The Science of Super Agers

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We're here with Eric Topol,

he's the executive vice president of Scripps Research,

also a practicing cardiologist

and one of the most highly-cited scientists in medicine

and, you know, and yeah, doing it all basically,

professor, cardiologist.

This year, he published a book called Super Agers:

an Evidence-Based Approach to Longevity,

and that's what we're gonna talk about today.

So, all right, in your book you review

something, like, 2,000 studies on aging.

I was telling him, I was reading his book, and I was like,

Man, this thing is long.

Then I get to the end,

and it's 90 entire pages of citations.

So the homework was done.

In small font, right? In tiny font, yes.

So when I first picked up your book,

I thought it was gonna be primarily about,

you know, those lucky people who live to 100

with minimal effects on their health,

and you do study those to some degree.

What do we learn from them?

Like, what have you been able to say

from the super-agers themselves?

Right, well, it's great to be with you, Sandra.

And I think one of the biggest lessons we learned

was that a health span,

which is, of course, very different than lifespan,

is not very much genetically, genomically determined.

And so when we did a study of 1,400 people,

we called it the wellderly,

we did whole genome sequences on all of them.

And we saw very little difference in their DNA

compared to the elderly,

which is the average person 65

who has at least one major age-related disease.

So we have to get out of our mind that it's a genomic story.

Of course, there's a little bit of that that contributes,

a little bit of luck.

But mostly what we've learned is that the immune system

is the big driver for healthy aging,

and that's much influenced by lifestyle factors

and other ways.

And so we're only now starting

to get a good handle on health span

and also emphasize that much more than lifespan.

So what are some of the big things

with the immune system that we can control?

Yeah, well, lifestyle does influence our immune system.

So a diet that's anti-inflammatory

and very low on the culprits of ultra-processed foods.

The exercise is perhaps the most important of all.

And it's not just aerobic exercise,

but it's also resistance and balanced training.

And then, sleep quality, not so much quantity.

Especially deep sleep when the brain

is getting its toxic metabolites

that are pro-inflammatory to the brain,

getting it out of the brain.

These are the ones that are most highly recognized.

But there are many other factors, like social connections,

being out in nature, what we were just talking about,

so many other things that fit into this,

what I call in the book, lifestyle-plus factors,

because it isn't just the big three, there's many more.

And then, there's the other concern

that are in our environment.

We're seeing the problems with not just air pollution,

but micro and nanoplastics, forever chemicals,

and these things are basically going

in the opposite direction

that are markedly hurting our immune response,

making it more faster pace of aging

and pro-inflammatory,

which is the worst thing we could do

for preventing these age-related diseases.

It's kind of wild to me

that there's so much underneath what you just said

about how, like, social connectivity

affects your immune system.

Like, it's just not a direct line

that anyone would've necessarily guessed.

But I'm curious, just to pick up on one of 'em,

like, the ultra-processed foods.

Like, what is the mechanism

by which that drives inflammation?

Yeah, I mean, it's really interesting,

because what we're learning is the gut brain

and the gut immune system,

it talks to each other.

And so when you ingest really the components of,

it's called Nova class 4,

but the worst ultra-processed foods within that group,

you have a big signal for the gut to promote inflammation.

It talks to the brain, it talks to the immune system.

This is, of course, common to the gut microbiome

and the glucagon-like peptide-1, GLP-1, drugs.

And so it basically is working on that axis

and it is getting inflammation not just throughout the body,

but also in the nervous system, in the brain.

And this is a serious problem,

because the big three age-related diseases,

that is heart, cancer, neurodegenerative,

are mediated by this inflammatory process

and dysregulation, or lack of protection,

of our immune system.

So, unfortunately, our diet has a lot of influence,

and these are the worst culprits.

So what we've seen now for ultra-processed foods,

I think is unequivocal,

is that not only does it increase risk of type 2 diabetes,

but dementia, Alzheimer's, heart disease,

and virtually all the common cancers,

and we're not doing anything about it,

so it's frustrating.

That's something that's hard to control on our own.

We need some help from healthcare policy.

Speaking of healthcare policy,

I mean, do you care to throw out a grade for RFK, Jr.?

Oh gosh. How do you think he's doing?

[audience laughing] Oh. Oh my.

I mean, whatever he calls his campaign,

it's the anti of make America healthier.

It's just today there's,

you know, a AHIP committee

that's taking down children's vaccines,

and he's done nothing to work on the critical aspects

of the ultra-processed foods that he promised he would.

The environment,

that was his original major contribution,

he in fact has done nothing about it,

while, at the same time, the administration

is getting rid of all environmental protection.

So we're going the wrong direction.

And so what's so exciting right now

is that we are going to see prevention

of these major three age-related diseases,

but we're gonna be chasing our tails

because of the environmental problems

that are not being addressed,

and that's really unfortunate.

We could make all this great headway,

and then be held back because of a government

that is basically abandoning the importance

of environmental burden of toxicity.

What would you be doing in his shoes?

Like, what's the number one thing

that you would try and focus in on first

to try and change American longevity?

I think the big thing, of course, as you know,

there's lots going on to try to reverse aging,

and that's great.

But I think what our opportunity right now,

which is unprecedented,

is that we have the capability now

to accept aging

but not accept the aging

of relating to the three major diseases.

In fact, that accounts for about 80%

of the loss of health span.

So the average American,

their health span ends around 63, 65,

because they have one of these major age-related diseases.

Whereas lifespan is 80,

so there's about 15 years.

What we should be doing right now

is health span should be extended

as close as we can to lifespan and beyond.

I think we can do this.

In fact, I'm actually confident over time we will,

because of the new capabilities we have.

That should be the agenda,

that we should have a lot less people

who have chronic disease by age 60-odd,

and we have the path to do that.

In fact, that's really what the whole premise

was in Super Agers,

that this is a unique moment in medicine.

Part of it is because we have multimodal AI,

but part of it is because we have the new layers of data.

We never had organ clocks,

that is the ability to track the pace

of aging every organ of your body,

including your immune system.

We never had biomarkers like p-tau217,

which tells us about our risk of Alzheimer's

10, 15, even 20 years in advance.

And there's just so much that we have right now

to be able to track aging,

that's been the biggest jump in recent biomedicine,

which is the ability to quantify metrics of aging,

which eventually are gonna lead to ways

that will get approval, regulatory approval,

for preventing these diseases.

Yeah, some years ago,

I got a test for, like, c-reactive protein

and it was just like, Oh, you're gonna die tomorrow.

You're done. Get outta here.

And so I hope my insurance company's not listening.

It was a long time ago.

But I wonder with these organ clocks

and other such tests,

is it something where you need to do a whole bunch of it?

Like, that feels very far

from where we are in primary care right now.

Like, what's your idea of how this is gonna play out

and actually get us real data?

Yeah, so, you know, all these years

we've only been treating,

treat, treat, treat,

and now there's almost no prevention of major diseases.

But you do need these layers of data to be able to do that,

to know who is at higher risk,

whether it's for heart, or a particular type of cancer,

or for Alzheimer's,

and we know how to do that now.

So CRP was a primitive marker of inflammation.

Good, good, good. I mean, you could get

a high CRP just from having a upper-respiratory infection

or something like that,

but now these are really sophisticated.

And the organ clocks,

because we know everybody

has a different pace of aging overall,

but now we can go zoom in on any person and say,

Is there one organ that's out of kilter

with the rest of the person's body?

And the other thing that's really fascinating

is, all these years, here it's almost 2026,

we have no way to measure the immune system,

the powerful driver of healthy aging,

we don't have a way to do that in the clinic still.

And so the immune system clock, that pace of aging,

so, you know, instead of a CRP, which was so primitive,

we'd be able to say, Well, Sandra, you're whatever age,

and your immune system is 10 years younger,

that's very reassuring.

But if it's 15 years older,

now you have a risk of cancer,

and you have a risk of these other diseases,

and we have to get on top of that

so you don't ever manifest it.

So it's a whole different world

and that's just the beginning of our ability

to tap into what's going on in any person's immune system.

Let's talk about one of the big new tools

that you zoom in on, which is GLP-1s, right,

drugs like Ozempic.

They've had enormous impact on obesity famously.

But what I find endlessly fascinating

is just all the other indications.

I mean, you've even suggested a future

where we might all end up on GLP-1s at some point,

because the effects are so broad

throughout the body and the brain.

Can you talk about that?

What is it about GLP-1s

that excites you in the context of aging?

Yeah, well, it's a little bit like Lisa Su

was talking about this morning with AI

is that we're in the early innings.

We're still in the early innings of this family of drugs.

There's another eight hormones that we could mimic,

like we're seeing with Ozempic and Zepbound,

that haven't even gotten into the clinic yet

that are potent, even more potent.

And then, of course, there'll be pills and combinations.

So this is an area that's gonna continue to explode.

Now, again, how do these drugs work?

Well, they're signaling from the gut to the brain

and they also talk to the immune system.

So they're the perfect intervention

for bringing down inflammation,

and so what we've seen, of course,

which is effects beyond weight loss,

so the benefit to the heart.

Two-thirds of this has nothing to do with weight loss.

Now, that's a shocker.

We thought, Oh, it's just because these people lost weight

that all their heart indices look better.

No, it's mostly not related to the weight loss.

People's, their inflammation metrics goes down

before they lose one pound of weight.

So there's things that are going on that we see the benefit,

like you alluded to, in the kidney and the liver,

but also addiction.

I mean, that one is still being worked out

is, yes, there's a decreased inflammation in the brain,

but addiction to everything from alcohol,

to tobacco, nail biting,

and then benefits that are even beyond that, like migraine.

Now, of course, the one disappointment

we heard in recent days was about Alzheimer's,

but that was oral Ozempic, which is a much weaker drug.

It doesn't have nearly the potency,

in fact, of other drugs in this family.

But, in addition, they were testing it in people

who already had mild Alzheimer's,

very different than trying to prevent the disease.

So I still remain hopeful

that we will see something in this class of drugs,

when given early,

10 years plus before a person who had a high risk,

that we'll be able to modulate.

In fact, we're gonna start the first Alzheimer's trial

in January to prevent Alzheimer's.

We wouldn't even have conceived that trial a few years ago.

So starting around like age 50?

Yeah. What's your target age

for intervention? Age 50 minimum,

with high-risk features, APOE4 allele,

which is one-fourth of us have that.

A lot of people didn't wanna know it,

because there was nothing you could do about it,

now there is.

Family history, bonafide Alzheimer's,

and also the polygenic risk score,

which is very inexpensive, easy to obtain, when that's high.

Then we can go to p-tau217,

and the first trial we're doing

is to look at the lifestyle-intensive-aggressive coaching

versus just giving educational materials.

And we hope that that will finalize

that lifestyle is important for bringing down p-tau

and changing the brain pace of aging.

Once we see that,

then we have a real signal that we're gonna defer

and potentially prevent Alzheimer's.

GLP-1s, of course,

are complicated, right? Yeah.

Because it's a drug of eternity.

Once you start, you really don't have a path off

if you wanna continue with having seen the good effects.

And, of course, you know, with an aging population,

there's concern about frailty,

and loss of muscle mass, and things like that.

Are, you know, scientists or the drug companies

looking at developing off-ramps

or figuring out a way to make it less of a forever drug?

Yeah, no, this is a real problem.

Some of my physician colleagues say,

Oh, well, that's not a big deal,

you know, we treat hypertension forever,

we treat diabetes, why not this?

But we should be thinking of ways to get people off.

Right now doing that is really not accompanied

by sustained benefit for the most part.

And so there are other gut hormones

that may be helpful in this regard

that are still in the works.

But right now this is, I think, a significant problem.

Of course, one of the issues has been cost,

that's gonna keep coming down.

But still it'd be great if we can avoid long, durable,

or, you know, even permanent commitment

to taking these drugs.

So we'll have to see how this plays out.

But there's a lot of interest

to come up with substitute plans.

We've learned that lifestyle changes

for that year and a half

or two years that you're on this drug,

that can be a great way to get off of it.

But it's very difficult for people to sustain

who weren't in that groove

in the period after getting off the drug.

You're also pretty bullish about AI in medicine.

And what stood out to me

was, you know, AI being able to review medical records

en masse and be able to notice symptoms,

or, you know, patterns and problems

that a physician might struggle to be able to identify.

Was there, like, a single study

that really brought that home for you?

Or how do you think about AI in medicine?

What is it about it that you're like,

Oh, this is actually a real breakthrough for us?

Yeah, no, this is, of course, involved

with this whole process of being able to prevent diseases.

The reason why AI is so powerful

is superhuman vision and interpretation.

So whether it's the retina,

an AI interpretation can tell us

about arteries in the heart,

and kidney, liver, or gall bladder,

and, you know, risk of almost every,

Parkinson's and Alzheimer's

seven years before there's any symptoms.

In fact, we'll use the retina

as a way to know whether our intervention for Alzheimer's

is making a difference.

But other things, like, for example, one of the studies

that was so compelling,

pancreatic cancer is very difficult to diagnose early.

But now we've seen from the whole country of Denmark

and our VA system here,

where if you just put AI

to the electronic records and the labs,

even when they're in the normal range,

it picks up trends years before the symptoms

and the diagnosis is finally made.

So the ability to,

you know, people tend to see,

well, their labs look okay

and the doctor doesn't look at 'em any further,

because there's nothing that's flagged.

Turns out you put your labs to AI,

there's a lot of things that it can detect

for trends that are important to note,

no less our electronic records.

And one of the problems we have is all our images,

every medical scan, not just the retina,

but every type of scan you can imagine,

the AI picks up so much more information that's embedded

that we can never see,

we will never see.

Then, lastly, is the ability

to integrate all these different data sources,

which, you know, we're talking about billions and billions

of data points for any given person.

So this is why we couldn't do any of this

if we didn't tap into AI's potential.

Hmm, we've been talking

about kind of the later decades of life,

but, you know, one of the big things

is also this uptick in cancers in younger people.

What is behind that?

Are you seeing anything in this data

that can help unpack that big problem?

Yeah, and so this is a big issue,

because we keep ignoring the spike that's occurring

in people even in their twenties, thirties,

with colon cancer, breast cancer, and other forms of cancer,

because we've had this very dumbed-down notion

that age is the sole determinant of cancer,

and so screening starts, you know, 40 for mammography,

or 50 for colonoscopy.

These are really not the right way to approach screening.

First of all, mass screening is terribly wasteful,

has a very low yield, lots of false positives.

So what we should be doing is defining high risk,

and that we can determine through genome,

and immune system, and other things.

And the people that are getting affected in their thirties

have the same features of age-related disease,

but we're just not putting them in the mix

of checking these important layers of data.

So I do think part of the problem

we're seeing with young people in cancer

is the exposure to the environment.

The ultra-processed foods is probably contributing as well.

But we're also not screening for people,

because we have so much we've learned from genomics

and from proteomics to do these organ clocks

and body-wide clocks and we're not using it,

and these are really inexpensive.

We can do all of the things I just mentioned

for a couple hundred dollars,

and there's hardly any medical tests today

that you can get for that low a cost.

Before we wrap up,

I'd love to get five tips from the life of Eric, okay?

So you did this big project,

surely you must have been tucking away some ideas

for, like, things you could change, right?

There was that one thing from the WHO

that, like, after the age of 65,

most people have like one healthy birthday.

One. One.

That to me really sank in.

And so what have you done, after all this,

to change your life?

I kind of took a systematic approach.

So I really benefited from the deep research here.

One, of course, was changing

what was a very ritualistic exercise

that was aerobic

to then bring in resistance and balance training,

giving that almost equal weight.

Another was I was not having good sleep quality.

So learning to track that,

and really finding all the things

that were interfering with high-quality, deep sleep,

which is that phase of sleep

when you get these toxin metabolites

out of your brain.

Were you able to figure it out?

Yeah. Okay.

Yeah, it helped.

I mean, I was averaging deep sleep

that was less than 15 minutes a night, which is dreadful,

and now between 45 to 60 minutes, and it's all because--

Didn't seem to slow you down though,

'cause, like, you published, what?

1,300 scientific papers?

So somehow on those 15 minutes--

Well, but now I feel like I have a lot more brain power

from having my sleep that's higher quality.

So who knows what will happen next.

What about, like, time-restricted eating

and things like that? Time restricted eating

is another big feature.

So not only about reading labels to get rid of things

that are alien contents.

And so actually, if you're reading labels,

most of the time, that's already a problem.

But the other thing, of course,

is, you know, eat an evening meal

as early as you can conveniently,

and don't eat anything else till the next morning.

That's intermittent fasting.

You don't have to go to three days and two,

or five and two.

Intermittent fasting is just,

you know, having that long stretch of time

from evening to breakfast.

Any last tips?

Well, I think, you know, lifestyle is really important

and it's the biggest driver we have.

It's inexpensive for extending health span.

If anybody here is not interested

in extending their health span, let me know.

I'd appreciate that.

But we have to do more than that.

We have to, you know, come up with interventions,

whether it's GLP-1 drugs

or many others are in the pipeline.

We have to use multimodal AI.

But eventually what's so exciting

is we're on the cusp of turning around our acceptance

of the major age-related diseases,

and nothing could be more important in medicine,

and I do think it's gonna be the biggest impact ever

of AI in healthcare.

Thank you, Dr. Topol. Thank you.

We're gonna take a break for lunch.

[audience clapping]

Thanks.

Box lunch is available throughout the venue,

so just walk around, you'll find it.

And be sure to check out the science fair

and other activities in the gallery.

Thank you so much.

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