Q&A: Dr. Eric Topol on "super aging" (Pt. 1)

Part 1: "the most extraordinary thing I've ever seen in medical intervention"

Eric Topol. credit: Scripps Research Translational Institute.

Eric Topol is a cardiologist and one of the top 10 most cited researchers in medicine. I sat down with him for an in-depth interview last month to discuss the biggest takeaways from his best-selling book, “Super Agers: An Evidence-based Approach to Longevity,” which quickly became a New York Times bestseller.

I’ve distilled our 70-minute conversation, which took place in Dr. Topol’s office at Scripps Research Translational Institute, which he founded, in La Jolla, Calif., into the Q&A below.

This is Part 1; I’ll publish the second and final part of the interview next week. Dr. Topol called our conversation “exhaustive” — a compliment, considering most media interviews he’s done have only skimmed the surface of his book’s scientific strategies for achieving a healthy and vigorous life free of physical, emotional and cognitive diseases — aka, aging with strength. There’s a lot to learn from Dr. Topol, below.

“Eighty percent to 90 percent of heart disease, and 50 percent of cancers and neurodegeneration, are preventable”

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

Paul von Zielbauer, AGING with STRENGTH: Dr. Topol, you’ve written a few bestsellers, but until now none specifically about aging. Why did you write “Super Agers”?

Eric Topol: Each of the books I had done previously were trying to look at, “What's the next big thing in medicine?” “Super Agers” is about forecasting for each person to prevent the Big Three diseases of our species: cancer, cardiovascular disease and neurodegeneration.

The book's intent was to lay out that, while there's all this stuff going on to reverse aging, and that may be great someday, it's going to have risks.

On the other hand, there's this great promise that no one is really working on, using the science of aging to understand each person's aging process. There's all these biomarkers. I did the book primarily to anticipate where aging [science] has yield and excitement.

The other big reason was my longstanding interest in health span, healthy aging and the "Wellderly" — the people in their late 80s who have never had a chronic illness.

And then finally…we have these companies that are selling longevity, we have anti-aging supplements that don't do anything, we have Bryan Johnson and all these quacks. So we need the real truth out there, the facts. And I said, “Well, I can try to project where we can go and get the story straight.”

It's been really terribly predatory out there.

AGING with STRENGTH: You are appropriately aggressive at calling out the longevity charlatans and chiselers out there — Andrew Huberman, David Sinclair, Peter Diamandis, you mentioned Bryan Johnson.

Eric Topol: Peter Attia is on that list, too.

Paul: David Sinclair, a notorious longevity chiseler, has claimed that aging is a disease that can be reversed. Do you believe that aging is a disease?

Eric Topol: That's a really great question. Aging is a normal process, so it's hard to call it a disease. (We used to say obesity wasn't a disease, and now that we have a treatment for it, we say it's a disease.)

The question is, Is it the root of the three major diseases? Are most of the cancers and the cardiovascular and neurodegenerative diseases an outgrowth of aging? They're dependent on the aging process. So I don't think aging itself is a disease, but because of the way it affects our immune system — the buzzword on that is immunosenescence — and the way it increases our propensity for inflammation, "inflammaging" — those two interrelated processes of aging — [aging] basically invites diseases. It sets up for disease. So per se, no, but indirectly, yes.

AGING with STRENGTH: You get to that at the end of your book, where you say immune function is one of the mainstays of remaining healthy deep into old age.

Eric Topol: We did that study, the "Wellderly" study, of 1,400 people age 80 years and older who had never been sick. No medications. Yet their families mostly did not have that pattern. Lea Rosenberry was 98. Her parents died in their 50s and 60s. Her brothers died in their 60s, and yet she's 98 and perfectly healthy. That was the pattern we saw in the “Wellderly” study.

“It's striking how fast the inflammation in your body and your brain comes down”

So what is the explanation for that, if it's not in their DNA? My bet is it was these people's immune system, which is unlike most of us as we get older, where we lose our fine tuning, the integrity [of our immune function], so it’s more vulnerable and it allows cancer cells to get going and spread, or it's untoward inflammation in our brain, in our body, in our arteries that sets up the other two diseases.

So it's the immune system. I keep saying to myself that old thing about the economy: “It's the immune system, stupid!” Because it really is. And only now are we seeing the beginnings of our ability to assay comprehensively a person's immune system.

We should be having immune system testing as we get older, because it is the reason why aging can hurt us.

We don't have a test for it in the clinic. We have a stupid test, which is in your complete blood count, the ratio of your white blood cell neutrophils to your lymphocytes. It's basically worthless. That's the only thing we have today that tells us anything about a person's immune system.

We have this emerging thing called organ clocks, which I'm very excited about. There's also an immune system clock. But that's just [measuring] proteins and it may not be a very accurate window to the cellular component — the antibodies and the interferons.

The immune system is so complex and it [represents] the big hole in the story of extending health span. We have to be able to test people starting at age 50, 60, 70, especially the older they get. Because we have ways to control it. We can dial it up and down. We just don't know who needs to control what.

AGING with STRENGTH: Along with creating a robust immune system later in life, how should people over 50 think about keeping their organs young? And which ones should they focus on?

Eric Topol: First, you’ve got to find out where the vulnerability is, which organ, and then you can get all over it. Let's say it is the immune system, and you have a family history of cancer but you don't know what type of cancer. You do a polygenic risk score.

We have that for every common cancer.

Everyone should have a polygenic risk score for the major cancers. I mean, it's inexcusable, for example, that we have an American president [Joe Biden] who goes all these years, and then all of a sudden has Gleason 8 prostate cancer, which almost invariably would have shown up [on a polygenic risk score test] that he was at high risk — and it was never done.

We do screenings based on age. It may not be just age. It may be, “What do you know about your family?” You get some genetic assessment, whether it's whole genome sequencing or polygenic risk score, then you start to look at the protein layer and particular biomarkers. And if you do have a high risk for cancer, and your immune system is down, but there's no evidence of cancer from, say, a multi-cancer early detection test, a blood test, then you could just keep an eye on this immune system and rev it up.

We just saw how if you just give shingles vaccine to people, it reduces the incidence of dementia and Alzheimer's by 20, 25 percent. If that was a medicine, that would be huge. It basically just revved up the immune system so that their ability to deal with the amyloid and tau proteins and these misfolded proteins in their brain. It just gave them a better defense.

AGING with STRENGTH: Your book documents the big pillars of maximizing health span: Exercise, muscular strength maintenance, sleep, balance, nutrition, community and environmental factors, which the book calls “Lifestyle +.” How else should people think about maximum longevity?

Eric Topol: When you talk about nutrition, you’ve got to [consider] alcohol and salt and sugar. And then social interaction and being in nature. I was surprised at the body of evidence on these things. I didn't expect it. The environment, being in nature. And then along with that are the adverse things in our environment to try to minimize, whether that's [poor] air quality in your home or workplace or it’s plastics. And within nutrition, [limiting] ultra-processed foods and the forever chemicals.

The ultra-processed food story is pretty striking. And then these new categories, like you're bringing up, the social engagement, the beauty of the impact of being out in nature, for mental health.

AGING with STRENGTH: Longevity science can quickly get esoteric and technical, discussing ApoB, metformin, rapamycin, GLP-1s, polygenic risk scores, genomic sequencing, DEXA scans, SGLT-2 inhibitors. How should non-scientists figure out what they need to understand in order to maximize health span?

Eric Topol: On the one hand, it would be great if everybody adopted all the things we know about “Lifestyle +.” If everyone endeavored to do all that, we'd be way ahead in prevention. As outlined in the book, 80 percent to 90 percent of heart disease is preventable; 50 percent or so of cancers and neurodegeneration are preventable with what we know today. But most people don't do all these [preventative] things. So one of the [book’s] missions was, “Let's go with everything that's out there that we know to prevent.”

“Now we can say at 87, plus or minus two years, you will have mild cognitive impairment. And then another few years before you develop full-blown Alzheimer's. None of this could happen without AI.”

The problem is when you tell people to do all these things, most people don't do them.

So you don't just tell them, because it doesn't work. I mean, you try. As a doctor-patient relationship, I try. And some people will make a lot of big changes. But what I've learned, and what studies bear out, is that you can particularize the plan for a patient's risk — for example, heart disease — and that's what you go after. And that’s why you check these extra lipid tests like LP(a) and ApoB. And get you off red meat as much as possible and get you on an anti-inflammatory diet. For that person, you have a plan that uses a lot of that lifestyle [factors] but it’s much more directed.

Each person has a different strategy. For the people with cardiovascular, we're going to get the LDL down, whatever it takes, to very low levels. We're going to get LP(a) down. We're going for broke to prevent that disease.

For cancer, we're going to go into this early detection. We're going to get it at the microscopic level. We're going to keep your immune system high integrity so you don't even get microscopic cancer, because we've learned it's all about the immune system, why people get metastatic cancer.

And then for Alzheimer's, [there is] a biomarker called p-tau217. We've got the polygenic risk score for Alzheimer's. We've got the ApoE4 allele. So, for you, today, I could say, you have a high risk or don't have a high risk, and I can say when. I never could say that before. Before, I could say only, "We're going to do a polygenic risk score, and it says you are high risk for Alzheimer's. But we don't know if that's when you're 102 or when you're 62.”

Now we can say it's at 87, plus or minus two years, when you will have mild cognitive impairment. And then another few years before you develop full-blown Alzheimer's. So we are so much better positioned now with AI. And none of this could happen without the AI.

Because you're taking all these data points, billions for each person — everything in the electronic [health] record, unstructured text, all their lab values, where we say, “Oh, it’s normal, no issues,” but the AI sees the trend among normal lab values. AI sees in the image things that humans will never see. And you have all this assembled and then you say, “This is what we're going to work on for this person.” We have this lifestyle plan and, oh, by the way, the GLP-1 drugs, like Ozempic? That could be a big winner for preventing Alzheimer's.

AGING with STRENGTH: GLP-1s — glucagon-like peptides — seem to be an emergent class of wonder drugs. Ozempic is the one that gets most of the attention in the longevity conversation, but what should my readers understand about how GLP-1s may impact their health spans?

Eric Topol: Glucagon-like peptide is one of the gut hormones that we're mimicking with injectable peptides. GLP-1 is just one of the three hormones that are now into therapeutics, or at least a third receptor is. There's glucagon and there's GIP, which is the gastric inhibitory peptide, and then there's 15 more. The dual receptor, which is tirzepatide, has been shown to be much more powerful than Ozempic for weight loss.

“The gut hormone story is the most extraordinary thing I've ever seen in medical intervention”

But then there's another 15 more peptides that people don't even know about that are coming. But with just GLP-1, that one peptide, if you're obese, you lose weight but before you lose one pound, the inflammation in your body and your brain comes down. I mean, it's striking.

Now we know that the principal action of these drugs, or a big driver, is markedly reduced inflammation.

Some of these newer peptides that are going to be the next-gen, they are incredibly well at penetrating the brain, [via] the vagus nerve. So they'll have even more anti-inflammatory effect in the brain than we've seen with Ozempic.

So this is very exciting. When I say this is a miracle drug class, I'm not just talking about that first one, GLP-1, which took 20 years to figure it out, but about…