- Now, often we're warned about the risks of an aging population, the so-called demographic gray zone, the drain on the economy, medical services, and so much more.

But author and Dr. Eric Topol suggests that's no longer the case.

He argues that, in fact, new technology and medicine will provide us with vibrant, healthy lives much later on.

He joins Walter Isaacson to discuss what he calls a breakthrough moment in the history of human healthcare.

Thank you.

And Dr. Eric Topol, welcome back to the show.

- Great to be with you again, Walter.

- You know, this book, "Super Agers," it's a lot different than the books about how to age well and stuff because it's so evidence-based.

Were you showing this sort of as a counterpart to all these bestsellers that have all sorts of new theories but aren't evidence-based?

- That certainly was part of it.

I think, you know, the idea that we'd already been active trying to hunt down the source of healthy aging, of super-agers, of welderly, whatever you want to call these remarkable folks, was very different than what's out there.

And so, you know, trying to set the record straight, putting in some around 1,800 citations, but really, as you said, Walter, going over the real exciting advances in the science, too.

- We always talk about lifespan.

We want to increase lifespan.

And you talk about healthspan.

Why do you focus that way?

- Yeah, I don't see the reason to promote longevity if you're not also getting as much healthspan out of it as possible.

Because if you have someone of advanced age and they're so frail or demented or something that's really compromised terribly their quality of life, that isn't what we're aspiring to do.

The real goal is just to get as many fully healthy years as possible.

And we're not doing that now.

Most of the American population are the elderly, not the welderly or the super-agers.

But I think we have the capacity now to flip this.

And over the years ahead, we'd have a lot more welderly and super-agers than people with chronic age-related diseases.

- You both begin the book and you end the book with a couple of patients.

I think it's Mrs. L.R.

and Mr. R.P.

Tell me why you use them.

- Yeah, so Lee Rusall, who's happy to be identified, but was referred in the book, as you said, Walter, to Mrs.

L.R., she was a patient recently in my clinic, 98, and incredibly intact.

And also with a great sense of humor and just having a very rich life.

And she made me think about our welderly study of the 1,400 people like her, the average age was in their late 80s, never been sick, no medications.

These are a rarefied group of people.

It took us seven years, Walter, to find 1,400 of these folks.

Well, because she's so emblematic of healthy aging and the striking features were her relatives, her parents and her two brothers died 30 or 40 years of age younger than her.

She's the last one standing.

- So it wasn't just purely genetic?

- Not at all.

And in fact, that's what we found in our welderly study is that when we, not only was the familial pattern a lot like Lee Rusall, but we did whole genome sequencing, and we found very little that could account for this remarkable super aging status.

- So let's start looking at the factors for super ages and start with lifestyle, if you would, what you call lifestyle plus.

- Yeah, because while we've concentrated largely on diet and exercise, sleep is equally important.

And then there's these other factors like social engagement, avoiding isolation, being out in nature.

These have really strong support, as do the environmental toxins of air pollution, of forever chemicals and the microplastics, nanoplastics story.

So it all fits into a simple model that the things that promote inflammation, like a poor diet, ultra processed food, overdose of proteins, lack of deep sleep, the lack of exercise and physical activity, the toxins from our environment.

They all fit in the model that if you promote inflammation that occurs more as we age or immunosynthesis, the deterioration of our immune system as we age, which are intertwined, that's where you get age related diseases.

- You talk about sleep though.

Can we go back to that?

Because one of the surprising things in your book was you said you should get about seven to eight hours of sleep.

If you get less, it's a problem.

But you also said if you get more, it's a problem.

- That's right.

And the question is, even start to see over seven hours, do you see this adverse linkage?

The question there is, is it because people have depression or is it really something about too much sleep that is not helpful?

We don't really know, but the population studies where of course, everyone's different.

And we emphasize that if you look at it from a big population level, seven hours, not often what's referred to as eight plus is the optimal level.

But obviously that'll vary from one individual to another.

- What does sleep do for us?

- Yeah.

That's the big thing that we've learned in recent years.

So the one component of sleep known as deep sleep, the slow wave of sleep typically occurs in the early hours of sleep.

That is the critical time when we use our glymphatics, not lymphatics, but glymphatics in our brain.

These are the channels that get the waste products, these toxins that we accumulate through our brain metabolism each day.

And at night or whenever you sleep, that's when these glymphatics go to work and get these toxins out of our brain, which are very pro-inflammatory.

If you don't get enough deep sleep, which as we get older, we lose our propensity for deep sleep.

If you don't get enough, you don't get these waste products out.

And not only that, but if you take medications like Ambien, everything points to that you get basically a backup of these toxins.

You may get some more sleep, but you're not doing anything regarding deep sleep and clearance of these waste products.

- With alcohol, every year we seem to have some new studies saying one drink is horrible, one drink is great or whatever.

There's a new study out from the American Heart Association.

I saw that you even have written about some.

Tell me what you feel now about alcohol consumption.

- Yeah, the point you're making, Walter, it's really the problem.

Depending on which report, looking often at the same data, the conclusions are quite different.

Overall, it does look like if you are at risk for cancer, particularly certain types of cancer like colon or esophageal and even breast cancer, if you're more than one to two drinks a day, you're getting into a risk zone.

There is a convergence of that.

There's also the National Academies of Medicine and the Circulation American Heart reports that say, "Hey, there really is some benefit of alcohol for men up to one drink per day or seven per week and for women, perhaps four or five per week."

So we have mixed data.

The problem, again, is we're trying to come up with these reports and recommendations for all people.

- By the way, let me push back on the all people.

Why can't I sequence my genome, put it in a computer and have it tell me, "You're okay with salt.

Your cholesterol is not going to be affected by meat or it will be.

And by the way, you can do alcohol or you can't do alcohol."

- We should be doing that because we can do that right now, Walter.

Like for example, you can get a polygenic risk score, which isn't even require a full genome sequence.

It will tell you every different cancer risk.

If your cancer risk is really low across the board, your concern about drinking alcohol would be less, not to go excessive.

But we don't do that.

We treat everybody the same and this is really part of the problem.

And that is the ticket to prevention as well.

- Wait, well, why don't we do that?

- Yeah, it's because the medical community is slow, slow, slow, so slow to adopt the body of knowledge.

Everything sits in this research compartment, like a different orbit, Earth one, and the medical practices like Earth two.

And it's just really frustrating.

It takes so long to take validated, compelling data and put it into daily medical practice.

- One of the biggest differences between having a long lifespan and a healthy long lifespan or a health span is dementia and specifically Alzheimer's.

What causes Alzheimer's?

- Well, there's been the amyloid hypothesis and the tau hypothesis.

Basically the story is there's misfolded proteins that get in the brain, develop in the brain, and we develop a very severe inflammation response.

If we do that, we're gonna more likely go on to Alzheimer's disease.

Now, turns out a lot of healthy people may have these misfolded proteins, but they don't have the inflammatory response to them.

So you don't have to worry about the amyloid hypothesis or the tau hypothesis.

Basically, what you want is to not have this misfolded protein and its inflammatory reaction occur in your brain.

We have a way to do that now.

We have a marker called P-tau-217 that a lot of people and doctors don't know about.

And it can tell us more than 20 years in advance that you are a high vulnerability.

- So what happens if I learn 20 years in advance?

- Yeah, that's what's great.

It's kind of like if you've been following, I suspect you have, because you follow a lot of stuff, the LDL and the cholesterol story.

You lower the LDL and you have less heart disease.

The same thing, if you have a high P-tau-217, and the only reason to get it is because you have a familial pattern of Alzheimer's, you have an APOE4 or a polygenic risk that's increased.

Anyway, you're at higher risk, you get the P-tau-217.

And if you're relatively young, you're in the 40s or 50s, you've got a 20 year lead time.

Now, when you start to lose weight, exercise, have a better diet, that's not pro-inflammatory, sleep better with high quality deep sleep, those markers come down.

It's remarkable.

It's modifiable.

And so we should be able to prevent Alzheimer's because we have brain clocks, we have these markers, we have even healthspan clocks from these proteins in our blood now.

So you can not just use these clocks to tell about risk and markers, but then you can use them to see if the interventions are working.

And one of the exciting things, I know you're aware of this, but these GLP-1 drugs like Ozempic and Mungero, Zep-Bound, they are being tested for Alzheimer's in people who are not overweight in large trials, which we'll have in the beginning of next year.

That may work because these agents, these drugs markedly reduce inflammation in the brain and in the body.

And we haven't had any drugs like that previously.

So if we can control the inflammation process and these drugs, as well as other gut hormones are going to do that for us, we're going to have a way, not just lifestyle factors, but in the high-risk people to bring down the markers, the metrics of the aging brain, the sick brain that's emerging towards Alzheimer's years before people ever get mild cognitive impairment.

- Wow.

You talk about Ozempic and the similar GLPs.

How much of a miracle drug is that?

- Well, we've never had a family of drugs like this.

And I want to just submit to you that we're still in the early phase of this.

What we've learned, now there's like 15 different gut hormones.

We only are into two or three of these that talk to the brain and talk to the immune system.

This gut-brain axis is one of the most important discoveries for our health in history.

And this drug class reflects that.

As you know, these GLP-1 drugs are not just influencing diabetes, you know, favorable effects, improving people's obesity status, but they're also improving the heart, the kidney, the liver, I mean, virtually every organ.

And the last one to be tested of major organs, which is in progress in large trials now is the brain.

But even if these, even if Ozempic, which is the lead one as far as these trials, even if that doesn't hit, there's many other of these gut hormones that are going to be in pill form, various combinations, some of which get in the brain far better.

They don't rely just on the gut to brain signaling.

That's what's going to take us to ability and these other anti-inflammatories to prevent these three diseases, cancer, neurodegenerative, and cardiovascular, because they all have common threads and they all take 20 years to take hold in our body.

- The things you've talked about, the immunotherapies, the GLP and the Ozempics, all were part of basic science research that led to discoveries that may not have even been expected.

And we move it from the lab bench to the bedside, but now we're cutting basic science funding and the National Institutes of Health.

How harmful is that going to be to the breakthroughs we're just beginning to see?

- Well, you've nailed it there because this is the most extraordinary time in my four decades in medicine where these discoveries, and of course, the multimodal AI to analyze all the person data is here and now.

So we are at the extraordinary moment of a series of breakthroughs, some of which we've reviewed in our conversation.

And at the same time, we're taking down the chance for building on this by seeing near $20 billion gutted out of the NIH.

And then all the other public health and science agencies of our government are similarly being dismantled.

So our ability to follow through and build on this progress is going to be profoundly compromised.

It will go forward, but at a different pace.

- Wait, wait, let me put a fine point on it.

You're saying these cuts will cause more people to die of cancer?

- Well, to put it another way, the advances that we could make in cancer to save lives and prevent cancer will be put many years forward.

So the corollary of what you just said, I believe is true.

We're missing the chance to have better treatments and preventions by not supporting our biomedical research engine, the crown jewel of the world, by just taking in a reckless way, taking away its support.

It's no doubt going to hurt the health of a large number of people in the United States.

- Tell me about health inequities in the United States and whether that's a problem for overall health.

- It's a big issue.

And it's one of the biggest concerns is the things that we've been talking about, the prevention of age-related disease.

The people who are the most indigent, the lowest socioeconomic status have the most to gain, the most need, and they may be the least to be able to be advantaged here.

So you have to go after this.

You can't just assume when you have some new thing that the people who need it the most are going to get it.

And we could make inequities worse.

And they're already at a serious level in this country.

So it's certainly one of the concerns that I have.

- Dr. Eric Tobel, thank you so much for joining us.

- Thanks, Walter.

I really enjoyed the conversation with you.