. So there's still work to be done on that one.

• 8:28Sean Carroll?

  Yeah, okay. I mean, there usually is, especially in medicine, it's very hard. Okay, thank you for indulging me with that. Now we can get on to the, you know, the work you've done, the books, et cetera. You know, part two of the podcast is going to be about your most recent book on aging, which is something everyone cares about. But previously, you talked a lot about the potential impact that AI can have on medicine. And I think this is perfect for this podcast because I love the idea of AI. I'm very skeptical about some overblown claims about artificial general intelligence, but here is an actual use case where you don't need to worry that the AI is conscious or intelligent or anything, you can just use it.

• 9:11Sean Carroll?

  So why don't you give us the like the big picture overview of why AI might be helpful in medicine?

• 9:18Speaker 03

  Yeah, I mean, in some ways, it's stunning, Sean. I mean, we're going to get into some of the concerns, of course, but some of the things that AI is bringing to us, we couldn't even have conceived, frankly. So perhaps the one that is just kind of knocks you out in terms of wow factor is the so-called machine or digital eyes, the vision that AI has, which is so, it makes our vision as physicians, experts in certain domains, look weak, okay? Because it turns out that the accuracy, once you train an AI to see things, if you will,

• 10:03Speaker 03

  is so much better, not just for the things that you're supposed to be looking at, but for finding things that you can't even see. So, for example, you know, the retina is a perfect example, because it turns out even ophthalmologists, the retina specialists, they can't see things that the AI can. So not just about retina disease, but about every system in our body, essentially. Not just the brain, but about risk for heart attacks and strokes and kidney disease and liver disease. And, I mean, the list goes on and on. So the point being is that there's this opportunistic aspect, because the supervision

• 10:44Speaker 03

  of AI is just extraordinary. And so that is something that I think we're just starting to get in touch with. No one had anticipated the richness of ability to interpret medical images, which is a big part of practice of medicine. But then we're also seeing some things that also are surprising. That is, one of the most important parts of medicine is making the diagnosis. You know, there were things that were listed as the three most important things, diagnosis, diagnosis, diagnosis. It turns out, we have 12 million serious diagnostic errors.

• 11:24Speaker 03

  A year in the United States, we see eight hundred thousand, eight hundred thousand Americans, either disabled or dead from these serious diagnostic errors. So it's hard to make things worse. Well, it turns out, you know, even though the medical community doesn't like to fess up to these problem of errors, these errors, the AI is making a big difference because it is so good at coming up with a differential diagnosis from a person's data, much better than we expected. So the chance of it being as good as one of the experts for coming up with the diagnosis like we see with the storied case presentations at the New England Journal of Medicine sort of

• 12:09Speaker 03

  thing. It's amazing. So this is another way accuracy, not just medical images, but also for helping making the diagnosis through what's really fascinating now, Sean, is this, we're not just seeing large language models, we're seeing large reasoning models. And so this is really helping that reasoning and following the chain of thought. So you can just say, how did you get there? How did you come up with these diagnoses? Right. And get the details of how the AI is thinking, if you will. Now, the other thing that I think we wouldn't have expected, and again, some of these are really outgrowths of the transformer architecture of AI. But now, when you go with a patient in a clinic

• 12:54Speaker 03

  visit, or even at the bedside, that interaction can not only be transcribed, that's, that's nothing, but what it can do is do all the downstream tasks. So it would do, like if you need prescriptions, follow-up appointments, procedures, labs, setting up follow-up appointments for, and nudges for things that were discussed during that interaction. Like, did you check their blood pressure? What are the values? And you get it back to the doctor. And, and even preauthorization to deal with the darn insurance companies. So what we're seeing is average for those who are adopting these, two to three hours less data clerk work for doctors.

• 13:40Speaker 03

  And then the other thing that's, I think, very refreshing is to see the patients getting empowered to make their own diagnoses through these tools. So whether that's for a heart rhythm or a skin lesion or ear infections in a child or urinary tract infection. So all around, they're seeing effects and they're just real starting to take hold.

• 14:03Sean Carroll?

  I love the example that you, you already mentioned it briefly, but I saw you give it in a talk and it was, it really stuck with me of this retinal scan. So you're literally looking at a picture of someone's retina and you ask human doctors, okay, is this a man or a woman? And they have no idea. It's 50 50. They're just, they're just guessing and the AI gets it right 99% of the time.

• 14:24Speaker 03

  Yeah, yeah, it's amazing. And we still don't really know why the AI is so good. But it just, that is perhaps the best single example of the gap between human eye

• 14:38Speaker 03

  discrimination and what an AI, when it's seen, trained with hundreds of thousands of images. It just, it's actually pretty mind boggling to me and, you know, I've known about it for years and there's just now so many other examples, whether it's a cardiogram or a path slide, an X-ray. I mean, who would have thought you could diagnose diabetes from a chest X-ray? I mean, these are crazy things, you know? So it's, it's wild.

• 15:06Sean Carroll?

  But it kind of makes sense, you know, because you're kind of using the AI for what it seems like it should be good at. It's pattern recognition, right? And it's, it's looking for differences and human beings are okay at that, but they're not perfect. But you're not trying to shoehorn the AI into something that being something that is not.

• 15:25Speaker 03

  That's right. I mean, and what's really interesting is that capability was just an outgrowth of deep learning without the extra.

• 15:34Speaker 03

  Turbo charge capability of the newer models. So yeah, I mean, just think of where we're going to go with the models that continue to get refined and improved on a weekly basis. It's just crazy right now.

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• 16:31Sean Carroll?

  And it's a reminder, I guess, probably as a medical doctor, you don't need to be reminded of this, but the human body is very interrelated. I mean, the fact that there is some subtle difference, even if human beings don't know what it is, between a male retina and a female retina, you know, maybe makes sense if you tell it to me, but I wouldn't have been surprised if it hadn't been there. But, you know, yeah, the body is, all the different parts are talking to each other all the time.

• 16:55Speaker 03

  That's right. Absolutely.

• 16:56Sean Carroll?

  And this is something where, again, you know, AI, is the AI able to tell us why it thinks that a certain retinal scan is man or woman?

• 17:07Speaker 03

  Well, this explainable AI is kind of an overarching goal. And sometimes, we do get a pretty good explanation, but in the case of the retina, it's still elusive. There's these things called saliency maps and masking and all these techniques that you can use to try to Kind of reverse engineer, what is this neural network doing?

• 17:33Sean Carroll?

  Right.

• 17:34Speaker 03

  But it hasn't been as a good an explanation yet provided for the retina as it has for many other capabilities that were not anticipated.

• 17:44Sean Carroll?

  Okay, perfectly fair. I guess on the flip side, there may be people who worry that their medical care is going to be handed over to computers rather than human beings. And I suppose ideally it should be both, right? There should be both in the loop and there should be interactions. But like you said with the paperwork, at least in principle, the existence of AI could give us more interactions with human beings.

• 18:09Speaker 03

  That's right. And there was something other, another thing that caught us by a big surprise recently. And my colleague Pranav Raj Perkar and I wrote an op-ed in the New York Times about it. Six studies, now there's seven, where the AI was compared to a doctor with AI for various tasks, whether it's a diagnosis or images. And the AI was better than the doctor with the AI. Okay?

• 18:41Sean Carroll?

  Wow.

• 18:41Speaker 03

  We would not have expected that.

• 18:43Sean Carroll?

  Okay.

• 18:43Speaker 03

  Everyone, including us, all anticipated that the AI and the doctor is the best winning combination. Now, what is the reason for this? Well, it could be because the AI right now isn't in high regard for doctors and so they don't really take it seriously. Or they could just have a bias against it and, or they're not grounded yet on how to use it. But it's a little concerning that the AI could have this superior performance in various medical tasks, that, you know, important task. We're going to have to see how this plays out.

• 19:18Sean Carroll?

  Right.

• 19:18Speaker 03

  But one thing for sure is, I think it's going to be imperative that all physicians learn the nuances of AI, not to immediately reject it, but to actually consider embracing it because it can help.

• 19:31Sean Carroll?

  Yeah.

• 19:31Speaker 03

  But when the AI beats out the doctors, that's a flag right there. Yeah.

• 19:36Sean Carroll?

  Right, okay, good. That is absolutely food for thought. But I would imagine that in some circumstances, like, you know, looking for polyps or nodules in some scan, if the AI could say, "Look here, it looks like there's something." Like, that could, that just sounds unambiguously helpful to the doctor.

• 19:54Speaker 03

  Yeah, the biggest study yet, you touched on one, which is the second biggest, which is colonoscopy cumulatively, but the biggest single study, over a hundred thousand women in Sweden had either the doctors, the radiologists with AI interpret the mammograms, or doctors without the AI randomized. And what was amazing, of course, is that there was this twenty some percent better detection of important cancers with the doctors who had the AI. So you would say now, in addition to other studies, that why are we doing mammograms in women without AI? Because now that's missing, you know,

• 20:38Sean Carroll?

  Yeah.

• 20:38Speaker 03

  one out of five. That's a lot of potential cancers. And we've known for years that mammography has lots of inaccuracies with false positives and false negatives. You know, there we're seeing, that should probably be universally adopted. The problem in the United States is that the company, the big radiology company that's got scans all over the country, they're charging the women extra if they want to have the AI reading, thirty five dollars or something like that. That's crazy. That should be part of a normal, and someday I guess it will, but we're in a transition zone right now.

• 21:15Sean Carroll?

  We are. Is, are the AIs that are being used, are like off the shelf GPT kind of things? Or do you need like a specially tuned medical AI?

• 21:23Speaker 03

  Yeah, it's, these are commercially available software packages, you know, that have been FDA approved now.

• 21:31Sean Carroll?

  Okay.

• 21:32Speaker 03

  The ones that are here in the US, particularly one that RadNet uses, is different than the one that was in the randomized trial in Sweden, but they're pretty similar. The point being is they, they, the good ones have all validated this twenty percent improvement of, of making the diagnosis. And so for polyps, it's similar too. The gastroenterologists miss lots of polyps, you know, like about twenty percent. So the fact that AI can, you know, give us this boost of accuracy, who wants to go through a colonoscopy and have a tired gastroenterologist who's been working all day doing this stuff?

• 22:09Sean Carroll?

  Yeah.

• 22:10Speaker 03

  Particularly, that's when it happens is later in the day, human eyes start to, you know, lose some of their... And, you know, who wants to go through all that and have a missed important Apollo?

• 22:21Sean Carroll?

  Yeah, I got that from your talk that you should always have your colonoscopy in the morning. The doctors are fresher.

• 22:26Speaker 03

  I would, plus it avoids you having a fast, you know, if you haven't got through everything another, another day. So, yeah.

• 22:33Sean Carroll?

  And maybe other than diagnostics, are there other promising uses of AI?

• 22:39Speaker 03

  Yeah, I mean, I think it's a cost of board. I mean, it's just, you name it, there's like, you know, for years as a cardiologist, we had the electrocardiogram had an overread or what do you call it, underread by the machine. And it was stupid. The readings were terrible. The error rate was really high. Well, now, not only is the error rate really impress, low, impressively low, but also what we're seeing is, is making diagnoses that were, the cardiologists might not have come up with accurately. So, for example, it can say, there's a low ejection fraction. And you say, what?

• 23:21Speaker 03

  And in fact, Mayo Clinic has already made that a routine for all of their ECG AI interpretation. But also things like, there's a risk of developing atrial fibrillation, even though there's no atrial fibrillation in this person.

• 23:36Sean Carroll?

  Okay.

• 23:37Speaker 03

  And there's a risk of stroke or this or that, kind of like the retina. So not only have we got rid of the error rate, that was kind of a major deal, but we're getting all this opportunistic readings that we never had before.

• 23:53Speaker 03

  Just a pretty, again, you know, I just don't see, don't expect this kind of thing. And it's just happening.

• 24:01Sean Carroll?

  And how prevalent is it right now for these kinds of things? Is it yet to ask special and pay or is it already there?

• 24:08Speaker 03

  The ECG is not anywhere else that I know of yet, except for Mayo Clinic. I hope it will be universally used because it's a sense that, Sean, that we're just leaving all this stuff on the table. You know, that all these extra bonus interpretations that could be useful for a patient. They should be of no charge. It's there, you know, it's, it's in the, it's in the data. I just, we need the AI to extract it.

• 24:36Sean Carroll?

  Well, well, tell me, as a, someone who's been around for a while, do you get the feeling that practicing clinical doctors are open to these kinds of changes in general? Are they, are they looking to be on the cutting edge? Or is it that they have a way that works and are kind of happy with that?

• 24:52Speaker 03

  Well, the older ones like me are usually not too receptive. Younger digital docs, you know, they kind of grew up in this environment. They're apt to be a little more willing, but overall, there's not an embracement eager to adopt AI. And it's because of the other concerns, like the, what is this going to do with errors, hallucinations and privacy and security and biases, which we know exist. Or, you know, there's many things that are, that are deterrents. Perhaps the one that I think that doesn't get enough emphasis is you really have to have compelling data to get the medical community to move.

• 25:36Speaker 03

  And the only compelling data we have that really compelling is what we're seeing with the mammography, colonoscopy, perhaps, you know, certain things where, you know, that it's just unequivocal benefit.

• 25:49Sean Carroll?

  Okay.

• 25:50Speaker 03

  But, but a lot of the things that we're seeing evidence of, they're still looking for the, the proof points that are just so clear cut that it would be considered below the standard of care, which is kind of a bit nebulous term. But it's changed when the needle is moved, when the stuff, the, the data evidence is just overpowering.

• 26:13Sean Carroll?

  Well, it does seem to me like having better diagnoses of cancer or heart disease would help me live longer, which provides a natural segue into our next big topic, which is your new book on aging. And again, let me just start at the very highest level. Aging and especially extending human lifespans, this is a topic that gets a lot of talk. A lot of the talk is maybe not reliable. I mean, how do you feel wading into this area?

• 26:42Speaker 03

  Yeah, I felt, Sean, I had to wade in because the pseudoscience and the false claims are totally out of control. And basically, it's kind of predatory, all these anti-aging supplements and, you know, stem cell clinics and, you know, peptides. And I mean, you name it, it's just so much malarkey, so much hype of false, you know, you could say some of this is fraudulent. It's a shame. And it basically is playing into the interest that people not just want to live longer, but live longer healthier health span. And that's why I decided it was time for me to go deep on this and write a book, which is Super

• 27:27Speaker 03

  Aged, which is trying to set the record straight, to really put the excitement in context. And it isn't about reversing aging amazingly. It's about extending health span to quash age-related diseases. So basically, what this is doing is taking the science of aging, which is formidable, big advances, and using that not to come up with some magical potion, which doesn't exist for people, but rather to use those advances so that we can take the big three. Heart, cancer, and neurodegenerative, mainly Alzheimer's,

• 28:11Speaker 03

  how we can apply these advances in science of aging to prevent these three major killers and major causes of losing one's health span.

• 28:22Sean Carroll?

  And just to be super clear, you know, on the podcast, sometimes we talk about very science fiction-y topics. So your focus is not on genetically engineering human beings so they live for 10,000 years. You're really thinking about, you know, how we can just live a few more years in a more healthy way.

• 28:39Speaker 03

  Yeah, I mean, as I go through in the book, if you were to really work on this, you could eke out seven, perhaps even 10 years of health span. Health span, meaning freedom from these three major diseases, age-related diseases. So, yeah, that's exciting to me. It's not, we're not talking about a few weeks or months. We're talking about years. And the fact is that we don't need a magic potion to do this. As we'll get into, we need lots of data on a person and we need AI. And we need to use the advances, which are basically these clocks, molecular clocks. That's perhaps the biggest thing that's

• 29:21Speaker 03

  a shakeup in medicine that people don't realize right now, biomarkers and clocks. And that's what's given us this newfound potential.

• 29:29Sean Carroll?

  Well, let's get into that right away. I mean, where does human lifespan come from? It seems clear from even the most obvious data that people tend to live a certain amount. And if they don't have something terrible happen to them, then they're going to die. It's not an exponential falloff, right? It's not like the same number, fraction of people die every day. Our biology gives out after a point. Probably we can guess at evolutionary explanations for that, but maybe give us a clue as to what's going on.

• 29:58Speaker 03

  Well, everybody used to think it was the genes, and that was deterministic. And that turns out to be completely wrong. While it may be an issue in a very limited number of people, it's not really about our genes. And so, a lot of this is...

• 30:16Speaker 03

  It turns out it's a multi-dimensional, complex story about why we don't just have this what's called compression of morbidity, where you live perfectly healthy and then you just fall off a cliff. You know, that's just, it doesn't work that way. Yeah. The way it works is, you know, at some point, you're going to start to see some frailty, some decline in capabilities, like whether it's cognitive or other. And so the point being is, how can we extend that, you know, intactness, lack of this compromise or frailty?

• 30:58Speaker 03

  And so what is the determinant of that? Well, we studied 1,400 people who we call the Welderly, and they had been over 85 and never been sick. They had none of these diseases. And what was interesting, we sequenced all their genomes, whole genomes. We found almost nothing from that. That is, the genes were from the story. And the protagonist patient of mine in the book, Mrs. LR, she's 98, and she has never been sick. I mean, I saw her for a trivial thing as a patient. But what's fascinating is, all of her relatives,

• 31:39Speaker 03

  her brothers and sisters, her parents, they all died in their 60s, 50s. She's 98, okay? So that's basically the story. It's not the gene. So like for me, I have terrible family history. Right. But when I, as the more I've learned about this, the less worried I've been about that most of us have this overhang throughout our lives. Oh, my, my father had this, my mother had that, whatever. That, we don't need to succumb to those thoughts, because there's so much we can do now to find out our risk.

• 32:12Speaker 03

  Individual at the individual level and that's what's a sharp contrast to the way we used to think about this in the in the past.

• 32:20Speaker 00

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• 32:47Sean Carroll?

  So specifically in this study, you had these people who were living long and they were healthy and I presume that you were hoping to see, oh, they all share this gene or at least many of them do, but in fact, essentially no connection whatsoever.

• 33:02Speaker 03

  Just about no connection. I mean, certainly nothing that was had a lot of weight. So we were surprised. We were very disappointed at the time, but now in context, it's starting to come together that we have to have a rethink about the gene story because it just doesn't really click. There may be something to it if you're over 110. There's not too many people like that.

• 33:30Sean Carroll?

  I'll get to that point, yeah.

• 33:31Speaker 03

  Yeah, they're called supercentenarians, but there's so few of those that, yeah, and even that's questionable.

• 33:37Sean Carroll?

  But is there something to the idea that, you know, once we're past our reproductive age, evolution is done with us and it sort of lets us decay?

• 33:45Speaker 03

  Yeah, we're in steady decay mode sadly.

• 33:49Sean Carroll?

  Yeah.

• 33:50Speaker 03

  So what happens is for these three diseases in particular, it takes 20 years for them to take hold, incubate, if you will. So you don't have a heart attack without having your arteries getting clogged up with atherosclerosis for two decades or more. Cancer, you don't just all of a sudden show up with pancreatic cancer. This has been developing over more than two decades. These clones and their ability to eventually proliferate and spread throughout the body. And the same thing is for Alzheimer's. We now know it's 20, 30 years you could predict ahead of time. If that is going to be a risk.

• 34:29Speaker 03

  So these processes of our deterioration, the good thing is they're really slow. It gives us a great opportunity to get ahead of them. Imagine if they, you know, took place over months or a year. And then, of course, we wouldn't have that anticipatory runway to work with. So we're really lucky in that respect. And it's that combination of these long lag time periods and the tools that we have today. That's making this exciting opportunity going forward.

• 35:00Sean Carroll?

  So you mentioned the big three. Let's, let's dig into them a little bit more. Probably if you ask people on the street, what are the three big diseases that will end your life? They probably would have come pretty close to saying like cancer, heart disease, brain diseases. Are they related? Are they all completely different causes? What do we know about why these things start kicking in at a certain age?

• 35:22Speaker 03

  Great question. There is a common thread besides the fact that they each take 20 plus years. And that thread is the immune system and inflammation. So our immune cells can secrete all these, what's called cytokines, chemokines that are inflammatory mediators. And so what's the problem with the three diseases is that they all have a marked untoward inflammation. So inflammation in our artery wall or in our brain or the immune system not responding to the appearance of a, of a tumor cell or tumor clone. So it's our immune system is the.

• 36:07Speaker 03

  Is the real problem for the three diseases. And that's one of the big deficiencies we have right now. We don't have a way, like you can go to the lab and get a blood count kind of thing. You can't get an assay to tell you what is the status of your immune system. And we really, we really desperately need that. That's like the next frontier. And people say the brain is really complex. Well, I got to tell you, the immune system is right up there. It's, it's very, you know, I have a whole chapter about that in the book. And what's exciting, of course, there is we're learning about how to rev it up and, and tone it down, suppress it like never before.

• 36:47Speaker 03

  So if we can start to get a routine way, people can get their immune system and inflammation markers assessed, that's going to give us even better ways to prevent these diseases.

• 37:01Sean Carroll?

  We did recently do a podcast with James Allison.

• 37:04Speaker 03

  Ah, yeah.

• 37:05Sean Carroll?

  About using the immune system to fight off cancer. So this, this fits in very well, but let's assume that some of our listeners didn't listen to that episode yet and maybe explain more of the details about how our immune system is supposed to work when everything's going well.

• 37:18Speaker 03

  Well, you know, that breakthrough that Allison had for immunotherapy was just the beginning of now a chain of many discoveries. And the point is, is that it's pretty hard to get cancer spread around the body if your immune system is completely intact. A cancer tries to hijack cells and suppress your immune system, but it's hard to get it rooted if, if your immune system is, is really high integrity. But the other thing we've learned is that as we keep adding more different ways of, of revving up the immune system in people with cancer that aren't responding to the, the current therapies, we keep getting more successful of getting cures.

• 38:02Speaker 03

  So it's almost like we can't do enough with personalized neoantigen vaccines and tumor infiltrating lymphocytes and conjugate drugs. All these things are basically trying to get the immune system to go into high power mode, you know, and that's a big learning. And the point being is if, if I could say, well, let's say you, Sean, you have this significant risk of cancer in your lifetime. What I'd be doing is maybe every year assessing your immune system. And when it was showing signs of showing a bit of what we call immunosenescence, you know, aging, we would give you something like a vaccine, like we were talking about

• 38:45Speaker 03

  at the, you know, the, the shingles type vaccine, but we might give you a vaccine just to give you a higher gear of your immune system so that you are in defense mode.

• 38:56Sean Carroll?

  Yeah.

• 38:57Speaker 03

  And of course, we don't want to go too exuberant because we don't want you to go into self-attack mode either and develop an autoimmune component at all. But that's where this is, the, the, the cancer story that's unraveled since the great work of Allison and others is really built on the fact that it's really an immune system defect that's allowing cancer to, to, to take hold and spread in our body. And we have got to prevail over cancer. This is a fundamental goal. We've been talking about this moonshot and, you know, for years, for decades, but now there's a, there's a way to see through it.

• 39:41Sean Carroll?

  So tell me more about the cellular biology here. I understand that there's like T cells involved. What is supposed to be happening in my bloodstream when I, when my immune system is going great guns?

• 39:53Speaker 03

  Well, there's a lot of different components. The B cells that are known, of course, they're, they're making the antibodies and the T cells that are kind of a primary way that we can kill cells that are, that are troublesome, that are foreign, have foreign proteins on their surface. And of course, there's so many other aspects of, you know, interferons and there's regular neutrophil white cells and there's natural killer cells and it's a big system.

• 40:23Sean Carroll?

  Okay.

• 40:24Speaker 03

  It comes down to when you, when you're trying to deal with cancer as an example. You really want to have the ability to recognize these foreign antigens on surface of cells, the cancer cells. And that's where the T cells really kick in. And so what you can do now, which is really quite extraordinary, we've seen, like, never seen before, a small numbers of patients, but refractory cancer, they failed every therapy, kidney cancer, pancreatic cancer. They had the kitchen sink of everything we got, and they couldn't respond. And then they got a so-called neoantigen personalized vaccine for their cancer. That

• 41:08Speaker 03

  is, they were, the cancer cells, they looked at these antigens taken out of the body, and then engineered T cells to fight them for that person's specific cancer. And guess what happened? I mean, that was like melted away. I mean, just, now, the problem, of course, is it's not something that you could scale in millions of people who have cancer each year around the world. But on the other hand, if we can get off-the-shelf ways to do this, that's where the prospects lie today, is that we don't want to have to necessarily make T cells that are individualized, but rather if we can come up with the common

• 41:52Speaker 03

  antigens or proteins that are the responsible, that that can stimulate our immune system, that's what we want to do.

• 42:00Sean Carroll?

  And, well, I don't know. I mean, can we imagine some combination of AI and DNA robots, and I don't know, that will sort of fix up our immune system in a kind of bespoke way for whatever it is that we're most in danger of?

• 42:17Speaker 03

  I wouldn't rule it out. Certainly possible. I like your thinking. It's futuristic and you're bringing all this stuff together. I'm more kind of looking at the here and now potential, but you're right. Already AI is being used to determine the matchup of the person's antigens of their tumor cells and the T cells. We're already starting to rely on AI because in any given cancer, there's hundreds and hundreds of these particular proteins. And so the finding the ones that are to develop a vaccine against is you don't, you can't do it against hundreds. You got to pick

• 43:00Speaker 03

  the most important ones and AI is helping to do that.

• 43:03Sean Carroll?

  Okay, good. And I think I do see what we're talking about here vis a vis cancer, especially because we did talk to Jim Allison before. So what's the analogous story for cardiovascular disease, neurodegeneration?

• 43:18Speaker 03

  Yeah, so the Alzheimer's story is, a lot of people don't realize this, how extraordinary change there is. So there's a blood biomarker called PTOW 217, and there's a couple others like it. And basically, what they are is as good as a PET scan for the brain. Okay, so you just have a simple blood test, it's available, it tells you your risk of Alzheimer's. And by the way, if you're, if that marker is high abnormal, and you get another one in six months or a year, then you can say exactly when you might get mild cognitive deficit. So it stages the disease, no less makes the diagnosis of risk. Now, and just so, it used

• 44:03Speaker 03

  to be, we have a genetic test, and we'd say, oh, well, you have a higher risk of Alzheimer's. And we didn't know if it was at age 98 or 68. Now we know, you know, right, very precise, timing, not just the extent of the risk. Now, what's amazing here is that you can do all these things that reduce inflammation in the brain.

• 44:27Speaker 03

  Which we didn't know before. So like, for example, diet and exercise, the right kind of diet and the right kind of exercise can really help reduce inflammation in the body and the brain, lifestyle factors.

• 44:41Sean Carroll?

  Okay.

• 44:42Speaker 03

  But also, what's really intriguing right now is all these GLP-1 drugs like Ozempic and Mounjaro, they reduce inflammation in the brain. It's one of the most important ways that they work. So that they're being tested now to reduce Alzheimer's in big trials that are due out in less than a year. So there are other ways to reduce inflammation. The point being is that you might have some amyloid plaque in your brain, but if you are, if your brain is reacting to it and it's inflamed, that's how that's the ticket to developing.

• 45:19Sean Carroll?

  Okay.

• 45:20Speaker 03

  Alzheimer. So knowing your risk and getting all over it with the lifestyle of preventable factors and likely drugs in the future, not the kind of drugs we have right now that are used for people already have Alzheimer's, that are dangerous drugs and don't work very well. But this is the ability to prevent Alzheimer's in the future, which is really quite remarkable.

• 45:45Sean Carroll?

  I don't know a lot about Ozempic, the weight loss drug, or it's usually marketed as a weight loss drug, but I, I keep hearing how, oh, it has this extra unanticipated good side effect, which is kind of the opposite of what I'm used to hearing about all the deleterious side effects. Are we learning more about why this is so awesome? Does it have something to do with the immune system?

• 46:07Speaker 03

  Yeah, I mean, I think what's fascinating here, that if you take these drugs, it's so-called GLP-1 drugs, they don't get into the brain very well. So people started to wonder, how do you see such great reduction of brain inflammation? No less, you know, how do you see the reduction in appetite and desire for healthier foods and, you know?

• 46:31Speaker 03

  Basically completely rewiring your reward circuits.

• 46:34Sean Carroll?

  Yeah.

• 46:35Speaker 03

  And it turns out the gut-brain axis. So basically, it's affecting the gut. There's a vagal nerve that connects the gut to the brain. And it's through this circuitry that basically the brain is kind of the master regulator of our inflammation, both in the brain and throughout the body. Which we only learned about that in the last couple of years. You know, we thought it was just the blood, but no, the brain's talking to the blood and the gut's talking to the brain. And so this is what is we're learning about these GLP-1 drugs that have had more impact across more diseases, some of which have nothing to do with weight loss.

• 47:17Speaker 03

  The inflammation is reduced before anyone loses weight. Okay, so this is this is a whole new day for understanding these inter-organ connections.

• 47:32Sean Carroll?

  And, okay, and then heart disease. This is your thing, right? I mean, it does sound different than the other two. Like, heart disease seems more sudden, or maybe that's just my misimpression?

• 47:41Speaker 03

  Yeah, people think, oh, I had a heart attack and this was sudden. No, no, it's been brewing for at least 20 years. We have seen autopsies from 20-year-olds, 30-year-olds, that they already have plaque building up in their arteries, in the heart arteries, the so-called coronary. So, no, this is something, the only sudden event is that finally there's a crack in the plaque. But that plaque has been growing and kind of inflamed. And here's another point is that if it wasn't that the plaque got inflamed, you wouldn't have a heart attack. And that's in part why statins work. They not only lower the LDL, but they reduce inflammation. They're not as powerful as GLP-1 drugs.

• 48:24Speaker 03

  But statins and anything that reduces your LDL cholesterol will also reduce some inflammation for those for the arteries. Because those are those are a species of the fatty proteins in our in our blood that the artery does not like that, having it in their wall. It just reacts to it. And so years and years of accumulation of bathing your arteries and

• 48:51Speaker 03

  Bad cholesterol, LDL, and now there's another one that will become routinely measured and new drugs to fight against called LP little a, which we never had anything for it, but now we are seeing five different drugs that are emerging to tackle that one. So this is exciting, too, that, you know, we're, we're coming up with new ways to prevent the, the toll of heart disease. People don't die of a plaque. They die of heart attack or a stroke for the arteries that go up into the brain.

• 49:25Sean Carroll?

  Sometimes informally, people talk about dying of old age. Is that a thing? Or is that just like a catchall term for your immune system not doing what it's supposed to be doing?

• 49:35Speaker 03

  You don't die just of old age. You gotta die of something, right? Because age itself isn't the killer. So there's got to be something else like explaining it. Could it be heart rhythm problem? Could it be, you know, um, you know, something that doesn't get diagnosed? An indolent infection, you know, many, many possible things, but you don't die just of old age.

• 49:59Speaker 05

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• 50:43Sean Carroll?

  There is the idea that one's telomeres decay, right? As, you know, cells divide, our genetic code is sort of being eaten away from the ends. Is, how relevant is that?

• 50:54Speaker 03

  Well, there's a lot of things happening as we age. Our telomeres, which the end of our chromosomes, they get shorter and shorter. But there isn't a good way of lengthening them or lengthening them safely because they're also connected to your propensity to develop cancer. You don't want to muck around with them. And they're not nearly as good as the new clocks for telling you about your aging. So the new clocks, they include organ clocks. So what's amazing here is I could get a blood, tube of blood from you and I could check, it's kind of like going to your car for every system, right? It would tell me about your aging of your brain, your heart, your kidneys, your liver,

• 51:39Speaker 03

  your immune system, eight systems of your body from a tube of blood to say, is that organ in you aging faster than your chronological age, your actual age?

• 51:52Sean Carroll?

  I see, okay.

• 51:53Speaker 03

  And then I say, you know what, Sean? I gotta get all over this risk for your heart. And I'm gonna check these other things. I'm gonna, you know, confirm that this is it. And now this is what we're gonna do for you. So you never, first of all, we're gonna slow your heart aging. We're gonna slow it. Here's how we're gonna slow it and we're gonna measure it again to prove that we slowed it. Okay? That's what's so different today. We didn't have organ clocks.

• 52:20Sean Carroll?

  Yeah.

• 52:21Speaker 03

  We didn't have epigenetic clocks that tell us our body-wide aging relative to our actual aging. We have all these ways to detect whether someone is, not just the person, but the organ is off track.

• 52:39Speaker 03

  And it's, this is the science of aging crystallized to make a difference.

• 52:44Sean Carroll?

  That's great. Yeah. And I do want to get into sort of the nitty gritty of what an individual can do to, you know, live longer and more healthy, but maybe we can sweep the deck of some of the crazier ideas out there first. I mean, if I got a blood transfusion from, you know, children's blood or something like that, would that clean out my system and help me live longer?

• 53:07Speaker 03

  Yeah, there's a lot of these things that are out there, certainly in mice and animals, that if you take old, young blood plasma and put it in old, you can see some improvements in metrics. In people, it's never been established that it's safe or effective with any durable impact. And it's a very expensive procedure called plasma foresis that these clinics, particularly out here in California.

• 53:38Sean Carroll?

  California, exactly. Yes.

• 53:40Speaker 03

  Horrible. But they're around the country too. They're even in other countries. It's shameful because there's no data and, you know, very, this is not covered by any insurance. This is really expensive. And this is for the likes of these extremists. Like Brian Johnson, the guy who had the Netflix special who takes hundreds of supplements a day and has, you know, a penile sensor and not eating. I mean, this guy, and he had his blood transfused from his son. You know?

• 54:09Sean Carroll?

  Well, yeah.

• 54:10Speaker 03

  This is crazy stuff. And he's kind of the one, this don't die. He's promoting this stuff and people believe it, which is, which is a shame.

• 54:19Sean Carroll?

  When a 200-year-old person starts promoting that, I'm going to start believing them. But until then, I'm going to be skeptical. But I was, I was shocked to learn recently that the supplement industry in the United States is several times larger than the entire prescription drug industry.

• 54:37Speaker 03

  You know, that's a really sad fact. As far as I know, it's true. And a lot of it is anti-aging.

• 54:44Sean Carroll?

  Yeah.

• 54:44Speaker 03

  You know, I, I, the other day I was in the airport in Oakland and there was a vending machine of anti-aging supplements.

• 54:54Sean Carroll?

  Wow.

• 54:55Speaker 03

  And I said, wow, I mean, wow, what are we doing here, right?

• 55:01Sean Carroll?

  Well, I happen to know that the anti-aging supplement industry is very fond of advertising on podcasts. So I, I don't do that. I don't actually, I, I turn those down, but uh, they're all over the place.

• 55:11Speaker 03

  The sad truth about that is that these longevity, so-called longevity doctors and scientists, they're the ones that are hawking the supplements. Horrible. None of them are proven and they're not, you know, they're not only lack of efficacy, but they're also questionable in safety. And of course they're a big dent in your finances. Everything bad about it, everything.

• 55:34Sean Carroll?

  Okay, good. We, so you've gotten that off the deck a little bit. Uh, I, I guess there's things we can do individually and things we can do as a society. I mean, let's talk about it as a society first. One cause of death is just, you know, a pandemic or an infectious disease or something like that. I mean, how, how good are we at? I know this is a politically charged question right now, but how good are we these days at protecting against future pandemics?

• 56:02Speaker 03

  Not good. And the problem here is, you know, obviously we didn't do well for the COVID pandemic, but we haven't learned the lesson. So instead of, you know, taking advantage of the things we learn, we're seeing gutting of our resources in the United States. I mean, unbelievable takedowns of the programs at CDC, NIH, FDA. So this anti-vaccine, anti-science culture. So we're, we're actually in much worse position than we were for COVID because of this. Movement against science and it's a shame because we learned a lot of what it takes to be

• 56:47Speaker 03

  ready and now even with threats that are out there whether it's avian flu or or you know others that we know are potential pandemic threats there's there's reluctance there's denialism to confront what we should be doing and it's really sad.

• 57:09Sean Carroll?

  Do you find yourself personally involved in political discussions or strategic discussions? Or is it something where you know the all the scientists are already on one side? We sort of don't have to talk to them.

• 57:21Speaker 03

  Yeah, no, and then the problem is that the people who are running the show now you can't reason with them.

• 57:29Sean Carroll?

  Yeah.

• 57:30Speaker 03

  Because they were now empowered to take apart the systems that we had. And so we're kind of in this auto destruct mode and you're trying to whether you're dealing with measles and you say you got to get everybody vaccinated and you know this is our best protection and what you're hearing is take cod liver oil and vitamin A.

• 57:52Sean Carroll?

  Vitamin A, yes.

• 57:53Speaker 03

  Have children in the hospital because of liver toxicity that has nothing there's no data to support that for preventing measles, but there are data obviously for the toxicity of taking these at high doses is really this is a sad state. We're going backwards. It's almost like we're going in the dark ages here.

• 58:16Sean Carroll?

  Yeah, I figured that was true. I figured it was nevertheless important to get it on the record there. So thanks for that update. Let's instead ask questions about what you and I can do a little bit. I mean, you have a really interesting section of the book where you talk about lifestyle plus explain what that is.

• 58:34Speaker 03

  Yeah, so we used to think lifestyle was all about diet, exercise, and then more recent years, sleep health. Turns out there's missing about ten other layers of lifestyle. They extend through things like ultra-processed foods as a component of diet, no less the protein component. And all the details of not just food, but also beverages, you know, alcohol and all that, caffeine. But then, as you get into other layers like exposure to air pollution, microplastics, forever chemicals, social isolation, time in nature.

• 59:18Speaker 03

  I mean, it's a long list of what we would consider lifestyle plus. You could say lifestyle, environmental, socioeconomic, you know, all these other factors, but it's hard to, it's too many syllables and words. So I just call it plus, you know?

• 59:35Sean Carroll?

  So, okay, I mean, that's just, I know that some of these are kind of cliched and everyone is supposed to know them. What is a healthy diet? And if for specifically aimed at the goal of being healthy and active for more years?

• 59:49Speaker 03

  Yeah, so this is really topical because very recently there was a study, thirty years of follow-up of over a hundred and five thousand people. And only nine percent lived to age seventy without the chronic diseases we've been talking about. Age-related chronic diseases, the big three. And so they could, they could zoom in on what did they eat? What were these nine percent were different than the rest of the folks? And what was fascinating is it just confirmed everything we knew at this powerful study. Fruits, vegetables, the Mediterranean-like diet, reduction in, you know, red meat, animal fat,

• 1:00:34Speaker 03

  ultra-processed foods. So it was confirming everything we've known, but now in a whole new study. And it's called the optimal diet for healthy aging. So I that's one thing. The other point about it is um we don't as we get older, we don't want to be light on our protein intake, but we don't want to be too heavy either. If you take too much protein, which you got to work at getting, but there's at least some people out there advocating these super high protein diets. Wrong, because that promotes inflammation and promotes atherosclerosis. So um you you you don't necessarily want to be at the the recommended dietary allowance

• 1:01:18Speaker 03

  of point eight grams per kilogram. You want to be maybe around one point two, but you sure don't want to go to, you know, two point O or higher, which is what um some of the people out there have been without data, you know, to to preserve your muscle mass as you age. But then you go into other things like, you know, what type of exercise? The resistance training is really important. And it doesn't mean there's no such thing as 10,000 steps, you know, it's like no one ever there's you even less than that, you even weekend warrior exercise is great. And then sleep, the sleep thing is wild because we always to always think that, you know, how many hours did you sleep? No, it's about how much deep sleep

• 1:02:03Speaker 03

  you got, which we which is reduced with aging. And also people take drugs like Ambien, which backfires.

• 1:02:12Sean Carroll?

  Okay.

• 1:02:13Speaker 03

  They they sleep, but turns out that sleep is how you get rid of all your toxic waste products in your brain that promote inflammation. So if you take Ambien, it what's amazing is you sleep more, but it blocks the efflux of these toxic um chemicals from your brain. It's like the worst thing you could do.

• 1:02:39Sean Carroll?

  I didn't know that.

• 1:02:40Speaker 03

  Probably extends to all the other drugs because that's the only one that's been carefully studied.

• 1:02:45Sean Carroll?

  So I knew that I knew that sleep helped sort of rewire the connections in our brain a little bit, but I didn't know that it was literally cleaning out toxic chemicals.

• 1:02:54Speaker 03

  Cleaning out. That's what it's all about. And so you don't get deep sleep. It's actually extraordinary. Uh, and there's interactions with our heart rhythm and the, and the efflux of the, these ways. But drugs don't help at all. They, they seem to make things worse, especially the one that's most commonly used. So you can learn. How do you get better deep sleep? You know, you can, you get a smart watch or a fitness band or, um, you know, the aura and other rings. And you can, you can train yourself.

• 1:03:28Sean Carroll?

  Okay. So that's, that's crucially important. So say more about that. So like, uh, cause everyone says sleep is good. I like sleep. It sounds good to me, but this, the fact that the drugs are counterproductive. And nevertheless, I can train myself in what, what sounds like a more natural way, actually. And that the smartwatches are actually helpful. That, that sounds important.

• 1:03:48Speaker 03

  Yeah. Because turns out if you start tracking it, like I've done. What you can see is eh, I had terrible, you know, amount of deep sleep. And of course it does reduce as you age and men are generally less than women. So I was kind of in a high risk group to start. But what was interesting is by trying different things. Uh, I could see, oh, wow, I'm getting more and more and more deep sleep. So for example, I never was trying to go very precise about, you know, when I was going to go to bed each night. And, you know, try to get into as close to a ritual as possible. That makes a difference. You know, your clock, your biologic clock.

• 1:04:29Speaker 03

  Other things like, you know, attending what, what exercise you're doing, what, what you're eating. How late in the day you're eating and so, you know, so many things, interactions that you could start to. See the pattern without AI and with AI, of course, it'd even be better. Uh, we don't have that yet, but we will. Any rate, um, each person can learn about, um, getting better deep sleep and it's really important.

• 1:04:58Sean Carroll?

  And, um, I, I don't want to skip over something you mentioned already, but it's worth emphasizing, which is the ultra-processed foods. Like that's something that's hard to avoid in the United States of America in the year 2025.

• 1:05:11Speaker 03

  Hard to avoid, but easy to reduce.

• 1:05:14Sean Carroll?

  Okay. Well, what counts as ultra-processed?

• 1:05:18Speaker 03

  Oh gosh, anything that you don't have in your kitchen that's nor, you know, normal ingredients for, you know, good home food. Um, so you can tell pretty, you, you kind of do a smell test or a sight test. If you look at a package and you see lots of ingredients, that's a bad sign.

• 1:05:37Sean Carroll?

  Okay.

• 1:05:39Speaker 03

  And there's different types of ultra-processed bad things. There's some of these are emulsifiers, like, you know, xanthum gum and, but if you don't recognize this stuff,

• 1:05:49Sean Carroll?

  Yeah.

• 1:05:49Speaker 03

  it's bad. It's bad. And what, again, it goes back to that theme we've been talking about is promoting inflammation in our body, no less our brain, and putting us at risk. There, it's like the opposite of what we've been talking about is increasing the risk of the big three age-related diseases.

• 1:06:08Sean Carroll?

  Yeah.

• 1:06:08Speaker 03

  Now, the average American takes in 60% of their food is ultra-processed, which is the highest in the world.

• 1:06:15Sean Carroll?

  I'm sure.

• 1:06:16Speaker 03

  And, uh, a friend of mine who wrote a book, Ultra-processed People, Chris Van Telekin, who's a UK physician scientist, he, he did a 30-day test of maximizing ultra-processed food intake and a brain scan before and all these inflammation markers. And what happened was, you know, he gained, uh, 20 pounds. He had big-time inflammation in his brain in 30 days of this. And he had all these off-the-charts inflammation blood tests. So, the point being is that it makes you eat more, it creates much more inflammation. And if

• 1:06:55Speaker 03

  you just are careful about what, you know, the food that you intake, and includes beverages that they have added stuff in them, particularly, um, then you can reduce this. It's not hard to get it down to 20 or 30% instead of 60 or 70%.

• 1:07:13Sean Carroll?

  And the feeling?

• 1:07:14Speaker 03

  Kids eat, it gets them to 70 or 80%. Their diet. Yeah.

• 1:07:19Sean Carroll?

  Do you have strong feelings about what are marketed as nutrition bars? Like, you know, these little bars that have everything good for you in them, but it seems like they're probably pretty processed.

• 1:07:28Speaker 03

  Most of them are horrible.

• 1:07:30Sean Carroll?

  Okay.

• 1:07:30Speaker 03

  Horrible. You look at them in degrees. The other day, a person gave me one that I said, oh, wow, this one's pretty good. It was, you know, just truly natural, nothing added. But you have to really read the labels and some of them that are widely used, uh, marketed. That you think, oh, these are great. Just, just be open minded because you'll find that those labels are, the good thing is that labels exist.

• 1:07:57Sean Carroll?

  Yeah.

• 1:07:57Speaker 03

  And the bad thing is they got lots of ingredients that you don't recognize.

• 1:08:02Sean Carroll?

  Okay. All right. Eat a carrot, I suppose. I guess I'm not going to be surprised.

• 1:08:06Speaker 03

  Carrots are great.

• 1:08:07Sean Carroll?

  Yeah.

• 1:08:09Speaker 03

  And fruits.

• 1:08:11Sean Carroll?

  So, okay, I mean, even though it is obvious, this is very, very good to be reminded. It's not obvious, but it's, it should be well known that eating better alcohol not actually good in anything other than the tiniest of doses, right?

• 1:08:25Speaker 03

  Yeah, I think there's a lot of debate about that. The question is, what is a moderate dose, right? You know, I recently had a patient and his wife are seeing them. And just before we were wrapping up, the wife said to me, is it okay if he has, continues his moderate drinking? And I said, well, what is the moderate drinking? And he, and she said, well, he has two tequilas and six beers each night.

• 1:08:53Speaker 03

  I thought she was joking with me.

• 1:08:54Sean Carroll?

  Yeah.

• 1:08:55Speaker 03

  He was joking with me. Well.

• 1:08:58Sean Carroll?

  That's a lot.

• 1:08:58Speaker 03

  Yeah. So the question is, what is moderate? And, you know, if it's two drinks on each of a weekend day, you know, because it's helped social interactions and it's enjoyable. There's probably little data to show that that's harmful.

• 1:09:15Sean Carroll?

  Sure. Okay.

• 1:09:15Speaker 03

  On the other hand, if you're drinking every day and you're having, you know, a fair amount of intake. And, you know, usually it's more than people like to admit or think. Anyway, that, that, when you start getting to high doses as you've, as you pointed to, that's a problem.

• 1:09:33Sean Carroll?

  And I guess the other thing to sort of wrap things up, the other thing that struck me in the book was your talk about mental health and social interactions. You have a very vivid graph that you reproduced that basically, if I read it correctly, says after age 60, people are either alone or they're with their partner and they don't interact with other people that much.

• 1:09:54Speaker 03

  Yeah.

• 1:09:55Sean Carroll?

  And that's a contributor.

• 1:09:57Speaker 03

  Absolutely. And it got worse during the pandemic. People just living in a cave, especially the older, the more likely. But it's still a big problem that anedated the pandemic. And this is really bad for your health, really, as it turns out. The connection of that with bad outcomes is striking. So for mental health, but it's obviously, as you well know, everyone knows, there's a lot of interactions between our mental health, our stress and our physical health. And for mental health, with the more social interaction, the less isolation, the aversion to loneliness, these are really important things to strive against.

• 1:10:41Speaker 03

  That, again, going back to that feature patient of mine, she has, you know, she plays rummy cube for every, every week with eight of her friends.

• 1:10:54Sean Carroll?

  There you go.

• 1:10:55Speaker 03

  All in their 90s, you know, and that's a good thing. And she, you know, frequently interacts with other people in her retirement community building. So these are things that are really much more, they seem like social science, but the data are striking and so we really should pay attention to it.

• 1:11:15Sean Carroll?

  Is there any truth to the idea that if I just, if I solve puzzles, if I do the crossword puzzle, if I keep my brain active in that way, play video games, read novels, does that help at all with aging?

• 1:11:27Speaker 03

  Well, that's an interesting question. You know, the studies are mixed. There's a new one coming out that says the more you work as you get older with technology, like iPads and computers, it's actually better, you know, which is interesting.

• 1:11:43Sean Carroll?

  Okay.

• 1:11:43Speaker 03

  But brains, just like humans are meant to be interactive,

• 1:11:51Speaker 03

  as a social, as we are really a social animal, even though people like to not be that way. The same thing is stimulating the brain has got to be good for it. Proving it is tricky because, you know, the, we didn't have the right tests. Like, for example, what I'd want to know is that biomarker we had for Alzheimer's, which is, can it be improved by exercise and diet? I want to see that biomarker go down with this brain stimulation.

• 1:12:22Sean Carroll?

  Yeah.

• 1:12:23Speaker 03

  No, no studies like that have yet been done.

• 1:12:26Sean Carroll?

  Interesting. Okay. It seems like an obvious thing to do. Why haven't they done that one yet?

• 1:12:30Speaker 03

  Because these are new. You know, we didn't have a brain organ clock until like the end of 2023.

• 1:12:37Sean Carroll?

  I see. Okay.

• 1:12:38Speaker 03

  So it's, these are studies are going to be, and then we can ice it and we can say, hey, you know what? These things are really good for you. And you know, the other thing, Sean, it might be really good for you, but not for another person.

• 1:12:49Sean Carroll?

  Of course, right.

• 1:12:50Speaker 03

  It, it, none of this stuff is like all one, one size fits all, and we have to keep that in mind, too.

• 1:12:56Sean Carroll?

  And to bring it home, that's another place where AI might be useful, right? In personalizing your regimen, whether it's diet or exercise or mental activity.

• 1:13:06Speaker 03

  That's exactly right. So that you, we would know in general the things that would help. But then by tracking these different metrics over time and people who are at high risk, the AI can say, well, this is what's working and this is what, you know, the gaps. And this is what's going to change. I call it precision medical forecasting. We, you may know this, but AI has radically changed weather forecasting. It hasn't been implemented, but now you can have ninety nine point nine nine percent accuracy in weather forecasting like we never had before. I mean, most of the time it seems like the weather forecasting is, you know, pretty far off, but that's going to be changed quickly because multiple groups have shown that now

• 1:13:51Speaker 03

  with these large language models, multimodal data, you can get such remarkably accurate weather forecasting. Well, we're about to do that for people, for their health, and that, to me, is even more important than the weather.

• 1:14:06Sean Carroll?

  Recognizing patterns, that's what they're very, very good at. And I'm sure, so we can finally all agree that listening to the right podcasts is probably the best thing that can help you live healthier, longer life, right?

• 1:14:18Speaker 03

  You got it. No, this, this has got to be the one. This is definitely stimulating the mind, so.

• 1:14:23Sean Carroll?

  That's all we can ask for. Eric Topol, thanks so much for being on the Mindscape Podcast.

• 1:14:27Speaker 03

  Thanks for having me, Sean.

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