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Chasing Life is supported by The World As You'll Know It, a podcast about the forces shaping the future. In this season, host and science journalist Carl Zimmer speaks to some of the most respected scientists in the field of aging research about the massive changes in human longevity and what comes next. Is our lifespan set or will a breakthrough add decades to our lives? Can older brains be rewired to function like younger ones?
Which so-called biohacks actually work? The World As You'll Know It is available now.
This episode is brought to you by State Farm. Knowing you could be saving money for the things you really want is a great feeling. Talk to a State Farm agent today to learn how you can choose to bundle and save with a personal price plan. Like a good neighbor, State Farm is there. Prices are based on rating plans that vary by state. Coverage options are selected by the customer. Availability, amount of discounts and savings, and eligibility vary by state. I want to start off today by introducing you to someone special.
My name is Lenore Catherine Rushall. Most people know me as Lee. Lenore wears a lot of hats. She's a doting mother and grandmother. She's an award-winning painter. I have no time to sit too long.
I'm happier when I can produce something. And she really likes to play cards. I'm the oldest one that plays the game of cards that I play, and I have friends who bring up age. Oh, I'm turning 80. Well, that's not a big number. It's how you look at it. I also consider her to be what the kids call "goals."
She's 98 years young, has exceptional physical and mental health. She does take medications for high blood pressure, but she's never had any major health conditions. No cancer, no heart disease, no dementia. In many ways, Lenore is the true embodiment of the phrase, age is just a number.
Doctor asked me if I thought I had good genes. I don't think those were too good. It's just not important what number it is. It's what you do with your life. My guest today is one of Lenore's physicians, cardiologist Dr. Eric Topol. He's been researching longevity now for decades, and he refers to people like Lenore as super-agers.
They're committed. They have a purpose. It's much more than just diet, sleep, physical activity. Dr. Topol is the founding director of the Scripps Research Translational Institute in La Jolla, California, where he leads something known as the Welderly study. Yes, Welderly. It's a term that he coined to describe people who've never developed chronic medical conditions or diseases.
He and his team studied more than 1,400 people, including Lenore, aged 80 to 105. They all fit this description of super-agers.
It isn't about reversing aging. It's about a whole different approach to preventing age-related diseases. Now he's the author of a new book called Super Agers, an evidence-based approach to longevity. In full disclosure, I've known Dr. Eric Topol for a long time. I have followed his work for decades, so I was really excited to sit down and talk to him today about why he thinks more people can live as long and as healthily as Lenore.
how it can be done, and why he says genetics actually plays a smaller role in longevity than we might think. I'm Dr. Sanjay Gupta, CNN's chief medical correspondent, and this is Chasing Life. I'm so curious about people like this because she's always been healthy, always been cognitively sharp. Did she decline from where she was? Like, was she even better at 70 years old and has declined now at 98?
That's a really good question. I mean, the first thing, of course, that I noted with her is that all of her relatives, her parents and her sibs, you know, they died young in their 50s and 60s. She does a lot of oil painting, and...
And she said, you know, my hands aren't quite as steady to do that fine detail now that I could, you know, just a few years ago. So there's certain things that have changed for her, but for the most part, in terms of her, her wit and her ability to articulate everything and,
Her enthusiasm about all that she's doing, I doubt that could have changed. It's fairly impressive. So what is it then? I mean, so you're making the case that this isn't genetics, I think. This isn't her family. Her other relatives died young or died younger at least.
What has happened with her, do you think? So one of the things that's striking about her is that she has a very good social network. They play Rummikub every week. But she also enjoys her solitude and doing these thousand-piece jigsaw puzzles and her painting.
So she has a really good balance of not being isolated, but also having hobbies. And we've learned these things, as you well know, are important. We don't give these types of things enough credit to promote healthy aging. I think part of the reason, and I struggle with this as well, but part of the reason we don't give it enough credit is because it's a little bit of a more tenuous line to draw one to the other, cause and effect.
I mean, if you lower your cholesterol, if you're a runner, if you maintain really good lean muscle mass and bone density,
you can kind of wrap your head around that. But the idea that someone plays card games or is an oil painter, how does that translate to a longer life? I mean, is she more likely to take better care of herself, more likely to follow up with the doctor, be compliant with any meds, if any, that she's on? Is that the connective tissue? That's certainly part of it. I mean, you know, she hasn't missed any COVID shots and
She has had a good relationship with her primary care doctor and certainly she's always been careful about her nutrition, about going for walks, being active. And she's a good sleeper, that doesn't hurt either. I mean, she's not doing strength training.
She doesn't really get out in nature very much. But, you know, we've learned so many things that are related, as you say, not necessarily cause and effect, but they sure track with healthy aging. And she has quite a few of those that she's been, that's been part of her life for many decades. Do you think, just broadly speaking, that someone like Ms. Rothall is an exception to the rule? Or can she be the rule? Yeah.
I think she can be the role in the years ahead. That's what I think is so exciting. But the other patient that I presented of mine who has been a patient for 35 years now,
He's the more norm today. He just turned 99 and his wife said to save the date for his 100th birthday party. So, I mean, he has been a pure cardiac issue. You know, many things like heart attack, bypass. I put in stents years ago when I was back at Cleveland Clinic and he had COVID and he was hospitalized and he got through all that. So he is resilient today.
But the difference about him, Sanjay, is that his disease was fully preventable. But we now know how he could have prevented it. We didn't know before. But look how he's gotten through all these triumphs of modern medicine.
And is just incredibly intact. And so that's another way to get to super agers. It's the more common way where you're going to have one of these diseases, but hopefully we're going to be able to prevent them. And of course, there's this other thing that we have done pretty well over the years, especially in cardiology is secondary prevention. We're much better at that than we are for primary prevention of cancer, heart disease, diabetes.
and neurodegenerative disease like Alzheimer's. We've been terrible, really, for primary prevention, and that's been a fantasy for maybe millennia. Before we move on, I do want to take a moment here to define primary prevention. It means preventing a disease from developing in the first place. Secondary prevention is reducing the impact of an existing disease to prevent progression or complications. I also want to highlight something that Dr. Topol just said.
There are two types of super-agers. The first includes people like Lenore, who reach their 80s and above and never had any chronic health issues. He says this group is actually pretty rare. There's a second type that is much more common, and these are people who've reached their 80s and above, have had one and possibly more major health conditions, but manage those conditions well and still maintain overall good physical and mental health.
And that's where the second patient Dr. Topol just mentioned fits in. His name is Ray, and in the book, he's referred to as Mr. RP. In the book, in Super Agers, you write that only about 20%, I think 19%, of over 400 centenarians managed to avoid chronic disease. That was from the New England Centenarian Study. The majority, that means developed centenarians.
comorbidities and were classified as survivors having a diagnosis of this age-related illness before 80 or delayers, meaning they were diagnosed at 80 and beyond, which I think is really interesting. And Mr. RP, who I think you're talking about, sort of fits into that category. So if genetics aren't that important in terms of superaging, how important are they in terms of developing disease?
Well, that's really a key because as we've learned with polygenic risk scores, which can be obtained quite inexpensively, they do help us as one layer, one component,
source of data define genetic risk for these three age-related diseases. But now we have all these other ways, like organ clocks, like eight organs, including the immune system and the heart and the brain, and inflammatory markers. And so with AI and the ability to process billions of data points for any person, and critically, all three of these diseases take at least 20 years.
to actually take root in our bodies. So if we can't get ahead of that with a 20-year lead time, we're not too smart. I want to pause again to explain a few terms you just heard. A polygenic risk score. That uses blood or a saliva sample to sift through your DNA to look for genetic variants that may put you at higher risk of particular diseases. Breast cancer, heart disease, type 2 diabetes.
Organ clocks. That can tell you how quickly your individual organs are aging relative to your chronological age by analyzing the proteins that are expressed in that organ. So if one organ is aging faster than the others, say your heart or your brain, it might put you at higher risk of developing certain conditions like heart failure or Alzheimer's disease or even dying early.
Both of these methods, the organ clock and the polygenic risk score, are still being developed, and they're not yet in widespread use. I want to talk about those three sort of broad classes of disease. I think you're talking about cardiac disease, cancer, and dementia. One thing, though, just comparing and contrasting Ms. Rashal and Mr. Arpi, you know, given that Mr. Arpi had some significant health challenges, you know,
Does he think of life differently, do you think, than Ms. Russell? Well, I mean, they both, and then if you go to the 1,400 that were in our study that fulfilled the criteria, they generally are very upbeat people.
You know, they're not complainers. You know, with Ray, he's interesting because he has a wife that really looks after him in terms of, you know, all the kind of lifestyle factors that we'd be interested in to promote healthy aging, whether it's walking or nutrition. And he'd say, Doc, can you help me live to 100? You know, this is 35 years ago.
And I don't know that... So he was 65 roughly at the time. Exactly. Just retired and wondering if he can make it to 100. Oh, that's another thing. He's never retired. Never retired. Interesting. A lot of these people just keep working. Interesting. He goes into the office several times a week. Really? Yeah. So this is another interesting thing is that they're committed. They have a purpose.
They're very upbeat about what they're doing. And I'm usually one to look at hard data. And these are soft data points, like you were alluding to, Sande. So it's really interesting. So you have these two patients. They're both 98, 99 years old now.
But Mr. R.P. Ray had heart disease for 30 years. Yeah. So since roughly his late 60s. Got COVID at 96. Not terrible. We didn't wind up in the hospital. But he got COVID at 96. That's concerning. He must have a lot of resilience, would be my guess. Is resilience then a characteristic of super agers? Yeah, absolutely. I think that's tied into the immune system predominantly because these three diseases are
have a common thread. Not only are they, you know, 20 years plus in the making,
but they all are related to our immune system being either in disarray, immunosenescence as we age. Some of us have more of a problem with our immune system doing its thing of protecting us than others. And that immune system, I mean, a whole chapter in the book is about the remarkable ability we have today to turn it up or down. That's why we need a real immunosuppressant
which is in the works right now, to be able to say, you know, when you go for your checkup, how's your immune system? We keep coming up with more ways to amp up our immune response, whether it's personalized neoantigen vaccines or checkpoint inhibitors, all sorts of antibody conjugate drugs. And if we can detect people who are at high risk for cancer,
and then check their blood, their plasma for any tumor DNA so it's at the microscopic level, we can then get their immune system into high gear so they never have to have that cancer take hold, no less spread. So that's why I do think we're going to make major inroads for all three of these AIDS-related diseases.
So I think a lot of people understand the immune system when it comes to fighting off an infectious disease, a virus or bacteria. And perhaps even with cancer, you know, your immune system is constantly maybe targeting abnormal cells, mutated cells, and hopefully quashing those from the body. But what about with regard to cardiac disease and dementia? How does the immune system play a role there?
Yeah, well, what's fascinating, it's the inflammatory response in the brain that is what's causing the loss of brain tissue. And that is really what drives dementia, Alzheimer's, as well as Parkinson's, the second most common neurodegenerative disease. So we just keep learning that if we can block inflammation and the immune response in our arteries, in our brain,
Or on the other hand, bring it to a higher level of protection against cancer. These are the ways that we're going to be preventing the big three. Are we thinking the immune system as friend or foe here? Well, it's both. The amazing thing today is that the only way we can assess an immune system effectively
in a patient routinely is looking at the ratio of their white cells, neutrophils, to their lymphocytes. I mean, we know how important this is. It's the second most complex system in our body after the brain. And we haven't done anything about it. So now, you know, the data keeps pouring in. If we're going to get ahead of...
the age-related diseases, we've got to add in this missing component. You have to have the right level of immune system protection or protection from it at the right time and the right person. And we're going to get there. We don't have all the pieces together, but we have enough to make a difference even now. Dr. Topol is pointing out something pretty important here.
The immune system, like the brain or the gut, can malfunction. Sometimes it is too strong. It actually ends up attacking the body itself. Sometimes it's not strong enough and is unable to fight off viruses and disease. And sometimes it just gets dysregulated, sort of turns up inflammation, which is part of its job, but then doesn't turn the inflammation back down.
Dr. Topol says scientists are working on ways to measure how well the immune system is working by mapping out something known as the immunome, that is, all the genes and proteins of the immune system, and then assessing how well they are functioning. They're also working on therapies to treat and regulate the immune system when it does malfunction. Now, when we come back, Dr. Topol is going to explain why new disease screening techniques might help us all live longer.
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Welcome back to Chasing Life. I'm speaking with Dr. Eric Topol about his new book, Super Agers. Now, one of the big topics he raises is proteomics. That's the large-scale study of proteins in the body and how AI might be able to help researchers and doctors tell how fast a person's organs are aging, all of which then can help predict the onset of disease.
In the book, you write quite a bit about these proteomic organ clocks, which can estimate the pace of aging for your organs, your brain, your heart, your liver, kidneys, and your immune system. So these clocks can sort of tell you if your heart is aging faster than the rest of your body. Other molecular clocks could calculate your biological age versus your chronological age.
And then there's the epigenetic clocks that you write about as well, which read parts of your DNA, for example, that could be taken even from a saliva sample. If someone gets genetic testing, a lot of times you're sort of told, look, you may have a predisposition for something. Maybe it's Alzheimer's dementia, for example. Right, right.
It feels vague and sometimes unnecessarily alarming for people because they don't really know what to do with that information. But instead, you're saying with the addition of doing proteomics, looking at proteins, looking at the genes specifically, and also using large AI models, you can start to be much more predictive about things. Do I have that generally right?
Yeah, I mean, it turns out we can assess anywhere between 6,000 and 11,000 proteins in our plasma through a limited blood sample. And that one tube of blood, with AI, we can then say organ clocks, like your heart, your liver, brain, kidney. Are any of them out of whack in terms of aging compared to your chronologic real age?
And we have this marker, which is extraordinary, you know, P-tau-217, a single protein. And that protein predicts Alzheimer's more than 20 years. And it's as accurate as a cerebral spinal fluid from a lumbar puncture or a PET scan, a tau PET scan. It's incredible. The polygenic risk score by itself has been somewhat of a disappointment. That's all we had up until recent times.
You'd say, okay, you're at risk for Alzheimer's. But you didn't know if that was age 79, 59, 99. You didn't know anything. It was so vague. Now we have this, you know, advanced ability to take notice 20 years before. And then, of course, if you can...
reduce that, that ought to be accompanied by protection and at the very least significant delay and ideally full prevention. The prevention may take more help than just lifestyle. It may take some drugs that are in the pipeline. Many drugs are being developed to help in this. So we don't just rely on lifestyle factors. But that's another thing we know.
that lifestyle factors are tied into prevention of heart disease, 80 to 90 percent, and about half of cancer and neurodegenerative diseases. We don't get people to adopt these lifestyle changes and become fanatics about it. But when they find out about a particular risk in them, the chance would hopefully be much better.
That's a really interesting point, Eric. I think, you know, as a general rule, you know, adopting healthy lifestyle habits into your own life, that's always going to be the advice. But the idea that so many people don't do it, despite knowing what a healthy lifestyle is, once you have a marker, in this case, you're talking about a P tau 217, and you see it elevated, and then you see it potentially come down in response to lifestyle changes, that's wildly motivating, I think, for people. Yeah.
You know, absolutely. Kind of like a cholesterol test for heart disease. The fact that we have a test like that now, right? That we can, you know, when you really bring down your cholesterol, you really bring down your chance of developing heart disease, which is terrific. We haven't had that for the brain, right? So this is big stuff. And of course, only in recent years have we seen the remarkable refinement of
of these microscopic detection of cancer, the so-called multi-cancer early detection tests. The problem is, of course, a lot of testing we do today, like mass screening,
It's not being done because a person's at risk. We treat everybody the same, but we're so much smarter than that. You know, 88% of women will never develop breast cancer in their life. Why do we recommend all women have these frequent mammograms, which are accompanied by all sorts of false positives, even false negatives, and anxiety, and callbacks, and biopsies, and all sorts of unnecessary stuff?
We are much smarter than that now with respect to being able to find who is at risk,
you know, when, what, and how we can counter that risk and prevent diseases. So that's why I'm excited. It isn't about reversing aging. It's about a whole different approach to preventing age-related diseases. And possibly cutting down on too much testing, it sounds like. Yes. Let me ask you this, just on a personal note. My mom was diagnosed with breast cancer on a routine mammogram when she was in her late 50s. She's doing well still. She's in her early 80s now.
I have three daughters who are, you know, almost 20, 18 and 16. How do you think their lives would be different based on everything you're saying? I'm worried about them developing cancer, let's say, in their lives. Instead of getting, starting mammography at, what is it now, 40, 45? I can't remember what the guideline is. Yeah.
There's two different ones, but yeah, 40 or 45. And it went down. It was 50. It used to be 50. And I know there's always debate with regard to the Preventative Task Force in terms of what that age should be. But let's just dispense with all that and say, so should they get genetic testing, get proteomic testing, and develop their sort of risk score now?
Well, I mean, for one, your mother could have BRCA testing if she didn't have it, BRCA1 and 2, and polygenic testing because there's a bunch of other genes that are tied into risk. So it'd be nice to know about her genetic story, which can be obtained. I don't know if they did that. You know, a lot of physicians don't.
which they should because of the effect on the next generation. And we men can be carriers of BRCA1 and 2 as well, and other significant so-called pathogenic mutations. So that's one thing, but then your daughters are young and they're not really at the time where they would get into, unless there was something that turned out to be the case with your mother.
So at any rate, when they were a bit older then, your daughters could get the clocks. They could get their proteomic clocks, even epigenetic clocks to see how they're aging body-wide. So that's when they would hopefully, if they are at risk for cancer or heart disease or neurodegenerative, they'll know way ahead of time and be on a really great program so they don't get these diseases.
So, again, I just want to make sure we're defining this term clock really well. So in addition to genetic test, and by the way, my mom was negative for BRCA1 and BRCA2. Oh, good, good. So if you have this capacity to not only do genetic testing, but also to introduce the concept of a clock to it saying, okay, you're at risk. Now let's put a clock on that risk. Here's the timeline of that risk.
Which, by the way, I didn't realize you can get so granular as to say, hey, look, maybe in your early 70s is when you'd start to develop symptoms of Alzheimer's, for example. But with regard to breast cancer, if you can get that granular, what then? Does that mean maybe, let's say one of my kids had that and they had a clock attached to it, they would get more frequent mammograms? Or what would it mean for them?
Yeah. So remember, when you get this, there's two levels of the clock. One is body-wide aging.
You know, I kind of liken that to how are we rusting? How are we adapting to aging? And that's going to just say your real age is, you know, 65, but your body-wide aging is, you know, is 70. Now we say, okay, let's look at the organ clocks. We have all the vital organs to compare with your actual age. And they say, you know what, they all check out except this immune system.
and then say, "Hmm, we're going to be checking this on a more frequent basis." And not this primitive way we do it today, but a more advanced way. And that's when you say, "Hmm, the immune system down, this person has a high risk for cancer." That, of course, isn't the case with your daughters, at least from your mother's data.
But let's say somebody was at high risk. That's when you would do serial assessment of their plasma for tumor DNA, which is the earliest sign. And you don't want to wait for an MRI. You would go with a blood test.
that's much more sensitive than looking, or better than looking for, you know, Goomba on the MRI scans. So there's so many things that we have some control over to be a healthy ager now. Are you a super ager based on everything you've learned about yourself? I hope to be. If I can get another 10 or 15 years without an age-related disease,
You know, that'd be great. And I've really gone double down on the things that I can do to help get there. In terms of your lifestyle. Yeah. I mean, I wasn't doing strength training. I was a terrible sleeper. And now I'm tracking that every night with both a smartwatch and aura ring to try to get maximal deep sleep. I wasn't working on posture or balance and I wasn't careful about ultra processed food. Now I'm reading labels and I've developed a real aversion to things that are in plastic.
and then don't use the microwave to heat up something that's in plaster because that is the worst case scenario. But, you know, so many things that we can do. And what's exciting, you know, these are kind of dark times and
in biomedicine with gutting of the research budgets and public health and whatnot. But I'm incredibly optimistic about where we're headed right now in terms of our ability to, which we didn't have before, to prevent these big three diseases.
Your book, Super Agers, An Evidence-Based Approach to Longevity. And you've always been known for that, the evidence-based component of things. There's a lot of folks out there who are talking about aging, talking about longevity. They don't have the evidence behind this. And you really spend a lot of time reading, putting that evidence together, making it make sense for you, and then helping make sense for everyone else, which I really appreciate. Yeah.
Thank you. That means a lot coming from you, Sanjay. I mean, I think a lot of these people do have good intentions, but they kind of get ahead of themselves, you know, recommending things that, you know, never had any backup, you know, never had the proof points. And so, unfortunately, there's a lot of confused people out there. Everyone who's listening should read this book.
But also keep in mind that science evolves. We learn more and more. So hopefully you'll come back and continue to educate us. Thank you for joining us. And you're welcome back anytime if you can make the time. Thank you.
You know, I got to tell you, whenever I speak with Dr. Topol, I know I'm going to learn something, something about the future of medicine. I've been hearing about super-agers for a long time, people like Lenore and Mr. RP for years. But it is exciting to learn that with the right testing and technology, more people than ever may be able to live longer and healthier lives. So special thanks to Dr. Topol and also to Lenore for coming on the show and sharing her words of wisdom.
Chasing Life is a production of CNN Audio. Our podcast is produced by Aaron Mathewson, Jennifer Lai, Grace Walker, Lori Gallaretta, Jesse Remedios, Sophia Sanchez, and Kira Dering. Andrea Kane is our medical writer. Our senior producer is Dan Bloom. Amanda Seeley is our showrunner. Dan DeZula is our technical director. And the executive producer of CNN Audio is Steve Liktai.
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Special thanks to Ben Tinker and Nadia Kanang of CNN Health and Wendy Brown. This week on The Assignment with me, Adi Kornish. The rise of buy now, pay later services or BNPLs. The idea is this. Instead of using traditional credit or debit to pay for your new sweater or TV or even your DoorDash order, you can break it up. And sometimes those payments happen every few weeks, sometimes once a month.
And it's clear we're not sure how to feel about it. Is this a dangerous fad or a smarter, healthier form of credit? Listen to The Assignment with me, Audie Cornish, streaming now on your favorite podcast app.