Hey there.
Every Monday in November and December, we'll be featuring our Future of Medicine series, where we'll be spotlighting groundbreaking researchers, cutting edge treatments and diagnostic innovations for everything from heart disease cancer, brain health, metabolic dysfunction, aging and pain, and also sharing breakthroughs in areas like regenerative medicine, medical technology, AI and beyond.
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And today we're bringing you a conversation that could transform how you think about aging and longevity.
So what if you could look 20 years into your health future and prevent disease before they ever take hold?
Having just turned 60, this question feels deeply personal to me.
And the answers that emerge from today's conversation left me filled with hope and possibility.
Think about this for a moment.
Right now, 80 to 85% of people over 65 develop at least one chronic disease.
But so many of these actually begin to build in your 30s, 40s, and 50s.
But what if that wasn't inevitable?
What if we could identify and address health issues decades before symptoms appear, potentially preventing conditions like Alzheimer's, heart disease and cancer, years or decades before they became a part of your life?
My guest today is Dr Eric Topol, executive vice president and professor of molecular medicine at Scripps Research, the largest nonprofit biomedical institute in the United States.
He's also the founder and director of the Scripps Research Translational Institute, a practicing cardiologist and one of the 10 most cited researchers in medicine.
His latest book is Super Agers, An Evidence-Based Approach to Longevity.
We explore fascinating new developments in what he calls super aging, like organ clocks that can measure your biological age and AI systems that can predict health outcomes with remarkable accuracy.
And here's what really caught my attention.
Many of the most powerful interventions, they're simple, accessible things we can all do right now.
Dr. Topol shares how specific lifestyle changes combined with emerging science could help more of us become super-agers, those remarkable individuals who stay sharp, active, and disease-free well into their 80s and beyond.
So excited to share this conversation with you.
I'm Jonathan Fields, and this is Good Life Project.
As we have this conversation, I feel like we're a couple of years past pandemic phase, where a lot of people were dropped into this moment where their heads were spinning.
They got reacquainted with impermanence and mortality.
And people really started thinking again about the state of their lives, the state of their health, their well-being and those around them in a much more meaning, in a real way.
And I'm at an age now, I turn 60.
I am on the precipice of really trying to figure out the next season of my life.
What do I want to be doing?
And also, at the same time, how can I best take care of myself as I move into this next season of life?
Maybe I can make it not just the next season, but maybe there's one after it as well.
So if we zoom the lens out here and I ask you a fairly broad question, How would you talk about the general state of health and aging in sort of the Western world these days?
Well, aging is a natural process.
So the idea that we should be reversing it is not going to be easy, right?
But what we can do is promote healthy aging.
The problem is we're not doing that very well.
And in the U S, for example, people 65 and older.
They have at least one chronic disease, if not multiple.
And I'm talking about 80, 85% of people that age group.
So that's not healthy aging.
That's what we call the elderly as opposed to the welderly.
The welderly super agers are the ones that they're 85 plus.
They've never had any cancer.
They don't have any neurodegenerative disease or cognitively sharp and intact.
And they, have no cardiovascular disease.
Those are the big three age-related diseases.
So we aren't doing well, but I'm actually quite optimistic that we can do far better moving forward.
So you say 80 to 85 of folks, once they hit the age of 65, will have some sort of significant health challenge.
Yes.
That's a huge stat.
Oh, I know.
It's extraordinary.
And it's replicated in many studies.
We have to do better.
We have an aging population.
So that's just going to add to the burden of chronic diseases.
And these, as you say, they're serious diseases, whether it's heart failure Alzheimer's Parkinson's, significant cancers.
So these are the most important diseases of our whole body aging process.
They are tied to aging, each of them.
And we can avoid them in the future.
We can avoid a lot of this burden now, but we're not taking it seriously with the data that's in hand.
As you're describing, that last year I sat down with somebody who's doing some really interesting primary research at Sloan Kettering on cancer.
And during the conversation one of the things that came out, he sort of rattled off a list of significant risk factors, just on a very general basis.
And he said, actually, age is very significant.
He said, basically, turning 60 is one of the most significant risk factors or indicators of cancer.
And I kind of leaned forward in my seat and it caught me that simply turning the calendar brings you that much closer to being at risk.
And obviously, it's not 60 in a day.
We're talking about just generally, but it was jarring for me to hear that.
Yeah, and now we know why, of course.
And the reason why people do well with aging after 60 is that they are not prone to immunosenescence.
That is the loss of integrity of our immune system.
Hmm.
And they don't have inflammation, which is the untoward inflammation in their body and their brain that occurs with aging.
So, yes, it starts to really zoom up at around 60.
It keeps going all the way as we get older.
But some people because of their lifestyle, because of the things that they're doing And you know, perhaps a TED of luck and a small contribution from genetics.
But some people do really well.
That is to avert these risks that are presented because, you know, if our immune system isn't fully competent, that's when cancer can strike, because normally our body recognizes these alien cells and basically squashes the cancer before it can get legs and get into any spread mode.
And that's just one example of how a fully protective immune system is working 24-7 to keep us out of trouble, because our age does pose some risk.
And if you're doing all the right things in your lifestyle and avoidance of some of the environmental burdens as best you can, that's going to really limit the chances for our immune system going haywire or dysregulated or lacking protection.
And I want to dive into what some of those are, but you've used a phrase a couple of times now that I want to understand better inflammation.
Take me deeper into this.
Yeah.
We go back to the immune system.
And these cells, whether they're lymphocytes or neutrophils, macrophages.
These immune cells are incredibly important because they can secrete proteins.
They're known as cytokines or chemokines that take our immune system into full activation mode when we don't want it.
It's not like we had an injury and we want to heal or a wound.
This is when you don't want it.
And it's basically affecting organs, tissue in the body or the brain.
And this is undesirable, untoward inflammation, which leads to tissue injury.
And it could be arteries, it could be the heart, it could be the kidney, certainly can be the brain.
So this, of course, we didn't have a good way to measure that until things were pretty far along.
But now we do.
We have these things called organ clocks.
Organ clocks and inflammation are tied together.
We can look at the pace of aging of every organ in the body and say, huh, it's accelerated.
Pace of aging is faster than it should be in that person by their age. faster than the other organs.
What's going on here?
And say, oh, well, you know, we need to investigate what is leading to inflammation in that organ.
Tell me more about these organ clocks.
Is this a diagnostic testing modality or how do we actually look at this?
Yeah.
I mean, it's something that will be available routinely soon, inexpensively.
It was first developed by the group at Stanford led by Tony Wiskorei, published in 2024.
And up until now we had these so-called body-wide clocks, so-called methylation or epigenetic age, which would say well Jonathan, you're 60 almost, but your clock says that you're actually 56.
That's good.
Okay, that doesn't tell us that much.
But what tells us a lot is oh well, we looked at all your organs and your immune system is at very fast pace of aging.
It's at an age of 70, even though you're supposed to be 60.
So we know that you're likely have one of these age-related diseases.
Now they are derived from.
If you take a sample of blood, just a few milliliters, and you assess up to 11000 proteins in our blood, AI basically has been used to partition the proteins that link to the artery or to the heart or the kidney and the liver.
And that's how we derive these organ clocks, which have now been validated by many groups.
And so it would not be at all surprising, beginning next year likely that people will start to have access to these organ clocks for a low cost.
And I would presume, as we get older, you know, depending on the age and that person's history, that may be something you check each year or every couple of years because you want to find out.
It's like you know, take your car in when it's running okay, but an electronic surveillance says hmm, you know, there's a problem with this tire or this transmission or whatever.
It's like that for our body, but we never had the means to do that until now.
Yeah, I mean, that's incredible to be able to not just get this general feel for okay, so systemically we feel like there's excess inflammation or you're trending towards an older biological age than your actual calendar age.
But you can literally zero in and go organ by organ.
And it sounds like through a fairly straightforward blood test and say okay, we can actually tell you there's something going on in your liver.
There's something going on in your kidney or something like that.
And I'm assuming that this also.
This gives us information, maybe even significantly, before we have any symptoms.
That's right.
That's the critical point you're making.
So each of these three diseases cancers, common cancers, the neurodegenerative and cardiovascular they take 20 years that are incubating in our body before we actually have the signs and symptoms.
And so yeah, that's the whole point is, once you know like, for example, one of those clocks is the immune system clock.
And once you know that that system isn't working like it should because it's aging too fast, then you know you've got a potential problem.
And let's say you had a family history of a cancer and your immune system clock was out of whack, I would be putting you under much tighter surveillance and trying to find out you know, which cancer it is that we might want to try to prevent.
So yeah, this is a whole new.
And, by the way, it's hard to get an organ clock.
That's abnormal if you don't have inflammation in that organ.
So we never had until now an ability to measure in the clinic a person's immune system functionality.
It's amazing.
Here it is 2025.
And it was all a guess.
And now we have a way to do that soon.
And that'll be really important because, as we age, some people's immune system is intact till they're 90 plus and some are starting to deteriorate in their 50s.
This is why it's so important in any individual to get a handle on.
Yeah, and it would make sense, as you were describing, if so many of these conditions start to manifest, potentially up to decades before we're actually aware of the symptoms.
And I guess this is why cancer can sometimes be so challenging, because often it's actually not detected until it's fairly advanced in the system.
But if we can catch these at the stage of inflammation, it's almost like the fundamental phase of dysfunction, before it actually manifests in sort of some physiological change.
I would imagine that most of the things that would pick up would be reversible or treatable.
I don't know how you feel about the word cure, and I think it can sometimes be a loaded word, but at a super early stage.
I'm into prevention.
It's much better than trying to cure once it's already there.
So your point about cancer, the way we try to diagnose cancer today is secondary prevention.
That is, you have a screening system like a mammogram or a colonoscopy or prostate-specific antigen test, and it's abnormal.
Well, you already have cancer by that point.
And now we're trying to basically, as you say, treat it, try to cure the person of the cancer.
And that's the wrong way to go about it when you have all these years to work with and these new tools to pick up the risk in a person, which isn't just, by the way, the organ clocks and all these other things that we can use, like the person's genetics and other markers.
Like, for example, for Alzheimer's.
There's an incredible ability now to know about a person's risk 10 to 20 years ahead of time.
This marker, again, a protein, it's called PTAU217.
If you have a high risk for Alzheimer's.
For example, you had a parent who had this diagnosis.
You have an APOE4 genotype.
One copy, no less two.
You have a polygenic risk score, which you can do very inexpensively.
So we can tell who's kind of at risk.
But then you look at the PTAL 217 and that that's high.
That tells you.
It gives you a temporal link of when you're likely to see some cognitive impairment.
And it used to be, oh, well, nothing we can do about it.
Well, there's a lot we can do about it now, about all these things.
We can prevent, we're starting a big trial to prevent Alzheimer's.
That's never really been done before.
The trials that have been done to date have been people who already had at least mild Alzheimer's.
So this is an exciting time because we're using markers and clocks and proteins and genes to add to all the other layers of data that we have had with multimodal AI.
To then say you know Jonathan, this is the one thing you need to be worried about in your lifetime and we're gonna get all over it, so you don't have that.
And then, added to all this was the most extraordinary thing in the last week was that a paper from Germany was published.
Like you know how you can fill in a sentence with generative AI or write an essay.
Well, we can write your health essay.
We can say now with pretty high accuracy and it's still early now given up until age 59, what are you going to have in the next 20 years?
And just using your electronic records, your notes, self-reporting symptoms along the way.
And that's not even including some of these things that we've just been talking about.
So that was a remarkable study that was done in 500000 400000 people in the UK biobank and 19 million people in Denmark.
So the prediction and prevention world is just lighting up.
And again it's a reflection of the ways that we have now to have insights about a person way in advance of them having an age-related condition.
If I'm understanding right, then this study grossly described could take an individual's medical history and maybe it's going to ask them for a whole bunch of other lifestyle-oriented things.
Load it in and it sounds like you're using AI effectively.
Say okay, based on everything you've given us.
We have the story of your life and your state of health and well-being up until now.
And we can accurately predict 10 years, 20 years, 30 years down the road, Up to 20, incredibly well.
And it's just going to get better.
But what adds to it is that's not even including the organ clocks, the proteins, the genes.
Just with, as you said, some very general questions about the person's lifestyle and their electronic record.
It was amazingly good at saying, here you are at age 59.
These are the things that are going to likely happen.
And not just happen naturally between now 59 and 79, but went heart attack at age 66, mild cognitive impairment at age 78.
I mean, it's a whole new day.
But of course, this is the risk that's being projected and we have ways to mitigate that risk, much of which we didn't have before.
So, just like we've been talking about new ways to pick up the risk of unhealthy aging, We also have risks to mitigate the outcomes that might occur.
So this is a whole new day.
Prevention is becoming a reality.
Instead of reversing aging, it's promoting healthy aging.
It's such a paradigm shift also, right?
Because I think, let's say a generation ago, if somebody would have offered a test that could give you this information, my sense is there would be a lot more fatalism based on this.
And there are a lot of people who say well, that's nice, but I actually don't want to know, because the assumption was there's not really much I can do about this.
It kind of is what it is.
So why would I want to know that in 12 years I'm going to have a heart attack, or in 15 years I'm going to have this type of cancer in my body?
It's going to happen.
It is what it is.
But what's exciting is that this is happening at the same time, from what I'm hearing from you, as us really understanding that if we can catch so many of these things far earlier than we've ever been able to by triangulating different methodologies, also that so many of the things that we looked at as being it is what it is, and all I can do is hope for the best and treat it and maybe
I get through it.
There's so many more of them caught in the very very, very early stages, before they actually even become quote disease state, that we actually can prevent so many of these from unfolding.
Oh, it's amazing.
And also how many people are not aware of the progress that's being made.
So let's say, for example, you have a risk of Alzheimer's disease and you're.
You get a look at the data for just getting a shingles vaccine, which people over 50 should get, but most don't.
Okay,
Now what's amazing is three huge studies, so-called natural experiments, which in many ways are better than randomized trials in the populations in Australia, in Wales and in the US.
They all showed the same thing that people who got the shingles vaccine in this natural experiment they had a 20 to 25 reduction of dementia, most of which is Alzheimer's.
So it's not because it's working on the virus, it's revving up the immune system.
And what would be fascinating is if we could look at the immune system clocks on all these people, because the people who were derived the most you would expect, are the ones that their immune system aging was fast.
So there's no simple thing that you can do.
But once you know and you can dial up or down a person's immune system, that gives us a whole new ability.
So, whether it's in the brain, to prevent inflammation or promote the integrity of the immune system in the arteries, to prevent atherosclerosis and then to keep that immune system on guard so that we don't develop a cancer spread.
I mean, cancer itself won't kill a person.
It's the spread to other parts of the body that is almost invariably leading to the reason why people have so much morbidity and mortality from cancer.
And we'll be right back after a word from our sponsors.
If inflammation is at the root of so much of what we're talking about, is that a fair assumption?
Yes, yes, absolutely, yes.
Okay.
You've shared one or two ways that we might think about helping out.
What are some of the currently available ways that we can look at reducing inflammation and And I'd love to sort of go from everyday available, accessible to anyone?
We can just make these choices in our own lives to okay.
We actually need some help or some intervention or a script written or something like that.
What are some of the big things that jump out?
Yeah.
So I spent a lot of time in the super agers book about this, which is let's start with what you eat.
Okay.
First of all, you obviously don't want to be heavy overweight, if you can avoid that, because in your belly fat, no less other fat in your body, but especially in the belly that is pro-inflammatory.
The fat cells are like a machine, producing so-called adipokines, these proteins that promote inflammation.
So you don't want that.
But then what you eat?
You basically wanted to cut down your ultra-processed foods, particularly many that are the real culprits in that category, these alien foods that should never have been in our food products to start with, that promote inflammation.
Can I ask you a question about that also before we even move on?
Because I think we've all heard this over the last few years.
You know ultra processed.
Try and remove as much from your diet.
What is the link between that and inflammation?
How does the high level of processing in a food lead to inflammation in the body?
Yeah, well, it's the same thing as we've been talking about.
Once you get these foods into your body, particularly on a chronic basis, I'll give you an example.
There's a fellow named Chris Van Telleken who's a physician scientist in the UK, and he wrote a book called Ultra Processed People.
It's a very compelling book, and I've gotten to be friends with him.
And in the book, he tells a story about of an experiment he did by himself.
He was concerned about ultra-processed food, but he wanted to see what it would do to him.
So before he started on a, it's kind of like supersizing the guy that ate 30 days of McDonald's foods.
Well, he ate 30 days of high-content, ultra-processed foods, the things that you'd find the junk foods, the things that have all these things to promote rapid absorption and texture, so that they're essentially addictive foods that you gain weight and want to eat more.
It's like that old commercial about the potato chip, but you can't eat one.
Well, this is like...
So anyway, he did this, but before he started the 30 days he had a brain scan and he had all his inflammation proteins done.
And after 30 days, he gained almost, I think it was 20 pounds.
His brain became inflamed on the scans, MRI, and his proteins in his blood went through the roof.
Now that's just an N of one, but it's replicated across many studies that have been done that these are very unhealthy foods that promote inflammation throughout the body and we should be outlawing them from our food.
There's a group, it's called Nova, Class 4, which are these alien things in our food, and some of them are okay, some of them are just the worst, and we should be taking out the ones that are really unequivocally linked to promoting inflammation.
But if you avoid things that are in packages, that's one way, and boxes that's what they're usually found.
If you eat fresh foods.
And, of course, the other thing besides ultra-processed that promotes inflammation are things like red meat fried foods.
A lot of things that we know are not so healthy, but now we know that they're promoting inflammation.
So a healthy diet which is largely plant-based can have, obviously seafood, small quantities of red meat, but largely plant-based, that rich in vegetables legumes nuts, things like that.
That is the Mediterranean or Mediterranean like diet that is anti-inflammatory.
So it reduces inflammation in the body.
And so does exercise and sleep help.
These are the most simple, relatively low cost to free ways should be available for everyone to reduce the level of And, in fact, not so much that they're promoting inflammation, but they're inhibiting it.
And so, as we go from what we eat to, let's say, how we exercise, more exercise helps to reduce body-wide inflammation and promote integrity of the immune system.
Before we drop entirely into exercise, there's one thing that's sort of like a flashing red light in my mind on the nutrition side.
There's been a lot of attention over the last few years in particular around our need for protein as we age.
And there are a lot of proponents that say like we are getting a tiny fraction of what we actually need.
And they cite research to support it.
And some of these people are like well-regarded academics and also primary researchers.
You have a different take.
And tell me if I'm getting this right.
I think I've also heard you talk about a potential link between high levels of protein inflammation in the body.
So give me your lens on this.
Yeah, I went in depth on this both in the book and a recent Ground Truths substack of all the data that we have about protein intake.
And so, if you review all that data, these people that are proponents of taking very high amounts of protein, like one gram per pound
These people have no basis for that recommendation.
But if you look at the data, there are no data whatsoever beyond 1.6 grams per kilogram.
The current recommended daily allowance is 0.8.
And most of the studies come in at 1.2 grams. to 1.4 is okay.
There are studies to show, and also in experimental models, that going above 16 like, for example, we're talking about a person who's let's say, if there's a person who's 150 pounds, right.
According to the one gram per pound, they'd have to take 150 grams of of protein a day.
That's a lot of protein.
And, by the way, most of the excess that you take in that your body can't use that day are just beat out.
You're basically spending a lot of money.
You're adding more calories to your intake.
And what are you getting out of it?
Nothing.
But if you're taking in particularly too much protein and it's animal derived and we learned a lot about leucine, one of the essential amino acids, which is derived mainly from red meat then you start to see this pro-inflammation effect.
It's really dangerous.
So not only are you... prone to losing that extra protein.
There's no way it can be stored.
But now you're also making things worse with fostering inflammation.
So if you look at everything that's available today, you'd say okay, maybe the 08 is a little conservative.
As you get older, maybe you need a little more protein.
You want to preserve muscle mass.
But we don't have anything to go.
Certainly above 16, which is doubling the recommended daily allowance, and certainly a 50 increase at 12 grams per kilogram.
And, you know, you don't have to then spend your life, how can I get more protein?
I got to get my, you know, 200 grams.
I mean, this is crazy stuff.
It's an obsession right now.
And it's been heavily promoted.
And unfortunately, some of the people promoting it have obvious major conflicts of interest.
And that isn't good.
You know, if you look squarely at the data, you'll say OK, it's OK to increase your protein a small amount.
But let's not go crazy here because there aren't data to support such mega intake of protein.
I think it's a real mistake and it could be injurious.
I think the argument that I've heard in favor of it is that by the time you're in the middle years of your life, we all start to experience some level of sarcopenia, some level of just natural shedding of muscle tissue.
If you want to sustain your mobility and also this highly metabolic tissue in your body well into your later years, that your body also requires higher levels of protein in addition to resistance training.
It's not just about what you take, but actually using like, creating a need for uptake of it, in order not only to maintain what you have, but to stop or slow the reduction of what you have.
Is that not right?
No, it isn't right, actually.
That's rational, you would think, right?
It turns out, the resistance training is the key, not so much the So the studies in older people, 70 and older.
There's been a few good studies there and they looked at resistance training as the driver of preserving muscle mass.
Regardless of protein intake.
Right, right.
So in fact there's even debate in some of these studies whether they should increase protein in older people.
I think it's fine.
I've certainly increased my proteins in tune with your point, but I'm relying and I think we should rely on the data and the evidence, which requires work.
It isn't just like something you're eating.
You've got to do the work to have strength and resistance training.
But yeah, that's what drives the avoidance of, as you say, sarcopenia or loss of muscle mass, which does happen as we get older.
Variably, but it's something we want to avoid because then you're much more prone to injury.
And also doing strength training, just like aerobic training, helps to promote immune system health and ultimately reduce inflammation in the body.
So these are really important things to pay attention to.
And just the notion that actually there is the potential for very high levels of protein intake to increase inflammation in the body.
And I guess it really depends on I'm guessing it depends on the individual, their response to it, how much they retain and what the type of protein is that they take in.
That's right.
I don't think I haven't heard before this idea that increasing protein it's not just a matter of well.
You're wasting your money or you're peeing it out.
It's actually, if in fact does in your system lead to increased inflammation, you're effectively increasing your risk for all sorts of diseases.
Yeah, exactly.
And that's why I think, as you say, it is certain proteins.
And recently the group from Washington University certainly found that leucine was a major culprit that promotes this inflammation.
They found the mechanism for it.
So yeah, I think we should be very leery about too high a protein.
And there's so many products now that are being used as supplements like bars.
Turns out, the bars are unprocessed, ultra-processed food, which is a potential double whammy if you're getting ultra-processed foods and you're getting too much protein.
But powders and all these things, they're just not necessary in most people.
So it's a fad.
It won't last because the data doesn't substantiate it.
And there is some risk and certainly unnecessary expense.
And one of the things you asked about early on is something we all can do, that isn't costly.
And that's what I'm trying to outline is things don't waste your money on things that don't have any proof.
So exercise.
It sounds like, as we were just talking a little bit about resistance training, being really important.
Other forms of movement
And actually let me ask you are you aware of or is there research connecting resistance training to inflammation?
Yes.
What's interesting is, when you are doing a workout whether it's aerobic or resistance you will get a small amount of inflammation from that workout.
But what it does is it primes your body and it increases its ability to prevent over response.
That is, you know, too much inflammation.
It's basically promoting the health of the immune system and the lack of an unleashed overreactive inflammation response.
So it's like a training system for your body.
Yes.
And what's interesting is aerobic exercise. and resistance training complement each other.
They're two different ways to get your immune system and your prevention of inflammation into the highest level of functionality.
It sounds like it's kind of like this two-sided thing where exercise in almost any form at the right level of intensity is going to create a short-term bump in inflammation.
But the more chronic sustained effect is, it's going to help more consistently allow your system to have a lower, just more pervasive set point for inflammation.
Yeah, no, that's it.
I mean, just consider that you're doing a little mini stress test and your body just is getting so adapted adaptive to doing this, so that when you really do have the real deal, you don't have adverse response, a chronic adverse response.
So it's just priming your body to have a very beneficial type of response.
Yeah, it almost sounds like exposure therapy or immunotherapy.
It's like a little bit, a little bit.
It's like the classic allergy shots.
You get a tiny little thing once a week for a couple of years and over time it just allows your more systemic reaction to just calm down because it's now used to it.
That's a good analogy.
Yes, definitely.
Sleep you brought up also.
This is something that frustrates so many people.
And I think in no small part because they feel like they've all heard the classic sleep hygiene things.
And yet they feel like I just have so little control.
Everyone talks about how important it is, but I feel like I have so little control over it.
Yeah, well, it turns out they have a lot of control.
One of the biggest things is sleep regularity.
So going to bed ideally around the same time every night. and waking up around the same time.
Our body needs its circadian rhythm, but we don't respect it.
And so it's totally under our control for the most part.
I mean there may be reasons why you're up at occasional night, because you're whatever social obligation or something fun.
But for the most part, we have control of that sleep regularity.
It has an amazing correlation with cardiovascular outcomes, cancer, and neurodegenerative diseases.
So that's one thing, one of the biggest things, and that is fully under our control.
The other thing is that you want to get as much deep sleep as possible, because that's when you have your glymphatics of the brain wash out your metabolic waste products each day that you accumulate.
And those are pro-inflammatory.
They're toxic and you want to get them out of there.
Now, it turns out you exercise, especially not late in the day.
That helps.
You eat, again, not too late and you're having a healthy diet.
There's interactions.
You drink a lot of alcohol.
That's bad because that tends to interrupt your deep sleep.
If you are getting up at the night, during the night, because you're having to void a lot, that's not good because that's interrupting your sleep, potentially early in the night, especially hurting your ability to get into deep sleep and stay there.
And so hydrating earlier in the day rather than evening is important.
So there's a lot of things we can control.
You don't want to take Ambien, of all things, because Ambien backfires.
Instead of helping to promote the washout of these waste products of the brain, they go backwards.
More it's kept in the brain.
So, even though you may feel like you got some sleep, it didn't help you at all with respect to the major function of rejuvenating and getting rid of your brain waste metabolic products.
So there's so much you can do to get into sleep health that is going to promote.
And it used to be thought, oh, you got to get eight hours of sleep, seven hours of sleep.
No, much more important is how much of that time did you get is deep sleep?
Because you might even get six hours, but if you had an hour plus or more of deep sleep hey, that's great.
And we can track that now.
We have lots of ways to get pretty accurate readings about that.
We'll be right back after a word from our sponsors.
If we start to cross the spectrum from lifestyle you actually described lifestyle, plus some things we haven't even talked about, like relationships stress, environment toxins.
I think these are all things that are additive.
If we start to cross the spectrum of moving out of lifestyle but more intervention.
One of the categories that I think I'm curious about is pharmaceuticals.
What are we seeing today?
Are there any big levers that are really helping with super aging?
Yeah well, I think the one that's emerging, which is just not expected but looks like it's going to have more impact than ever conceived, is the GLP-1 drugs, like in the Ozempic family.
What I would contend is that we're in the early days of this family of drugs.
There's about 10 of them that are beyond ozempic and ZEP-bound, not just for, of course, diabetes and obesity, but we're seeing the effects of these drugs on the favorable effects on the kidney and the liver and the heart and arteries and migraine and rheumatoid arthritis.
And I mean, but they... are anti-inflammatory drugs.
They're the most potent anti-inflammatory drugs that we have, general purpose.
They work at the brain and in the body.
OK, so they're not monoclonal antibodies that somebody with rheumatoid arthritis or psoriasis might take.
These are general anti-inflammatory drugs that if you take it for obesity, you see the inflammation markers are going down before you lose any weight, which is quite striking.
We'll have to see how this plays out.
But right now we're looking at a drug class with 10 more entries. of different receptors that can be put in combinations in pill form rather than injection, hopefully, you know, generic, very much lower cost.
What's amazing, Jonathan, is the gut talks to the brain and it talks to the immune system.
And it's the brain and immune system which, by the way, there's a lot of crosstalk there which have just amazing modulation by the gut, whether it's through these hormones, which basically these are gut hormone memetics, or through the gut.
Microbiome used to be, the adage was a way to, a man's heart is through his stomach.
And now I would say the way to a person's health during aging is through their gut.
Whether it's the current gut hormones or the ones to come, or working through our gut microbiome, these are having big effects of blocking, suppressing inflammation and promoting the health of our immune system.
It's fascinating because we had, I think a lot of people don't realize GLP-1s are not actually new.
They have been around for quite some time.
There are newer generations that are more tolerable.
And now there's more research being done and they're becoming more widely prescribed, because I guess the research is starting to show really interesting results across such a as you were describing such a wider spectrum of things than we realized.
Do we actually understand how they work at this point?
Yeah.
Well, first of all, I have a chapter in the book where I go through the history.
And, as you point out, these drugs the first one was approved over 20 years ago, but they thought they should only be using people with diabetes type two diabetes
And that was the way it was for most of two decades.
And no one had thought about obesity because of note.
The people who took these drugs for diabetes didn't lose much weight, a few pounds.
So When Novo Nordisk, the first one out with these drugs, was thinking about should we test an obesity?
I said, why would we do that?
We've got tens of thousands of people.
They didn't lose any weight.
Well, there was a scientist at Novo Nordisk named Lata Knudsen who was awarded a breakthrough prize.
I was on that committee, and we had to review all the documents in Danish, and it was wild.
She was the one that pushed Novo Nordisk to go to obesity and take up the dose, and now even being tested to prevent Alzheimer's progression.
So we have learned a lot and people can lose a lot of weight.
And there's even another triple receptor reseratide, that people just don't ever stop losing weight.
It's crazy, you know.
The others they plateau.
But this is powerful stuff and I think The mechanism you're bringing up, beyond the things I mentioned, they do.
What was surprising is they block the interest in alcohol intake.
They stop in a large proportion of people addiction to things like gambling cocaine, other drugs, nail biting, you know.
So how does this work?
Again, the brain inflammation, the circuitry in the brain that is telling us we should eat or that we're addicted to things.
These are getting basically rewired with these drugs by knocking down inflammation.
The studies that have been done in the animal models.
Because you can't do these in people, you can't get the levels of inflammation in the brain very readily, but in people, in models, you can't.
And it's striking how much reduction of brain inflammation is occurring with these drugs.
Now, beyond the specifics of the mechanism, like you know nitty gritty about how is it achieving this inflammation reduction in the brain?
It's a little tricky because, For example, Ozempic doesn't get much into the brain itself because of the blood-brain barrier.
But what it does is it activates the vagus nerve, and it has a lot of this gut-brain action.
And some of the newer drugs in this family... have much better penetrance directly in the brain.
So whatever we're seeing now, you know, most people who are on GLP-1 drugs say their taste for foods has changed.
Not only it's reduced, but they want to eat healthy food.
And the companies are now struggling, the oligopoly of food companies.
How are we going to find foods that are addictive to the people taking GLP-1 drugs because they don't like ultra-processed foods now?
This is wild.
We're still going to learn more, but what used to be thought was the mechanism of these drugs of slowing motility in the stomach and the GI tract, giving a sense of satiety.
That's not the predominant mechanism.
Benefit
The benefit is much broader and likely very much localized to the brain.
I mean, it's really fascinating.
You also wonder whether change in the brain is reducing the desire for behaviors that would lead you on to engaging behaviors or taking certain foods that would then lead to inflammation from those things.
So it's almost like there are multiple pathways, in fact.
On the one hand, it's... acting directly on the brain, on inflammation within the brain.
And secondarily, it's causing a change in behavior which stops so many of the things that would cause inflammation from the outside in.
Yeah.
Not to mention losing weight, particularly belly fat.
You're getting rid of that source of inflammation, that whole machinery.
So yeah, lots of different ways that you're following into this common pathway.
The less body inflammation, the less brain inflammation, the better.
Right.
So interesting.
And, as you said, also like we're having this conversation at a time where yes, these have been around for two decades, we're multiple generations past the original class of drugs, but we are still, it seems, still fairly early in the research, especially in the context of all the different things that are being claimed.
It's effective for now.
Yeah, I mean, we got all these other gut hormones to work with and the combinations.
You're starting to get to all these amazing not infinite, but a very large number of shots on goal to achieve desirable improvement in health in the years ahead.
So a lot of excitement, and the fact that we can see these being turned into pills rather than injections makes them even more, not just because it's easier to take a pill, but also because you can get to much less expensive small molecules instead of the peptides, which are much more expensive to make.
So the only tricky part, Jonathan, is that how do we get off of these?
Once you have all these desirable effects, what can you do to keep your inflammation low and all the beneficial effects?
Now, some of the physicians I talk to say, so what?
We give insulin to people with diabetics.
We treat hypertension for the rest of the person's life.
And I say, well, no, I don't want a forever drug.
I want a drug that you could take it for a year or two and then find ways to get those beneficial effects, but not have to rely on yet another drug.
So I hope we'll find ways to simulate this without having to commit to a forever drug.
Yeah, it is a real interesting question.
And I guess we're in the I don't know phase, but I think a lot of people are thinking about that.
Is this something where I start?
You know you start in your early 50s or late 40s and this is just like a statin or something like that, where it just this is what you take for life.
And I think a lot of people are freaked out by that.
But they're not freaked out by the other things that they say, like they take for life, which is a really interesting phenomenon.
Maybe it's just because it's so new and so almost like overtly, you can overtly observe the effect for a lot of people.
Like you can actually see the effect, the changes in your body and in your behavior and in psychology and the way you feel differently.
In a way that other people you know, if you take statins or blood pressure medication, you're not really feeling it or seeing it the same way.
Right, exactly.
I mean statins are one of the most widely prescribed medicines in the world, and certainly in the US.
And the level of... anti-inflammatory impact of the GLP-1s make statins look weak.
I mean, you know so the fact that we got to this, you know tens of millions of people taking statins eventually pills, of course, not injections And we now have 15 of Americans are taking some type of GLP-1 drug.
Some of them are making up their own doses, which we don't even know if it works.
But it wouldn't be surprising eventually that this is considered a very exceptionally common preventive medication and leads to other paths for preventing the diseases that we've been talking about.
Yeah.
And I think more broadly.
The argument I've heard is that we exist within a food system where effectively, billions or trillions of dollars are spent to make the most palatable foods on the planet that aren't necessarily the healthiest.
And also, I don't want to go to extreme here and say you should never have any stuff like that.
No, no, you can't do that.
If you want to eat the cake, eat the cake, and then go and eat healthy for after.
Because I think that's one of the other things.
I've heard people say, look, these sound like miracle things, but also, I like food.
This is actually a source of pleasure in my life and I don't want to remove it as a source of pleasure, which is an interesting argument.
I'm with you.
I don't think that there needs to be anything extreme.
But the awareness should be high so that you kind of come up with that moderate reduced formula that works for you.
We're not trying to ruin anybody's happiness, but we are trying to knock in some of the latest evidence of what promotes health and what doesn't.
What are you looking down the pike?
So a lot of these things are here.
They exist now.
We've talked about everything from largely free lifestyle choices that we can make to some interesting other interventions.
What are one or two big levers that you see that either exist now but you think they're going to be substantially different, or maybe they're coming down the pike.
You're starting to see the research done on them.
They're not available to us now, maybe in five, 10 years, but they have the potential to be game changing in the context of longevity.
Yeah, well, I do think the organ clocks, including the immune system clock, fits in that.
I do think the PTAL 217 and other protein biomarkers fit into that.
The biggest problem we have right now Jonathan, is that we know what helps people generally, but they don't incorporate the things that we've been talking about.
Maybe the people that listen to your podcast are into, but we have 75 of Americans who don't even get the a minimum physical activity on a weekly monthly, yearly basis, right?
So how do we get people to move more which you know of anything that's like the top of the list to do these things we've been discussing?
I think the biggest thing that is different now is that, instead of giving population-level recommendations, which people tend to dismiss that that's not about me.
To get very specific, individualize.
So we say we talked about these AI models that will predict your health future and say these are the things that we want to prevent in you and these are ways we can do it.
And many studies suggest that when a person is specifically their data, their story and you're coming up with things for them, that person, they're much more likely to adopt healthy things.
So I think that's going to be one of the ways that we go after the use of not just these lifestyle factors plus factors, as I call them, because there's so many more than the three that we delved into more but getting people to use those.
Like, for example, let's go back to the Alzheimer's for a moment.
This P-tau-217, when it's high, it indicates very high risk of Alzheimer's.
And it's amazing because it's a simple blood test.
It's not expensive.
And it's been available for two years in the US, but people don't even know about it.
Anyway, if you exercise, you lose weight, you eat healthy, your P-tau-217 drops markedly, 50, 70%.
Well, That's going to correlate with much less chance or deferring the risk of Alzheimer's out by years.
So then we go back to that AM model and say you're now thinner, you're eating a healthy diet, you're exercising a lot more all these things.
Now, when are you going to get Alzheimer's?
And instead of age 72, it's 88.
It's like, wow.
So reinforcing with data, with these tools that we have, is going to get people, I think, much more on board.
Now, is it going to help everybody?
No.
But when you consider how many people are not doing just motion, no less diet and sleep and all these other things, I think we can do better just with that.
And then when you add on drugs and it won't just be GLP-1 drugs, it'll be many others anti-inflammatory drugs that are being pursued right now.
Drugs that will have vaccines that will rev up our immune system that are not tagged to a pathogen.
It's just that we want to give you a vaccine to get your immune system amped up, for example, or to take it down if it's too hyperactive.
So the fact that we have all these new capabilities is extraordinary.
And that's what I'm excited about and specific to the person.
That's the key.
I remember hearing the term precision medicine probably a decade ago.
It was tossed around here and there, and then I really didn't hear much about it.
And it's like, this is the promise, this is the future.
And it sounds like we're circling back to that.
We're now finally starting to get a level of specificity where we can take somebody and use some of these different testing modalities and AI to and be able to really sit down with somebody and say okay, so I'm not going to talk to you about the general risk of somebody, your age, at your weight and your height, with your background, for all these different diseases.
I'm going to talk to you about you.
We just did this testing.
And here's what I'm going to tell you.
Based on this, In three years, you're going to have this type of cancer.
In six years, you're going to have this heart attack.
In eight years, and this is in general population.
I would have to imagine, from just a motivating behavior change standpoint, that that would be much effective.
If you're saying like this is specific to you,
I'm not talking about a general person, your age and your profile.
This is you.
And I can predict this with a high level of accuracy.
That would freak a lot of people out.
Maybe on a level that would actually lead to real change.
I do think it will.
This precision medicine term grew from almost two decades ago, and we haven't really hit it.
And in fact the term is poor, because if you make the mistakes over and over again, that's very precise.
The same mistake.
We need accuracy.
And now we're getting it.
And one thing to emphasize people have there's like a backlash against AI for various reasons right now.
A lot of people are anti-AI.
I get that.
But the point is here that you can't take billions of data points of a person and analyze it with a human expert.
You need ai's help.
And this is where it's sweet spot.
It doesn't hallucinate, it's giving you and it's just going to get better and better as accurate a prediction as we have.
It never be 100, but it'll be, you know, certainly 80 85, 90 accurate, and they keep getting better.
So that's where we are now.
I think it's very exciting because you would prevent diseases that otherwise would occur in a person.
How much does it cost to treat these diseases once they occur?
How much morbidity and quality of life is compromised?
No less the cost.
So our incentives for promoting prevention and the things that a person would do, we should go all out on that, because you know just one person that has to be in assisted living for Alzheimer's for many years.
Just think how much the cost of that.
Or one person that has to get these cancer drugs that cost hundreds of thousands of dollars, that extend life for a few months.
What we're doing with our treatments isn't great, but what we can do with our preventions is extraordinary.
I want to ask you about one other thing before we wrap up.
So much of what we've talked about is really exciting, really innovative.
It's cutting edge.
And also some of it is just basic.
It's accessible to anybody.
I think accessibility is an issue that tends to come up when we talk about future of health oriented topics.
Well, and the question often becomes well, You're like well, that's really nice if you have the money to X Y Z, but my insurance won't cover that.
Or I'm in a medical desert where I don't have access to healthcare I need.
When we're talking about a lot of these things, how do you think about equity and access?
How do we avoid a longevity divide?
Yeah, this is essential because these biotech companies, who I admire, they're trying to find ways to reverse aging.
They're largely funded by billionaires who are interested in preserving their you know not immortality and healthy aging forever.
Whatever they come up with, I hope they're successful.
Some of them are very elegant strategies, but are they gonna be available to people who are indigent, who are not in the highest socioeconomic strata?
No, not now.
On the other hand, what we're talking about is largely either free or such low cost that it should be paid for, because if you can prevent these diseases, what a bargain.
I mean, what a bargain to know your organ clocks or your P tau 217 or your polygenic risk.
You could do all three of those for less than $100 for the cost of the work.
So The problem?
We have Jonathan, to be simple about this, in the United States we don't have a population health system.
We have a fragmented care system, which is different than the rest of the world, okay?
The rest of the industrialized world and all the other wealthy countries in the OECD.
They all are interested in keeping their whole population healthy.
And for them, these strategies work because small costs up front to prevent big diseases downstream.
So equity can be promoted with these low-cost strategies everywhere.
In the United States, we're not positioned well.
It'll be the people who have insurance.
It'll be the affluent.
Unless we do purposely and I make a big point about this in the book.
If we can extend healthspan markedly and it only helps the affluent, what have we done?
This has to be done for everyone, irrespective of their ability to access or afford it.
And I hope that we'll pursue that.
Yeah.
And I think, hopefully the more the research comes in and shows how effective new diagnostic methodologies, new treatment methodologies are and how even just getting really precise with individuals can motivate behavior change, that the data convinces particular insurance companies, the broader industry, that it's worth investing in the prevention side of this.
Because If we can do all the things that we've explored in this conversation long before it turns into something much more serious, I mean even just from a bottom line standpoint, even if you don't care a whole lot about ethics or morality and society-wide outcomes, dollars and cents, I got to imagine it's good business too.
Oh my gosh, yeah, absolutely.
The problem we have.
We rely on these insurance companies And they don't have any guarantee you're going to stay with them.
So they don't really care about long-term protection, prevention.
They just want to know what costs are going to eat up their policies per individual.
So we're not set up right.
Everywhere else is set up really well.
Let's see if we can pivot on this because it's an opportunity that might not come again.
One last thing is, as much as people say AI can promote accuracy, AI can promote better patient-doctor relationship, if we were to fast forward 10, 15 years from now, I believe that The biggest contribution of AI won't be that it discovers new drugs, but it propels this whole prevention, primary prevention, preventing diseases that we never were capable in an individual at high risk to prevent.
We've never done that in medicine.
We've talked about it forever, but we are now at the threshold of being able to do it.
And that's, I think, simply remarkable.
Yeah, that would be an incredible thing to see unfold and to be here for.
Sounds like a good place for us to come full circle in this conversation as well.
So, in this container of Good Life Project, if I offer up the phrase to live a good life, what comes up?
Well, I mean, obviously there's things like having a life with your family and a purpose, and you know the things that you are giving you the greatest fulfillment, and certainly family and purpose are up there.
But I think what most people find precious is a healthy life throughout to a ripe old age.
I'm confident that eventually we'll get to 85, 90 plus the ways to get there healthy.
And what's great about that is, with that, people have more time with their families and their close friends, their social group.
And in addition to that, they'll have more chance to have their purpose fulfilled.
That is, they may work longer in their work or they may, after they retire, go into another phase of.
So I think this is exciting in that respect too, because a good life, they're interdependent.
The things that we most cherish about our family and what we've done to make the world better can be extended and amplified.
Thank you.
Hey, before you leave, a quick reminder that this conversation is a part of our special future of medicine series.
Every Monday through December, we're exploring breakthrough treatments, diagnostics and technologies transforming medicine healthcare from cancer and heart disease to aging, pain management and more.
If you found today's conversation valuable, you won't wanna miss a single episode in the series.
Next week's conversation is with Dr Charlotte Bleas, where we'll explore why doctors can only keep up with 2 of new medical research on how AI could transform not just diagnosis but the entire doctor-patient relationship.
Be sure to follow Good Life Project wherever you listen to podcasts and catch every conversation.
Thanks for listening.
See you next time.
Thank you.
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Until next time, I'm Jonathan Fields, signing off for Good Life Project.
