Q&A: Dr. Eric Topol on "super aging" (Pt 2)

Part 2: "The way to a person's brain and to healthy aging will be through their gut."

Dr. Eric Topol. Image courtesy of Aspen Ideas Festival.

Below is Part 2 of my wide-ranging interview of Eric Topol, a cardiologist and one of the top 10 most cited researchers in medicine, about the biggest takeaways from his best-selling new book, “Super Agers: An Evidence-based Approach to Longevity.”

Read Part 1 of our Q&A session, which took place in Dr. Topol’s office at Scripps Research Translational Institute, which he founded, in La Jolla, Calif.

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Reporter’s request: This interview has no paywall but required several hours to research, conduct, transcribe, edit and format. If you find what you read here helpful, please consider making a small, fair contribution to support it.

(This interview has been lightly edited for clarity and length.)

Paul von Zielbauer, AGING with STRENGTH: Your book is a not-so-silent indictment of the American healthcare system, or “sick-care” system, as you’ve called it, which isn’t set up for prevention. Should people be setting aside money, just like they would for a vacation every year, to spend on their own health span?

Eric Topol: This is a really important question you're asking, because firstly, we didn't really have the ways to prevent these big three diseases (cancer, cardiovascular disease and neurodegeneration) before. It's only now. We needed AI for the analytics, and we needed the layers of data, and many of those layers have only recently become available or will soon be available.

We are not in a good position, in this country, to do this. You touched on it because we have a private-insurance based [system], where insurers don't have a long-term interest. They just want to get you or your employer to sign up for another year. Why would they want to prevent the diseases that cost money to prevent? Other countries will do this first because they're looking out for the countrywide health.

In the United States, we have such a perverse incentive system, which is not set up for prevention. To turn that around is going to be hard.

Putting in a prevention savings account, that's not really the problem. The problem is, how do you get these assessments? When are we going to have immune system testing for low cost? And how are we going to get it so it's not just for the affluent but for everyone, because it's an incredibly smart investment?

It costs huge amounts to treat a person with Alzheimer's or cancer or even cardiovascular disease. Are we ready to invest in prevention and make it across the board, whether it's Medicare, private insurance, whatever? I don't know that our country has the boldness to take on that initiative.

It isn't a prevention system, and it isn't easy to morph it into a prevention system. Just because of the way it's structured.

“When are we going to have immune system testing for everyone, so it's not just for the affluent but for everyone?”

AGING with STRENGTH: Should people be willing, then, to invest in their own healthcare, even if that means setting aside thousands of dollars every year for tests that insurance won’t cover?

Eric Topol: I'm into that democratization and more self-advocacy for people. The problem is all these companies that are marketing longevity. There's Peter Attia's Biograph, and Function [which Andrew Huberman¹ advises], and all the rest. They'll give you all these tests for a big price. That isn't good, because you're doing tests indiscriminately and you're going to find things that you don't know what to do with — they are rabbit holes.

They're advocating total body MRIs with no data to support it, except for Kim Kardashian's endorsement. So the question is, how do I get the right test for me instead of getting hundreds of tests that I pay big bucks for and I'm going to get these crazy results that are spurious?

It seems rapacious. I’ve advised some of these companies. I ask them why they don't just do the tests that are based on a person's risk. The accuracy is much higher. The idea they have of getting more tests isn’t a good idea [because] It's just getting the wrong tests for the wrong people, and too many tests.

But standard medicine is leaving too many unsolved questions about a person's risk. For example, the medical community has been against polygenic risk scores, which keep getting better every month, every quarter. We can pick up people who don't have any family history of heart disease and very accurately say, “You're at really high risk for heart disease.” And then we can get all over them, prevention-wise.

So why aren't we using polygenic risk scores, which you can get for less than $50? That would be one kind of starting point, because people don't understand that even if [a disease] is not in their families, the unique combination of variants [formed by combining] your mother’s and father's DNA can give you a disease burden that you didn't know about.

And that's how you find it: through a polygenic risk score. Or, for $200, your whole genome sequence, if you're worried about cancer in your family. But we're well past just genomes. Now we're into biomarker proteins.

AGING with STRENGTH: Who isn’t worried about cancer? Especially given what you said about how our DNA isn’t simply the sum of our mother’s and father’s?

Eric Topol: What I would say is, get a polygenic risk score for the cancer conditions, heart disease and Alzheimer's first.

If you have a high polygenic risk score for one of the cancers, let's say colon cancer, then I would get a whole genome sequence to see whether there are certain variants/mutations that add more to that risk. So you start off with a cheap test, 50 bucks, then you get a polygenic risk score. I put in the book a bunch of reputable companies that can do them. Then you go to the genome sequence, for $200.

Let's say you're at high risk for Alzheimer's. Well, then you get a P-tau 217, you go to Quest Diagnostics, or LabCorp, it costs $190. And then you say, “Okay, my p-tau217 is up. It goes along with all these other things because I have a family history of Alzheimer's, I got an APOE4 allele. But now I have a test that I can use for my exercise and my lifestyle and all these things to bring it down. And hopefully, in the future, GLP-1 or one of the gut hormone remedies or many other drugs that are in the hopper for preventing Alzheimer's.

AGING with STRENGTH: I hear you saying that people do need to sort of be their own Sherlock Holmes here.

Eric Topol: Yes.

AGING with STRENGTH: Don’t start with the tests that are $500, for no good reason, but rather with the affordable tests and then follow that breadcrumb trail. Is that what you're saying?

Eric Topol: Yeah. That's a good way to put it. But don't go and get a total body MRI. Don't do that.

AGING with STRENGTH: What about a DEXA scan, which you can get for $50 or $75?

Eric Topol: That won't tell you about your risk for diseases. That will tell you, if you're on a strength training or weight loss program, [what your percentage of muscle and body fat is]. That's the solution to BMI.

By the way, I should have put in the book, but if you go for a DEXA scan at most hospital systems like mine, all you get is your bone density. You get nothing about your fat and your muscle. So you have to go to one of these strip-mall companies, like I had to, to get the real DEXA scan. I paid $70. I think they even have, you know, holiday sales or whatever.

Now I want to do it again, because I did that just at the beginning of my kind of strength training campaign. I'm the strongest I've ever been in my life. I want to see how much muscle I’ve built. So it's like you say: Aging with strength. And it's an amazing difference.

AGING with STRENGTH: Can I ask you quickly about BMI? Obesity rates in the United States have gone through the roof — 40% of American adults are now considered obese. But obesity is based on BMI, which, as you mentioned, is a bad test because it doesn't distinguish between fat and muscle. So isn't that 40% rate false also?

Eric Topol: Yeah, it's off.

AGING with STRENGTH: So is there less of an American obesity problem?

Eric Topol: Well, we don't know. It could be more. It's probably less because you've got these athletic people that have big muscle mass and their BMIs are 30.

AGING with STRENGTH: I want to get to something you and your book say is extremely important to understand: the brain-gut axis. What is it and why is it important?

Eric Topol: Only in recent years have we gotten fully in touch with the many ways that the gut talks to the brain and vice-versa. Parkinson's disease has long been thought to emanate from the gut, not the brain, and there's more and more data to substantiate that. But that's just one aspect.

There's direct nervous system connections like the vagus nerve that goes from the gut sensory neurons right through the brain stem. The gut hormones actually talk to the brain directly.

What is amazing is how gut hormones talking to the brain modulate inflammation and change the reward circuits in the brain. So people don't just lose weight, they markedly curtail alcohol, cigarettes, gambling — anything they're addicted to. Their reward circuits get rewired. They eat healthy food. They not only eat less food, they don't want to eat the junk they were eating.

Peter Attia’s book was pretty good, with a few caveats that I worried about, but then he's gone off and done this”

Now we know there's this dramatic shift in the inflammation and the immune system from the gut hormones. There's a whole chapter on the immune system in the book. We learned how the brain is mission control for the immune system. We've also learned that the two [organ aging] clocks — the brain clock and the immune system clock — those are the two clocks to pay attention to, because that is healthy survival², right there.

If I only could have two [organ aging] clocks, those are the two I want. And, by the way, those will be available in the next year.

AGING with STRENGTH: Organ aging clocks for the brain and the immune system?

Eric Topol: Well, for all eight [organ aging clocks], but brian and immune are my top two. I just met with the guy from the company [doing this], and he wants to get it out for $100. They test up to 11,000 proteins, and then the AI partitions out which proteins matter for each organ. I mean, it's the real deal. I'm glad it's going to be inexpensive. It's going to be routine someday. It's our first gateway window into our immune system and it's an invaluable marker of our brain's pace of aging.

These are tests for the gut-brain axis. Now, what is interesting is they've started trials, and are almost done with Ozempic, to prevent Alzheimer's in lean people, not obese people. It would have been even better if they did trials with people who had accelerated brain [aging] clocks.

This gut hormone connection [to the brain] is one of the biggest shifts in our understanding of the biology of humans. These are center stage now. It's not just the science part of aging, it's that we can manipulate them, we can mimic them, we can block them, you know. The point being, the way to a person's brain and to healthy aging, will likely be through their gut.

AGING with STRENGTH: That's the money quote!

Eric Topol: Yeah. Who would have guessed? The immune system is so entangled, so intertwined with what's going on in the gut. I mean, would I have ever thought that was possible? Never.

AGING with STRENGTH: On page 225 of the book, you write that "someday there will be a place for heritable human genome editing." How do you think about human genome editing and the ethics around designer babies?

Eric Topol: I'm not keen on embryo editing, especially with the misdeeds we've seen. But I do think eventually we'll get there. It starts to become the changing of humans. I'm much more excited about taking the somatic genes we have and doing that for preventing these three diseases. So, for example, if I'm an APOE4 carrier, can I have my APOE4 turned into APOE2?

That'd be great because my chance of Alzheimer's would go way down. And as I mentioned in the book, there's already work being done to do that in people.

And then what about risk of heart disease? If I could just get a shot, a PCSK9, it works in the rare disease of familial hypercholesterolemia and I never have to take a drug the rest of my life because it prevents heart disease. I’d say, "I'll take that."

So I'm much more keen on the common diseases that will be approached by genome editing than I am about the embryos, because it's much more dicey.

AGING with STRENGTH: I'm barely keeping up with you on this stuff. Average folks who wants to be healthy, who are 50 and have a busy life — where can they go to learn more about all the acronyms?

Eric Topol: I think the new AI searches are great. So you could go to Perplexity. You could go to Gemini and Claude. Not only has that really gotten so good now but it also will be very current. A lot of these things are constantly evolving. So that's how I get good information.

AGING with STRENGTH: Can I ask you about intermittent fasting and/or calorie restriction? I know these are different things. Is either a longevity helper?

Eric Topol: There's no data to support it, including the guy at USC.

AGING with STRENGTH: Valter Longo?

Eric Topol: Yeah, but it’s data on mice and yeast, not people. That's the problem with all these. They look really good in rodents, but we don't have the data for people. He may be right, but we don't have any good convincing, even remotely compelling data. Now, is it good for weight loss? Yeah. It works well for weight loss. And if you keep your weight off and you avoid obesity, that should be good. Most people can't do that. A lot of people swear by it.

But the smart thing would be to eat your evening meal and don't eat anything else until the morning. They might help to extend health span, but we have no evidence.

AGING with STRENGTH: I’ve seen doctors advocate for the fast-mimicking diet, saying that science clearly shows that after a 72-hour fast the body starts cleaning out the zombie cells. Is that b.s.?

Eric Topol: It's just not adequate evidence to make a call on. I always worry when you publish some work, and then you have a company selling based on that publication.

That's what Peter Attia has done with his Biograph company. His book was pretty good, with a few caveats that I worried about. I had talked to him about that, but then he's gone off and done this. The guys at USC? Just do the science, okay? Don't make a company out of it, or go ahead and make a company, but not dependent on the science papers.

AGING with STRENGTH: You’re saying separate your research interests from your financial interests; otherwise, you lose your credibility?

Eric Topol: Because then you say, well, that paper that you had in Science [magazine] where it really wasn't compelling, it was suggestive, and now you formed a company and you're selling it. They don't have the sine qua non, the nuts of the evidence. And now they're going to sell it. If you're going to start a company, do it on something that has evidence.

“This is a much more exhaustive interview than I expected. You are way ahead of the curve.”

AGING with STRENGTH: I’d like to ask you about alcohol. There's been a lot of things written in the last several months about alcohol being entirely bad for you, regardless of amount. And then, more recently, I wrote about an NYU researcher who attempted to quantify how much drinking actually takes off your lifespan. She said the data is a bit murky, but that number might be 1.8 years per alcoholic drink per week.

Eric Topol: That's interesting. Here's the big problem: With alcohol, we're trying to treat all humans the same. That's really dumb. Because if it has a risk for a cancer — for example, all three [recent government] reports did agree that there's a breast cancer risk when you pass a certain threshold. But 88% of women never get breast cancer. Only 12% of women ever get breast cancer in their life. So those are the people that need to be in the alcohol worry category.

No recommendation can be prescribed for all human beings. We keep coming up with these cockamamie assertions — "alcohol causes eight different types of cancer." Well, guess what? It doesn't just cause the cancer by itself. You have to have a genetic predisposition to those cancers. If I give the same amount of alcohol to 100 people — big-time alcohol — only one might develop esophageal cancer. And guess what? That person had a genetic predisposition.

AGING with STRENGTH: I don't think people understand that.

Eric Topol: But that's the thing: people should know if they're at risk for something, and these recommendations should be much more specific than, “Here are the Ten Commandments for the human species.” That just doesn't work anymore. We're smarter than that.

AGING with STRENGTH: What keeps you up at night?

Eric Topol: What keeps me up is, we're chasing our tails, we're taking away all the funds from doing the research that we need. I mean, currently right now with this administration, we're gutting resources. We're throwing people out who we need, whether it's at NIH, FDA, CDC, HHS — the whole works.

We're not taking on the environmental toxicities that we have to take on, which this administration, at least RFK Jr., has acknowledged is important — ultra-processed foods, plastics, forever chemicals, air pollution, we're doing nothing. In fact, the climate crisis is intertwined with all these, and we're not addressing that. We're denying it.

We're not looking after our less-privileged people, underrepresented people who should have access to all these things, and they're the ones who need it the most, and they're the ones who have the worst air pollution, the most microplastics, the most ultra-processed food, et cetera.

We have this monumental, phenomenal opportunity to prevent the three biggest diseases of humans that curtail our health span, and then at the same time, the things that are holding us back we're in denialism or we're ignoring.

We can't get the big jump in progress without putting the priority and the resources on the things that are holding us back. Our exposure to these toxins and these things in our foods that Big Food has never been taken on. They just keep getting away with it.

The people that need this stuff the most, all these longevity companies don't give a hoot about them.

I care about these people. I want a solution that's inexpensive, that AI... AI is not expensive. It's software, basically. You know, I want this free intelligence for medicine, for health.

AGING with STRENGTH: Anything that I should’ve asked you about but didn’t?

Eric Topol: I think you got it covered. It's been an extensive discussion.

It's a much more exhaustive interview than I expected. What's great is you've been thinking about it a lot. So that's why you are way ahead of the curve.

1. Huberman is among the most aggressive of those whom I’ve branded longevity chiselers.

2. Here, he’s referring to newer research showing that human organs age at different, individual, rates, and the ability to keep two specific organs “young” — the brain and the immune system — appears to have the greatest association with healthy longevity, among all the body’s organs.