The Real Reason You Age (And How to Slow It Down) with Dr. Eric Verdin

Mark Hyman, MD

Full Transcript

Automatically generated. Please forgive any typos or errors in the following transcript. It was generated by a third party and has not been subsequently reviewed by our team.

Dr. Eric Verdin
What really has changed in the last twenty years is that we can change your biological age to some degree. Your cholesterol level is seven times less important than your age. So imagine now that we're targeting aging, what it's going to do in terms of impact on your risk for

Dr. Mark Hyman
heart disease. You say that the phenomena that drive aging is primary. The diseases are secondary.

Dr. Eric Verdin
Aging is the biggest risk factor for a whole series of conditions that we call heart attack, stroke, atherosclerosis, many forms of cancer, type two diabetes, Alzheimer's, Parkinson's, all of these diseases. And so it really changes the paradigm of the way we've been taught medicine, is to respond to all of these emergencies that occur, what I call whack a mole medicine.

Dr. Mark Hyman
If we targeted the underlying mechanisms aging, we could extend like by thirty or forty years. So what do you do for helping your immune system age well?

Dr. Eric Verdin
That's really the way medicine is going to change.

Dr. Mark Hyman
Doctor. Eric Burden is president and CEO of the Buck Institute for Research on Aging and a globally recognized leader in aging and science, a physician scientist with over 300 publications. He studies the intersection of metabolism, immunity, and longevity, helping shape the future of how we understand and treat longevity. Eric, welcome back to the podcast. So good to have you again.

I love talking to you. You're my favorite longevity guy because you're like the legit guy. Thank you. You do the studies. You publish hundreds and hundreds of papers.

You do the real science. You really understand this field more than I think most people out there. And you you're willing to explore the margins and edges, which is great, but you're also kinda holding us to the truth, which I really appreciate.

Dr. Eric Verdin
I'm delighted to be here, and I'd like you. I'm a physician. So I think Yeah. You know, I I think it takes it takes for us to have gone through the root of what it means to deal with real lives Yeah. To understand the implications of any statement that you make.

And so, you know, some a number of people have taken to calling me the grumpy man

Dr. Mark Hyman
of longevity medicine. Don't see you that way.

Dr. Eric Verdin
And I and I I take this as a badge of honor because I would rather be sort of a little more conservative than a little more adventurous.

Dr. Mark Hyman
Yeah. And I agree. I if I really wanna know about something, I I ask you. So with that said, you know, one of the things I really love about your framing of longevity, because you're you're at the Buck Institute on Aging, is the framing around disease and aging. You're you you say that the phenomena that drive aging is primary.

The diseases are secondary. And that if we can attack the primary features of aging, which are not necessarily all inevitable, that we can change the trajectory of disease in a far greater way.

Dr. Eric Verdin
I love that you asked that question because it's a concept that came out of the Buck Institute. It's so it's a it's a scientific term. It's something we call the geoscience hypothesis. And it was, published about twelve years ago by my colleagues. Gordon Lithgow was the leader of this, and it hasn't been paid attention enough.

So I will I will restate what it is. Aging is the biggest risk factor for a whole series of conditions that we call heart attack, stroke, atherosclerosis, can many forms of cancer, type two diabetes, Alzheimer's, Parkinson's, all

Dr. Mark Hyman
of Osteoporosis. These

Dr. Eric Verdin
osteoporosis, macular degeneration, sarcopenia, the list, you know, the list go your response to COVID nineteen, your response to Exactly. Pneumonia. All of this is driven by aging. Now when I went to medical school, which was already a long time ago, we were told, for example, for heart attacks.

Dr. Mark Hyman
I think we're doing pretty good for a couple old guys.

Dr. Eric Verdin
And this work actually is helping. There's a sense of urgency there. You know, when you think about this, and how medical school for heart attacks, the risk factors most people can actually recite the risk factors. Smoking, physical inactivity, obesity, and so on. Those were in a box in my in my textbook of medicine as a modifiable risk factor.

There was another box which was the unmodifiable risk factor, and that was your age and your gender. Now we're we're changing both. And so but your age, what really has changed in the last twenty years is that you we can change your age to some some degree.

Dr. Mark Hyman
Your biological age.

Dr. Eric Verdin
Your biological age. Your not your chronological age, you know, how many years you've lived.

Dr. Mark Hyman
But I'm waiting for that.

Dr. Eric Verdin
Yes. But so that

Dr. Mark Hyman
Time machine.

Dr. Eric Verdin
That changes that whole equation because what people fail to recognize is, you know, imagine your cholesterol level, $20,000,000,000 industry with statins, you know, a lot of success actually at mitigating, decreasing the risk for heart disease. Your cholesterol level is seven times less important than your age. So imagine now that we're targeting aging, what it's going to do in terms of impact on your risk for heart disease. Now the beauty of the system is that you're not only affecting heart disease, you're affecting

Dr. Mark Hyman
Everything.

Dr. Eric Verdin
Everything. And so it really changes the paradigm of of our the way we've been taught medicine, which is to respond to all of these, emergencies that occur, what I call whack a mole medicine

Dr. Mark Hyman
Yeah.

Dr. Eric Verdin
Where you you have a heart attack, we serve we survive, we cure cancer, and so on versus targeting the root cause. So think about a tree with all of these branches being diseases. Now we're going for the core. Yeah. The biggest risk factor, and that's aging.

Now we are at early stage in trying to understand how how this works, how do we actually interfere with the aging process. I think we can slow it down. There's some early evidence that we might be able to revert.

Dr. Mark Hyman
Mhmm.

Dr. Eric Verdin
And and I think this is really what animates all of our work, is really the idea that we're going to be getting to the root core of all of these diseases.

Dr. Mark Hyman
Well, that's it. That's how I think is root cause. Like, how do we deal with root causes? That's what functional medicine is, is root cause thinking. And it's just a different way of thinking about things.

And I heard it said that if we cured cancer and heart disease and we just got rid of them completely from the face of the planet, we'd extend life by five to seven years. And if we targeted the underlying mechanisms of aging, we call the hallmarks of aging, we could extend life by thirty or forty years. It's orders of magnitude more.

Dr. Eric Verdin
Totally agree.

Dr. Mark Hyman
Is that

Dr. Eric Verdin
right? Yeah. There seems to be right now, based on what we know, there seems to be a hard stop at a 115, a 120. Very few people have gone one person has gone to the door.

Dr. Mark Hyman
Come off.

Dr. Eric Verdin
But I'm And

Dr. Mark Hyman
she smoked, and she drank, and she need chocolate, but she didn't get married. And and

Dr. Eric Verdin
some some question some have questions, you know, the veracity of whether she was Madame Calm off her her daughter who was collecting Social Security benefits. So that was so there there's been a lot of controversy, but, you know, a handful of people have lived about a 115. There's a hard stop at a 100 around a 115. So imagine that everyone getting there. That that's already and I imagine everybody getting to 95.

That would already be amazing. So, one of the reasons why sometimes as we we we talked about it, I call it grumpy or unimaginative or not ambitious enough as people are feel that I should be projecting bigger numbers in terms of what we're gonna be able to do in the future. And we might, but the bottom line is no one can walk around and tell you, I'm gonna live to a 140, a 150. We don't have any evidence for this, so why even say this?

Dr. Mark Hyman
You mean the don't die thing is not real? No. No. No. I I You're you're not bent on that horse.

Dr. Eric Verdin
I'm not even we're not even talking about immortality because that's a whole other ballgame. Yeah. You know, people talking about immortality say, I I I've I've said on the record, if you're looking for this, join a church. Don't don't come to the longevity field.

Dr. Mark Hyman
Yeah. Exactly.

Dr. Eric Verdin
I I'm really we are focused on on two things. One is what can we do really to push the envelope very far? But, also, what can you do today? Yeah. Because that's really the the most important, Frank, to to modify the way we

Dr. Mark Hyman
This is so important because right now, I mean, there's a lot of cool things happening, like, yeah, Monaco factors and some big money behind researching ways of gene modification or inserting transcription factors that regulate aging and can reverse biologicals. Those are kind of sci fi, and there there's some real money and real research going on, and that might do something. But right now, what you're saying what I hear you saying is we can really look to getting to at least a 100 most people if we do all the things that we need to do, given what we know now. We focus on the fundamental mechanism of aging, what people call the hallmarks of aging, and we're gonna kind of dive into one of them particular today, inflammation, or what we call inflammaging, is that all these are related. They're all interconnected.

They're not really all separate phenomena. They all kind of cross talk, and they influence each other. And there are some meta frameworks that actually allow us to kind of push push the field of those hallmarks into health. Yes. And I think that that's kind of how I think about it.

And all the things that people are listening to and hearing about, whether it's saunas or, you know, peptides or or exercise or whatever whatever the modifications are, NMN or whatever the molecules are, they're all affecting these fundamental systems. And and I think that's that's the kind of the home kind of core message I wanna get today. And and with that framework, I wanna dive into this concept of immune aging. As you look across all the diseases of aging, they're all related to inflammation. Brain aging is inflammation.

Alzheimer's inflammation. Cancer's inflammation. Obesity's inflammation. Diabetes inflammation. Heart disease inflammation.

Yeah.

Dr. Eric Verdin
And we're talking about a common core.

Dr. Mark Hyman
Right. And and and there's a lot of ways to get to inflammation. And when you have inflammation, it affects everything else. It affects your mitochondria and your genes and your telomeres and your microbiome. It's all connected.

Right? So what's the cause and effect sometimes are not always clear, but but the phenomena is really clear.

Dr. Eric Verdin
I can say a word about this one thing that's remarkable about in inflammation. It's a normal response of your body. So, you know, if you cut yourself, if you burn yourself, you're gonna see the appearance of redness first, then there'll be a bubble, and then there's a whole repair process. And you'll see the area where it's been burned, actually, will stay inflamed eventually. So this is this is the what we call acute inflammation, which is a normal response of your body to damage.

Okay? Eventually, that bubble is gonna recede. There'll be a crust. The crust is gonna fall. And soon, there'll be maybe a little redness, and then eventually, everything will be gone.

So that's inflammation at work. Because I think inflammation is a bad name. It's something that's always bad. Inflammation is critical. This is our response to damage to fix it.

The problem of aging is persistent inflammation. So inflammation doesn't go

Dr. Mark Hyman
It's like chronic sterilant.

Dr. Eric Verdin
Yeah. And it stays on. And what's remarkable, it becomes part of the problem. Yeah. So a a body response that was there to actually heal becomes part of the chronic response.

And then so there's a lot of interest in trying to understand how does that what's cause? What's effect, as you mentioned? And how do we actually suppress it and eliminate it? And I think that's key.

Dr. Mark Hyman
And I think, you know, as we as we're younger, immune systems are very vigorous, and they're very good at fighting infections and kind of preventing cancer. As we get older, it's kind of switches a little bit. Like, we don't get so good at fighting cancer or preventing infections. Right? Yeah.

And so I I wanna unpack that a little bit, but what what I wanna sort of create a little bit of a a framework is a new concept that I think people are gonna hear about today, which is the link and the connection between mitochondria and inflammation. They're often thought of as separate. There's like mitochondrial dysfunction is one of the hallmarks, and inflammation and, you know, inflammaging is another one, but they're not really separate. So I I wanna really frame that up as we're talking about this. So let's talk about about this concept of how sort of cellular energy and mitochondrial function and and and inflammation are and immune aging are connected.

Dr. Eric Verdin
Maybe I'll say a word about the the hallmarks of aging first because I think it it will put everything into context. So these hallmarks of aging that you mentioned, mitochondrial function, senescent cells, and all this, was a way to for the field to organize all of our different activities. Everybody was doing research. There was no organization.

Dr. Mark Hyman
Blind man and the elephant.

Dr. Eric Verdin
Exactly. And so people sometimes were working on something similar. They just did not call it the same. So this hallmark of aging review was published by, Guido Krummer and his colleagues and organized these these molecular manifestation of aging. So that's what they are.

If it you know, the paper was published. It created a lot of excitement because we were finally starting to think about a problem in all of its dimensions. Yes. Okay? And so meetings were organized on mitophagy, on senescence, and so on.

What people fail to recognize is that biology is a series of incredibly intricate networks. So there's there's no not such a you can't put these hallmarks in neat little boxes.

Dr. Mark Hyman
That's what I was trying to say. Yeah.

Dr. Eric Verdin
And and so that that the reason I'm bringing this up, because when we think about most people think about mitochondria, they think, oh, mitochondria, that's energy power for the cells. Well Simplistic. It's very simplistic because the mitochondria is also an incredible sensor for what's happening in terms of inflammation. An example that I like, how how does mitochondria connect to inflammation? So if your mitochondria are not functioning well, they generate what we call radical oxygen species.

These are Free radicals? Free radicals. These free radicals are nasty. They will, by themselves, create inflammation.

Dr. Mark Hyman
They're oxidants. They're the

Dr. Eric Verdin
pro oxidants. Exact that's where the whole theory of antioxidant came from.

Dr. Mark Hyman
That was Denim Harman way back when.

Dr. Eric Verdin
Yeah. Exactly. Not recognizing that free free free radicals actually can also be positive.

Dr. Mark Hyman
They They're cell signaling molecules. Exactly. So is inflammation. Everything is like a signal. Right?

Exactly. And it can be too much or too little, and that's what the balance is the key.

Dr. Eric Verdin
Totally. And so having a lot of oxidative stress is not good, and you can tamp it down. You're probably gonna do yourself some good, but you can't block it all because then you run into a whole series of other problems. So that's one way by which if your mitochondria are not functioning well, you're gonna create more oxidative stress. Another way is mitochondria

Dr. Mark Hyman
And oxidative stress leads to inflammation.

Dr. Eric Verdin
Exactly. A direct link. Another way, which is actually fascinating where there's so much work going on right now is you might be aware that mitochondria have their own DNA. Yeah. Okay.

Dr. Mark Hyman
So From your mother.

Dr. Eric Verdin
Yeah. Exactly. Mitochondria are actually descendants of a bacteria Yeah. That was absorbed by by ourselves and formed a whole kingdom called the eukaryotes. And so we have within ourselves these bacteria that have their own little genome, and they replicate and they, you know

Dr. Mark Hyman
And they look like a bacteria.

Dr. Eric Verdin
Yeah. Exactly. They look like a bacteria. Now we have in our cells mechanism that allow us to recognize the presence of DNA in our cytoplasm. Remember, the DNA is normally in the nucleus of the cell.

The only way you can get DNA in your cytoplasm is for two reasons. Either

Dr. Mark Hyman
And so, baby, cytoplasm is like the liquid inside your cell, like the is a the cell is like a baggy. Exactly. Inside the baggy is like your nucleus and the mitochondria, but there's also this squishy liquid, and that's the cytoplasm.

Dr. Eric Verdin
Get Okay. Perfect. Sorry about that. Getting too technical. But all of you

Dr. Mark Hyman
I'll stop you if I I gotta translate. All

Dr. Eric Verdin
all of your DNA is in the nucleus, and it should stay there. So if your cell gets infected by a virus, there's a system in the cytoplasm that will recognize the presence of abnormal DNA.

Dr. Mark Hyman
A viral DNA.

Dr. Eric Verdin
And it will act yeah. Viral DNA. And it will activate an inflammatory response. The same thing if your mitochondria get damaged, they start leaching out their DNA in the cytoplasm. That's also recognized as an inflammatory signal.

So the body does not know. It says, oh, there's something wrong.

Dr. Mark Hyman
It doesn't recognize even your own mitochondria as you. It sees it as a foreign No. Mitochondria.

Dr. Eric Verdin
Yeah. And so and that's that's a there's a whole system called c gas sting. There's new inhibitors that are targeting this that are showing amazing effects. So again, a completely new different direction of research. What are the mechanism by which I'm trying to think?

I think this would be probably the the two major

Dr. Mark Hyman
But also inflammation is is and it it also affects mitochondria, so bidirectional. Right? Yes. Every If there's an inflammatory signal from your microbiome, for example, which is most people have terrible bacteria, that can affect your mitochondria. Absolutely.

An environmental toxin which creates an insult to the my you know, the mitochondria, it's also that can also create inflammation because these are autogens.

Dr. Eric Verdin
Right? When you when you age, for example, you know, your NAD levels decrease. My we've talked about this before together.

Dr. Mark Hyman
You can go back and listen to our old podcast on NAD.

Dr. Eric Verdin
Yes. NAD is critical, for example, for mitochondrial integrity and function. So as you age, these mitochondria become tired. They don't divide as well. They're not cleared as well.

They don't generate as much energy. So there are a whole series of problems that are linked to the aging process that makes it, makes your my mitochondrial a really essential pivot in in all of this. And the immune system is is like any other system. Like your muscle system, you don't have the same strength when you are young, as when you are old, the same thing. Your immune system is performing at a much lower level.

So let's kinda

Dr. Mark Hyman
unpack the immune system starting there. There there's two parts, really. There's the ancient generalized, like, carpet bombing immune system, which is preserved, you know, in many, many species. It's not so smart. It's just like a kind of a kind of a fire bombing city as opposed to our kind of smart targeted bombs.

Yep. And that's called the innate immune system or the ancient immune system. And then there's the adaptive or that's also called the cell mediated immune system, which we learned in medical school, which is mediated by the T cells. And then there's And the B cell. And the B cells.

And then there's the adaptive immunity or the antibody immune system where we create specific target antibodies. For example, against COVID, when we check our COVID test, that's what we're checking as antibodies. Can you kinda unpack what those are, what they do, and how they change as we age?

Dr. Eric Verdin
Great question. So so think about again, two system. Innate, first line of defense.

Dr. Mark Hyman
And I promise everybody, we're gonna get to the the news to use here. I just wanna kinda lay the groundwork here.

Dr. Eric Verdin
Yeah. First line of defense is the innate immune system. It's a think about a country defending itself. It would be the barbed wire at the border, you know, just or or maybe a series of of people who are, you know, arming the border, making sure nobody crosses. The we talked about DNA in the cytoplasm.

That's part of the innate immune response. So there's a whole series of receptors that allow every cell to determine whether something there's a dangerous signal. Yeah. Okay? During aging, for example, we have a a disruption of the gut barrier.

Some of the bacteria in our intestine can leach out into the blood, and they act they cause inflammation. Simply that the disruption of your gut barrier will cause inflammation because some bacterial product are leaching out across again, in the blood. All of your cells see that, and they think there's an infection. And so they activate the first line of repon response. So that's inflammation, by the way, is inflammation is is that innate immune response.

Dr. Mark Hyman
The chronic sterile age related inflammation.

Dr. Eric Verdin
Or acute as well. You have damage. You know, you burn yourself. There's damaged tissue that's recognized by the innate immune system. It starts repairing.

That part of the immune of the immune system as we age becomes hyperresponsive. It just sees problems where there's none, and that's a whole concept that people have talked called inflammaging.

Dr. Mark Hyman
That's what I that's what I was getting at when I said related to the aging.

Dr. Eric Verdin
So that's inflammaging. The second part of the immune system you mentioned is the adaptive, which is totally different. It's actually an educated system. It will learn from what it has been exposed to. So imagine you you get an infection with influenza from with the virus.

The body will learn how to recognize it, and it will develop specific tools, T cells and B cells that will make specific targets. That's the basis for vaccination. When you get a vaccination, you get a little dose of something. The body learns how to recognize it, and it will confer a protective response that will last sometimes a lifetime. So

Dr. Mark Hyman
Yeah. Like a measles vaccine.

Dr. Eric Verdin
Right? Measles vaccines or even infection that you have when you were a kid. Herpes zoster, you can have an infect chicken pox when you when you're a kid. And for many people, you actually have immunity for life. Although, you should get your Shingrix.

Dr. Mark Hyman
Shingrix. I

Dr. Eric Verdin
I hope we can talk about this because this is really fascinating in terms of the implication of some of these vaccinations. And that that system, the the whole immune system that's adaptive depends on in part, from your thymus. Thymus? Yes. Thymus is a gland

Dr. Mark Hyman
that is called sweet breads.

Dr. Eric Verdin
And Exactly.

Dr. Mark Hyman
Some of

Dr. Eric Verdin
us had them the

Dr. Mark Hyman
other night for dinner.

Dr. Eric Verdin
Yes. It's I

Dr. Mark Hyman
think it's gonna help my immune system, but I don't think it works like that.

Dr. Eric Verdin
No. But so that's exactly what it is.

Dr. Mark Hyman
Which shrinks as we get older.

Dr. Eric Verdin
It shrinks as we get older. By the time you reach 50, most of us, it's gone. Now the problem when you do this is you're not able to generate the new cells. So you are living with the number of cells that you had at age 50. And and these cells dwindle slowly over time so that your immunity, your ability to mount a new immune response will decrease.

So that vaccinations are given mostly when you're young, and as you get older, your ability to mount a vaccination response decrease.

Dr. Mark Hyman
You don't respond as well to vaccines.

Dr. Eric Verdin
You don't respond. And for example, if you get an a flu shot, you're gonna get actually a a specific flu shot for elderly older individuals that will try to trigger your immune system more forcefully.

Dr. Mark Hyman
Mhmm.

Dr. Eric Verdin
And so this failure of adaptive immunity as you age is one reason why we saw during COVID nineteen the risk of death increasing so much during age as a function of aging. Yeah. This is why thirty thousand people, I believe, still die from influenza every year. Mhmm. The same thing with RSV.

So there is an epidemic that no one talks about, which is the fact that older individual die from viral and pneumonia. All these infections at much higher frequency than younger ones. So there's a lot of interest in the aging field to try to say, how can we mitigate this? Can we restore the thymus? Can we understand what makes the thymus go away?

And so on. So it's almost like

Dr. Mark Hyman
the worst of two worlds. On one hand, the innate immune system starts to be overactive and more indiscriminate, and creates this low grade chronic sterile inflammation that we call inflammation. And at the same time, our antibody levels are less able to to mount a response their cells that do antibodies are less able to mount a response to invaders. And so we we can't fight cancer. We can't fight infections as well, and so we get all these different problems.

Dr. Eric Verdin
That that's a great point. You you can respond to a vaccine in the same way. As you mentioned, the the immune system the adaptive immune system plays an important role for what we call a tumor surveillance. So it goes around the the tissues and it tries to determine, is a cell acting funny? Is it senescence?

Is it is it a zombie cells? If it's a zombie cells, we'll try to eliminate it. So there are many mechanisms by which the immune system participate in our health. One last point is the fact that these two immune systems do not function independently from one another.

Dr. Mark Hyman
Right.

Dr. Eric Verdin
System is really smart. So the innate immune system, when it's activated, actually provides the help to educate the adaptive immune system. And so if you have a chronically active innate immune system, that doesn't jive well with the adaptive. So the the whole system degrades as as we age.

Dr. Mark Hyman
And so as people are listening, this isn't good news. Right? The immune system ages. You can't mount responses to infections or fight cancer. You get this chronic inflammation that creates a downstream cascade that leads to all these chronic age related diseases, what do we do about it?

How do we how do we manage that? Is there a way to kind of reduce inflammation or to stop the inflammation or to improve immune response? How do we do that given what we know in longevity now? Because immune aging is what we're talking about.

Dr. Eric Verdin
Yes. It's very hard to sort of first thing I I should say also why immune aging is so important. There's evidence that if you induce aging only in the immune system and we can do this in mice. Okay? So you can make a a lesion only in the immune system.

That will induce organismal aging. So it will not just induce aging of the immune system, it will induce secondary aging in the other organs. And so that's and and that's been shown in two different studies. So it's real data in mice creating these artificial tools that we have. We can make only a lesion in the immune systems, which means the the immune system has has a has a dominant role in in our aging.

That has been proven in another way. You might have heard about the new clocks that Tony Whiskoray has generated, these organ specific Yeah. Proteomics clock. Okay. So you can Is

Dr. Mark Hyman
that Generation Labs? It's Vero. Vero. Vero Labs. Yeah.

Yeah.

Dr. Eric Verdin
Yeah. That's right. So what what this company and and Tony's work have shown is that they now can draw from from a a blood draw, they can measure a series of proteins that are circulating that are reflect reflective of the activity and the health of all organs. So they can determine

Dr. Mark Hyman
Like, your organ clock, how old your brain is, old your heart, your kidneys.

Dr. Eric Verdin
Right? Because, obviously, you know, you can be in an incredible health in your whole organism. If your brain health is twenty years ahead, you're going to be not doing so well. So there's always that sort of rate limiting organ that could be causing all of the problems. So we want not to age at an accelerated rate in any organs.

But what his data, they've gone back and analyzed 50,000 people from UK Biobank, huge dataset from from England. And they found that there are two organs that are predictive of your demise, in terms of your lifespan. It's the immune system, and it's the brain. And it's not that surprising because they are the two organs that are distributed.

Dr. Mark Hyman
They're the sensory organs.

Dr. Eric Verdin
Yeah. And and your brain, you know, your brain has ramification in the whole organism. Your nerves your brain does not just sit in in the cranium. It sends, you know, nerves to the whole body for muscle, but also to your organs and so on. So same for the immune system.

It's not only sitting in your lymph nodes. It's in your skin. It's in your liver. It's in your gut. It's absolutely half of your immune system is actually in your gut.

So that means that all of this data in aggregates mean that maintaining immune health is really critical. And it's gonna be one of these, you know we used to think as physicians that the critical organ for survival was your heart because half of the population was dying of heart attack, and and we still have that problem. But beyond this, let's say we can cure heart attacks, as I think we will in the few in the near future.

Dr. Mark Hyman
But also that's related to inflammation.

Dr. Eric Verdin
Yes. But we that's also so maintaining immune health is going to be really critical. Well, the you make

Dr. Mark Hyman
an interesting point because I the way I think about the brain and the immune system is there the brain is is the sensory organ for macroscopic things. Yep. So it's they're kind of mirrors.

Dr. Eric Verdin
They're very, very important in maintaining tissue integrity and so on. So what do you

Dr. Mark Hyman
do for helping your immune system age well? Doctor. Merton.

Dr. Eric Verdin
That's a tough one. So I think

Dr. Mark Hyman
Or at least better phrase, what do you think the science best says we should do?

Dr. Eric Verdin
Yes. First, we have to mitigate inflammation. Okay? Because I think as we we've talked about inflammation is not only a response, it becomes a driver. Yeah.

And there are lots of sort of self amplifying loops that happen there. If your immune system becomes activated, it can actually induce that. It can try to repair, but eventually, it can actually cause damage.

Dr. Mark Hyman
The solution becomes the problem.

Dr. Eric Verdin
The solution becomes the problem. And so mitigating this inflammation is key. And one area, for example, that I think there there are multiple areas that we can talk about. Gut health, I think, is critical in this respect for me. And I tell people this is something that not enough people are talking about in the longevity field.

You know? And, actually, the people who are talking about it, I think, focus on a lot of the wrong things. A lot of focus on probiotics, and I think we should be focusing on prebiotics and postbiotics. And I'm happy to so I'm I wanna get

Dr. Mark Hyman
into that. That's a topic we're we're gonna get to. Great one for

Dr. Eric Verdin
me, and one that I I think we're not talking about enough.

Dr. Mark Hyman
And if you ask most doctors, how do you create a healthy gut? They have no idea. Yes. And there's a way to do it. I mean, that's what functional medicine my my my the joke about me where where at my old job at Canyon Ranch was I was a doctor to see every poop.

Because I wanted to look at every stool test, look at every microbiome, see what's going on, reset the gut as a way of treating all these kinds of diseases.

Dr. Eric Verdin
Agree. Totally agree. And I I think for most people, like, totally unaware. And, you know, the only thing they think about this is when you walk into a Whole Food, there's a fridge full of probiotics that I said, I wouldn't go near those if I were you because we don't we except maybe for achimansia. Yeah.

Most of those, we don't know how to use them. Or maybe lactobacillus.

Dr. Mark Hyman
And your diet is what creates your microbiome for the Exactly. For the main the main reason. You'd focusing on prebiotics. These are foods, whether

Dr. Eric Verdin
it's Yeah.

Dr. Mark Hyman
Asparagus or art juice from artichokes or plantains. So these are these are things we can eat that actually feed the good bugs.

Dr. Eric Verdin
Agree. Or if you're not able and actually, the evidence points to the fact that most of so prebiotics would be all fiber. And most of us actually have an inadequate intake in our modern way of eating of of fiber. Yeah. And so I tell people, you know, if you have to supplement, supplement.

But there there are a growing number of good supplements that you

Dr. Mark Hyman
can take. Minnesota, when you look at the historical fiber intake of hunter gatherers, it was, like, estimated to be a 150 grams of fiber a day. We ate at 15. And the average American is Exactly. You should be trying to get to 35, forty, fifty at least.

Dr. Eric Verdin
You know? My wife is from Germany, and I I suspect you've traveled there when you eat a slice of bread from Germany.

Dr. Mark Hyman
Yeah. You need a meat slicer. I I visited a friend of mine in Germany when I was, like, 20, and and she had a one of those, like, deli meat slices in her kitchen. Like, what is this for? She's like, for cutting the bread.

Yeah. As it does a knife doesn't work.

Dr. Eric Verdin
Yes. Yeah. It's dense. And that bread is you know? But the the other way is this bread also will force you to

Dr. Mark Hyman
chew Do.

Dr. Eric Verdin
And will get you a large jaw, which will stop sleep apnea. So, you know, there's there's a lot of interesting things in terms of the the fact that our diet has become almost like semi liquid Yeah. Creates all of these problems in terms of facial features and and so on. So

Dr. Mark Hyman
That was the work of that dentist who went around I forget his name right now, the the guy who went around and saw all the indigenous cultures and looked at all the teeth and the jaws. I mean, you know, I I was in Africa, and I saw the gorillas, and I got to go to the museum, and I got to see all the gorilla skulls. Perfect teeth. Like, they had perfect teeth. They don't need dentures.

They don't need, you know, they don't need braces. I mean, it was amazing to see. And I was like, wait. That their diet is what's driving their dentition, and their dentition is driving their health.

Dr. Eric Verdin
Absolutely. I'm reading James Nestor's book, Breathe. Yeah. Oh, Breath. I don't know.

And that there's a whole chapter on this. There's this sort of adventurer who was one of the first one to actually, visit, American, native Indians.

Dr. Mark Hyman
Yeah. Yeah.

Dr. Eric Verdin
And what was one of the things that struck him the most is how the teeth of all of these native Indians were absolutely perfect. No crooked. They didn't have to remove wisdom teeth. They didn't have to do anything. So that's a fascinating aspect of it.

But I think the two are linked. So this idea that we're eating a semi liquid diet, soft bread, soft everything versus chewing hard has implication not only in terms of our microbiome, but also our our tooth structure, our ability to breathe through our

Dr. Mark Hyman
nose, and so on. Whole foods, fiber

Dr. Eric Verdin
is the root everything.

Dr. Mark Hyman
Yeah. So phytochemicals, fiber, whole foods, getting rid of processed food, sugar, all that's gonna be the biggest lever for inflammation, stress, sleep, removing toxins. These are the things that I think about. Do you think about those? Is there anything else?

Dr. Eric Verdin
Is this is the foundation. And I think, you know, I

Dr. Mark Hyman
Sleep, stress, exercise, food, toxins, microbiome. Human connection. Human connection. Yeah.

Dr. Eric Verdin
All all of those is for me the foundation of longevity medicine. Yeah. And, you know, it's people people have argued, well, this is not sexy. This is not what people want. They want they want supplements.

They want drugs. They want a shortcut. And I I'm I'm all for shortcuts, but I believe it just doesn't work.

Dr. Mark Hyman
Yeah.

Dr. Eric Verdin
And and we and also, plus, none of these shortcuts have been proven. The rest of everything else has been proven, the effect of physical activity and so on. So the stance that I've taken lately sort of in social media and and talking is is one that is a bit contrarian to what some my colleagues are advancing in the longevity field. I'm as excited by as anybody by what we're gonna be doing twenty years from now. But let's not forget where the foundation is, and we can create so many problems that are so easily solvable as a society.

Not everything needs a pill. Yeah. One of the most

Dr. Mark Hyman
interesting studies I ever saw was it was a whole field of sociogenomics, which I kinda came up with on the term myself because I I kinda saw Paul Farmer's work in Haiti and how he helped people and using community work health workers to help. And I just I just came up with this concept, and then I started researching it. And I was like, wait. There's a whole literature on how our social connections affect our immune system. And then if you're in a loving, connected relationship or in an interaction, it's going to reduce inflammation.

But if you're in a conflictual, literally inflamed relationship, it's going to create inflammation, which I

Dr. Eric Verdin
I love that whole aspect.

Dr. Mark Hyman
Yeah. It's really interesting. And it's More cuddle puddles.

Dr. Eric Verdin
Yes. Incredibly frustrating for me that we know from from the happiness studies, for example, that the the biggest factor determining your longevity is your social social connections. Yeah. Number of loving relationship you have, your sense of purpose. The problem is that these are also the hardest one to study, especially in animal models.

I can go ask a mouse what what its sense of purpose is, you know, living in a little plastic box and and eating the same food that looks totally disgusting. So there is, you know, we've been talking actually at the back about creating a center for a psychobiology of aging, which would really try to because at the end, everything is driven by molecular mechanism. I mean, we are biochemical feature.

Dr. Mark Hyman
Could you reproduce, like, a whole natural mouse environment? You know? Yes. Like, they're

Dr. Eric Verdin
People are doing this.

Dr. Mark Hyman
Yeah. It's of interesting. Like a cage. Like

Dr. Eric Verdin
They're creating these, like, really and, you know, we study longevity, by the way, in these mice that live like, you know, these prisoners.

Dr. Mark Hyman
I mean,

Dr. Eric Verdin
they they're alone in their cage. There's no distraction. There's nothing to do. The food is there all the time. It doesn't taste good.

Imagine I mean, the mice, I'm sure, have the same needs that we do in terms of having a diversified environment and so on. So there's a whole group of people thinking that we should create these. And maybe, you know, the drugs that we find that work in mice would be a lot more relevant to what we have to do in you.

Dr. Mark Hyman
Amazing. Alright. This is so good. So I think we we kinda got a good dive on the immune system. Let's kinda switch over to mitochondria.

Yeah. And help help us understand the the how mitochondria and cellular energy are so central to aging. Because to me, they're kind of like the final common pathway that that goes wrong, and inflammation is causing them to malfunction. And how do we how do we understand how how that's occurring and why and what we can do about it?

Dr. Eric Verdin
Yes. So where do we start?

Dr. Mark Hyman
Let's start with, like, why why are mitochondria and cellular energy so important to aging?

Dr. Eric Verdin
The big reason that everyone knows is the most people agree on is the energy energy requirement. So everything that we do is dependent on energy. What people think about moving your arms, thinking. Everything that we do is depending on generating energy. Typically, we get that energy from our food.

Okay? So we're able to extract energy from the food. The place where that energy conversion happens is in the mitochondria. Okay? Most of your our energy generation happens in the mitochondria.

We also know that as we a so all of these activities, thinking, moving are the two major ones. But there's a whole other aspect of energy that most people do not appreciate is that repair. So we are constantly subjected to toxic insults. Yeah. Okay?

We talked about the free radicals that would induce damage. Damage in our proteins, damage in our DNA, damage into our membranes. All of these lesions, these damage have to be repaired. So we have in ourselves little monitoring mechanism that constantly look at everything to make sure everything is fixed. As soon as a

Dr. Mark Hyman
Like sensors.

Dr. Eric Verdin
Sensors. As soon as something is seen to be damaged, a whole crew is sent to repair it and fix it. For example, I'll give you an example of DNA damage. Your DNA is the the code that encodes every one of our cell. It it sends the reason that if you're making a a a a damage and you're creating a mutation, you have the potential to change the code.

And, essentially so if you allow this to happen all the time, eventually, the whole system is gonna go awry. So there are human mutants who are people who carry a mutation when from their parents that where they are not able to repair DNA damage. They typically live until 20.

Dr. Mark Hyman
You're the progeria patients?

Dr. Eric Verdin
Yeah. Some of these progerias. So there's a whole series of syndromes, xenoderma pigmentosum, ataxia telangiectasia, a whole series of these DNA damage repair, all really tough disease to live with with many of them with very shortened lifespan. So that that highlights how important all of these repair pathways. We also have, systems to repair unfolded proteins.

Remember, proteins is a string of amino acid. It has to be folded in extremely precise manner to function. If it becomes a little unfolded, all of a sudden, it's creating problems.

Dr. Mark Hyman
And that's one the hallmarks of aging is protein damage.

Dr. Eric Verdin
Yes. Protein proteostasis, the idea of maintaining all of your protein in good shape. Again, there's a whole series of enzymes that we call chaperones that are sent. If something is unfolded, they're sent, but all of this refolding takes energy. And so our body always makes this calculus.

Okay. What do I repair? What do I not repair? And so we try to repair as much as we can, but there's an energy cost to this. Okay?

So you also have to move. You know? So the the the the the the difficulty for a living organism is how much energy do I allocate to repairing everything perfectly, or what can I live with and still move, still hunt, still, procreate, still so this antagonist between repair and reproduction is really at the root of aging? And, so as we age, the mechanism of production of this energy starts become limiting. We mentioned these bacteria are are these mitochondria become

Dr. Mark Hyman
old. But there's a way to repair them and renew them. Right?

Dr. Eric Verdin
That's the key. So there's actually a special repair system just to get rid of old mitochondria that are damaged. It's called mitophagy.

Dr. Mark Hyman
Yeah. It's like autophagy, but but for your mitochondria. Autophagy is where you kind of eat yourself and clean yourself up. And

Dr. Eric Verdin
autophagy is activated when you're resting and actually allows you at night to actually repair a lot of the damage. And what's what's amazing about autophagy is that it's a self eating mechanism that's tar specifically targets what's been damaged.

Dr. Mark Hyman
Right.

Dr. Eric Verdin
So imagine, you're not eating, so you still need energy. Yeah. And that energy now has to come from the inside. Your system has a mechanism that goes to clean up the attic first. Right.

It doesn't destroy the kitchen. Right. It goes into the attic and say, okay. What's all the garbage here that I can I can still, you know, resell and make a profit without actually touching the kitchen? So, and mitophagy is an arm of this that selectively targets defective mitochondria because they are so central.

But like everything during aging so what is aging? The progressive accumulation of damage. Even though we have all of these repair mechanism, we don't repair perfectly. Yeah. We've repaired pretty good.

During our twenties, the rate of repair is such that if we were to continue repairing at the same rate, we would lift to a thousand years old. So during our twenties, we're actually doing incredibly well. The problem is as a little damage accumulates over time, eventually, of the damage might actually target the repair mechanism. And we know aging is not a linear process. It accelerates.

Yeah. The older you get, the faster your aging process.

Dr. Mark Hyman
Yeah.

Dr. Eric Verdin
And so the whole idea of activating, reactivating my because eventually as you get old, mytophagy becomes limiting as well. It doesn't function as well. So Clean up system.

Dr. Mark Hyman
The garbage men get old. Exactly. That's right. When I think about about this, it's it's it's such an important kind of framework to think about the the sort of energy of the cell because it really runs everything. Yeah.

And and we kinda do know that everything that impacts aging also impacts the mitochondria and vice versa. And and what there are levers, though, to really take care of your mitochondria. Yes. We talked about NAD on our last podcast, but there's other compounds that induce mitophagy, and that are when we mentioned postbiotics earlier, which are essentially compounds that you eat from food, they get metabolized by your bacteria, and they produce downstream molecules that have function in the body, which I think is a miracle. Just when you think conceptually about it, that you eat stuff, and then it creates like a literally a medicine that turns on different signaling systems in your body to help you repair, renew.

And I and I think from my perspective, and I it sounds like you think the same way. When I think about aging, I think, you know, the body has these innate systems of repair, renewal, regeneration. We just burden them, and we don't take care of them. Yes. And that's why we age faster.

And instead of focusing on treating disease, if we focus more on our regenerative renewal and repair systems, we do a lot better. And so the way in is through some of these food molecules. And I I I I call I I have this joke. I call it a symbiotic phyto adaptation. We symbolically evolve with plants and use their compounds to regulate our biology and because we're lazy.

Like, we don't make vitamin c, so we get vitamin c from food. We don't make, for example, one of these postbiotics called urolithin a, so we make it from pomegranate or other elliotannins that are in, you know, walnuts or berries or whatever. So help us understand how for example, this molecule, urothenate, which you published on. It's Yeah. And we'll link to the papers in the show notes, and which I, by way, take every day, because the literature is impressive on it.

What does it do, and why why is it getting so much attention now? And we've learned about it more in the context of exercise, improving, you know, exercise capacity, v o two max, and fitness, and muscle health, and mitochondrial health. But it it does have a linked immune system. So what is it, and how is it linked to these things that we just talked about? So I'm wrapping back up with immune function, the gut, and mitochondria, because it's like one thing.

It's a it's

Dr. Eric Verdin
a it's a really cool story because it's one really I I would call it as sort of a human in in general, really. And so in some way, we've known for a long time that, pomegranate juice is actually healthy for people. And there's a whole you know, there there have been studies showing that consumption of pomegranate juice is actually confer some health benefits. What was not clear is what the mechanism so some scientists a good friend of mine, Johan Auerks, who works in Lausanne, actually went and looked for what is in pomegranate juice, and they found these ellogitannins, these compounds. What they also realized is that these compounds are not acting by themselves.

They are actually metabolized by your microbiome. And that's really and the the product of that is made by by your microbiome is is called urolithin a. Okay. Now what's the catch is only about thirty five to 40% of people's microbiome because remember, all of our microbiomes are different. And some 60% of people's microbiome is not able to make that conversion.

Dr. Mark Hyman
So we trash them because of our diet, because of antibiotics, because of, you know, toxins, all this stuff.

Dr. Eric Verdin
So we kinda Having a a rich you know, most of us have more than a thousand different species of bacteria in our guts. And the problem the the the the the the complicating factor is most of us have different species. So you cannot compare your microbiome and mine even though might both be very healthy.

Dr. Mark Hyman
They can change. Like, I've seen the study that you you have people on a vegan diet or feel a meat, paleo diet. They their their microbiomes living in the same personal change.

Dr. Eric Verdin
Right? We don't know how to read it well, but we know certainly what upstream, factors can actually yield a a really complex and rich microbiome. Yeah. So this is a clear example of where sort of human ingenuity has been able to identify a single molecule, urolithin a, that is the result of a input from a a food product Right. From my from a plant, from my granite juice, it gets transformed by a fraction of us into a product that has immense benefits.

So company was founded based on this. I'm a scientist that actually sells this product and, has we've we've been working with them. I say I mean, full disclosure, I sit on the board of that company as a scientific adviser. But I always tell people, I I don't sit on on on the board of supplement company if I don't believe in the science Right. And if they're not willing to actually conduct clinical trials.

And it's one one thing I think is commendable for Amazanthist that have been going through clinical trials one one at a time Yeah. To actually document and prove the efficacy of what

Dr. Mark Hyman
I agree. And they're a sponsor of the podcast, and that's why also I I don't let everybody sponsor my podcast. You mentioned all of you last week because I think I want stuff that I know has has legitimate science behind it, and, you know, this published in major journals like New England Journal or Jim or others sell. Yeah. So So I think I think this is important.

Dr. Eric Verdin
So to me, you know, the I'm not opposed to to supplements, but we have to apply to them the same kind of standards that we've applied to generating all of the drugs that we we have, and that that's how medicine has moved forward. So that being said, you know, we've worked with them on a couple of studies. We still have another study going on with them. So urolithin a has this remarkable, like, ability to activate mitophagy. And mitophagy is not sort of the, you know, as the term implies, it's eating mitochondria, but it doesn't eat them discriminately.

It eats the old defective mitochondria, which is absolutely remarkable. So when you do this, actually, one of the study that we've done was looking at the human immune system of all the people on urolithin a. And what we found is, really actually significant effect even within, one month of administration of urolithin a. We saw some re I would say, what anybody would call a rejuvenation of the immune system.

Dr. Mark Hyman
Yeah. I mean, I I think, you know, early on when I looked at the data, this is years ago, I got excited about it. I saw like a reduction in CRP, which is a very crude marker of inflammation. And we measure with function help, but there's there's even better markers. But how one of the things that you looked at that that indicated that it it helped to reduce the inflammation process?

Dr. Eric Verdin
Yeah. Actually, in our in our case, we we well, some cytokines. We measured the the presence of different cytokines, TNF alpha, I l six, I l one. I And don't remember exactly which ones were changed, but some of them

Dr. Mark Hyman
were And cytokines are the mess messenger molecules of the immune system.

Dr. Eric Verdin
Exactly. And the I l one, I l six, TNF alpha are pro inflammatory molecules. So the higher the level, you know, the higher the inflammation. What we are we focused on in my lab and and with our core at the back was on looking at the adaptive immune system. And and what we saw was actually quite interesting.

We saw an increase in naive T cells. So these are the precursors that are really critical at generating an adaptive immune response. We saw a whole series of other changes in

Dr. Mark Hyman
And just in English, naive T cells are kind of cells that haven't made antibodies yet. They haven't kinda

Dr. Eric Verdin
They haven't made yeah. They haven't been activated to To develop antibody. The T cells. And the the the the B cells would be making the antibodies. So these are the T cells.

Dr. Mark Hyman
That that eat they they cause the B cells to make the antibody.

Dr. Eric Verdin
They help, but they also, by themselves, can generate what we call cytotoxic T cells, c d eight T cells, which are the other so the arm the the innate immune system the adaptive immune system has two arms, T cells and B cells. Yeah. The T cells are making actually, they can kill bad cells. The the b cells can actually secrete the antibodies Yeah. Which help in in the immune response.

Dr. Mark Hyman
And so the urolithin a works on Eight. The the T cells.

Dr. Eric Verdin
It worked on the T cells and actually increased the the the ability of these T cells to recognize their targets. Now this has implication not only for the person who's taking this, but think about you might have heard about the CAR T cells that are used now for cancer cells Yeah. Where we we can extract T cells from a patient and educate them to selectively kill tumor cells. And the problem is that as you get older, your ability to make to reeducate these T cells goes down. And so this would have even implication for cancer.

Yeah. Because they did it in vitro and show that these CAR T cells were actually more effective.

Dr. Mark Hyman
So it makes immunotherapy work better Exactly. If you Yes. Improve and rejuvenate your T cells Totally. Before you start to sort of target them for cancer. That's amazing.

So how does your own thing affect, like, the in the the whole process of longevity? The muscle, the the the inflammation? Like, what do we know about it?

Dr. Eric Verdin
Mitochondria are not just present in the immune system. They're present in every cell. And so think about the the the concept Except

Dr. Mark Hyman
for red cells.

Dr. Eric Verdin
Except for red cells. Exactly. The yeah. They don't have a nucleus. They don't have mitochond I I think they have mitochondria.

Oh, they do? When when you think about mitochondrial function, it's not restricted to the immune system. It's pretty much every cell that has to balance repair and and and dividing and moving forward. So when we, when we think about urolithin effect, they're gonna be pretty much across the whole organism. And, I mean, we focus so far on the muscle where we could see increased endurance, in in people actually on on, humans on urethane a.

We've seen increased immune responsiveness. I my prediction is that when we start looking in the brain, we might see increased performance, increased memory, and so on. Not been proven yet, but, you know, this is a molecule that's not just targeting the immune system or an organ.

Dr. Mark Hyman
You call it pleiotropic. Like

Dr. Eric Verdin
It's pleiotropic, and I think my prediction, I don't think this has been shown yet, but, you can imagine that it would have real antiaging effect.

Dr. Mark Hyman
Yeah. I mean, I think this is interesting because we are looking, like, drugs are affect a single target. They're a single molecule, a single receptor, a single target. You know, when you look at, you know, these longevity interventions, they they have diverse effects across all these different systems. So a compound like urolithin a has many different effects across across the system.

Dr. Eric Verdin
That that's an important point, and it goes back to this whole idea of what we talked about neuroscience. What what does neuroscience really mean when we talk about aging being at the root of everything?

Dr. Mark Hyman
Like geriatrics, gerontology.

Dr. Eric Verdin
That's what that Yeah. That's that's the the The root the root of it.

Dr. Mark Hyman
Yeah. Yeah. But it's the root of it. That's what that means.

Dr. Eric Verdin
There's another example because these, you know, the way we practice medicine is based on a model that dates back to the seventeenth century when we discovered organs. You know, you go see a heart doctor. You go see a neurologist. There's a National Institutes of Health, which has a National Heart, Blood, and Lung Institute.

Dr. Mark Hyman
The National Institute of Organs.

Dr. Eric Verdin
Exactly. So first, I mean, it's a National Institute. It's not a National Institute of Health, a National Institute of Disease. And second, it's based on a seventeenth century model. Now when we talk about urolithin a, it's not that it's going to help your immune system.

It it's going to help everything. Same thing think about rapamycin, which is another darling from the longevity field. No. Its target's called TOR. Target of rapamycin is not only in the immune system.

It's in your brain. It's in your muscles. So when you give rapamycin to someone, you're not affecting just the immune system. You're affecting pretty much the whole organism. And that's that's the the shift that longevity medicine is is doing from sort of organ based reactive model to a sort of system based product.

Dr. Mark Hyman
Yeah. You treat the system, not the symptoms or the diseases. That that's this is actually what functional medicine is. It's it's what we've been I've been doing for thirty years. And it it actually works really amazingly well.

You don't you really get to the root cause like you were talking about the the root, not the branches and the leaves, and that's even the the paradigm we use to describe what functional medicine is. We treat the root and the and the trunk, not the leaves and the branches.

Dr. Eric Verdin
As a physician, I've I've been a fan of this approach of medicine. I think what longevity has done is to add a little bit of a of a more exciting aspect, frankly. And I think I I my my my hope is that it's this is a reintroduction of many of the concept of functional medicine Really? Through the eye of longevity. And I for some reason, it's resonating more with people.

It's become kind of you know, longevity has become sort of a buzzword Yeah. Which scares me also to some degree, but I think it's a it's a wave that we should ride because it will, in the in the end, change, the care for patients and make it much better.

Dr. Mark Hyman
Agree. And I think, you know, the way I think about functional medicine is is a heuristic. It's just a it's just a tool that we use to think about things. It's not the thing itself. Because we trying to describe the human body is infinitely complex, but we're trying to organize it just like we organize the hallmarks of aging.

But when you look at the the functional systems that we describe in in functional medicine, they almost map perfectly across the hallmarks of aging. Mitochondria, immune microbiome, you know, nutrient sensing, all these things are all part of this. And so we may improve that model and get become smarter and smarter, especially as we start to dive into the complex biology that we we barely have scratched the surface of with proteomics and transcriptomics and metabolomics and the microbiomics and the whole that's like you know, at Functional Health, we do, like, a 160 biomarkers at first flush, there's more you can add on. But there's literally thousands and tens of thousands of genes and, you know, millions of variations in your genetics. And there's tens of thousands of proteins, and there's, you know, thousands of metabolites.

And it's it's almost, like, incomprehensible. But now with with big data science and with AI, we can start to make sense of this.

Dr. Eric Verdin
I I could not agree more. And I think this is

Dr. Mark Hyman
because, no, I'm not how smart you and I are. We're never gonna understand that all.

Dr. Eric Verdin
No. And I you know, we we generating data right now in patients at a rate that is beyond anybody's comprehension. And I I'm always comparing, you know, the state of medicine today. And I'm a physician, so this is not a condemnation of medicine. This is just recognizing what it's doing.

You go see your doctor, and you have maybe twenty twenty measurements or your typical annual visit, 20 or 30 measurements. And that's what most people will rely on. Their hemoglobin a one c, their, you know, LDL, not even APOB, their their fasting blood sugar, maybe their a one c, and so on. You're lucky if you get

Dr. Mark Hyman
an a one c. Yes. You're not diabetic. Yes.

Dr. Eric Verdin
And so and a stethoscope, you know, and a little bit sort of something that we

Dr. Mark Hyman
used Seventeenth century medicine.

Dr. Eric Verdin
Something that we used to do, you know, fifty years ago when we were being trained. Yeah. Today, I mean, we can generate out of a single blood draw hundreds of thousands of different data points. And I think a lot of the work that we're doing at the back right now is trying to integrate all of this data because we're generating it

Dr. Mark Hyman
It's right.

Dr. Eric Verdin
AI. And and really

Dr. Mark Hyman
Making sense of it.

Dr. Eric Verdin
Yeah. Making sense of it. So this is these are early days, but I I cannot help to be incredibly optimistic of of the fact that we in in ten to twenty years, we will do we're starting, you know, starting with function health, others in different ways, really to generate a lot more data Yeah. For our patients.

Dr. Mark Hyman
We've got, like, 80,000,000 biomarkers we've tested in the first few years, and we're just getting started. Yeah. And and, you know, I remember sitting on a panel at Cleveland Clinic with Stan Hazen, who's who's a cardiologist who studied the microbiome and its effect on heart disease. And I said, Stan, how many of the metabolites in your blood do you think come from the microbiome? And he's like, I think probably a third, which blew my mind.

I don't know if it's true or not, but you know, when you think about that, it's like our microbiome, like you said earlier, is in a completely neglected area of medicine. You know? Gastroenterologists don't even pay attention to it.

Dr. Eric Verdin
Well, I'll I'll tell you another another day piece of data which I I I keep reminding myself of is half of your immune system. So your immune system is is is distributed across the whole body, but half of it is in the

Dr. Mark Hyman
the Yeah. System. Yeah. Why? Because it's where you're interfacing with the outside world.

Right. You're basically one

Dr. Eric Verdin
cell bacteria.

Dr. Mark Hyman
You're one cell away a sewer. So on the other side of your intestinal lining, which is one cell thick, you know, is on the inside is like a sewer, and on the other side is your bloodstream and your immune system to kinda help take care of

Dr. Eric Verdin
you. So So imagine now what you put in in terms of free fibers, in terms of your food, and all of this has a direct impact not only on the bacteria, your microbiome. I think about the microbiome as an organ, frank frankly. This is an organ, an additional organ in terms of weight. It's pounds.

Dr. Mark Hyman
Metallic Three to five pounds.

Dr. Eric Verdin
People don't realize these are pounds. This is a big Pounds of poop. Pounds of poop. And and all of these bacteria are digesting your food. Many many cases, they predigest what you've eaten.

They're generating all of these secondary products. All of these products go into, into the wall of the intestine, and they educate your immune system. So they this interface there is really, I would say, one of the still big black box of what

Dr. Mark Hyman
It's interesting. And in functional medicine, we've been testing organic acids for years, and part of the things that would show up in your urine are metabolites of things that are happening in your gut. So we can tell if there's yeast overgrowth, if there's bad bacteria, if there's Yes. Things that are going on. It's quite interesting, and we treat people based on that.

It's Agreed. It's pretty cool stuff. Yes. I mean, Eric, this is such a great conversation. I I actually wanna talk to you more.

I'm not gonna do a three hour podcast with you this time. We're gonna break it up. I I wanna talk about some of your new research going forward. I think we're gonna we're gonna maybe do another podcast on this because it's a whole topic in of itself, which is how do we measure biological age? And I'm just gonna set the stage, and I want people to come back and listen to the next podcast.

But we we are trying to figure out, when we say we, the scientific community, trying to figure out, is there a metric we can use to look at interventions to see if it's working? Like, if you say, oh, this molecule or this exercise or this thing, if we do it, will you reverse your biological age? And there's a lot of clocks out there. A lot of people are doing this. We we use one in function, which is based on Morgan Levine's sort of calculation and biological age.

And and it's, you know, it's it's an approximation. And I I say, you know, if you you do the same clock over and over, you're gonna get the same kind of variation, but but they all widely differ. One clock, you were 29. One, you're sixty eight nine. It's like same big guy's seat.

I'm like, man, I don't like the one that says I'm 70. I like the one that says I'm 39. You know? But but you you've kind of done some more research on this. I'm just gonna set the stage of of looking at the clock that has to do with your naive T cells.

Yeah. And and this seems to be more of stable clock that you can kinda track. It doesn't vary so much. So we're gonna come back and do a podcast on that. Okay.

I'm super excited about it. We're gonna put a a link to the show notes. We can

Dr. Eric Verdin
do a full show on clocks.

Dr. Mark Hyman
Yeah. I think I

Dr. Eric Verdin
wanna do a quick shot. I think is really I can say one more thing about these clocks, why is that important? As we move from this reactive to proactive medicine, you know, the way we most people live their life is they they have their lifestyle. Their spouse or their children might tell them, you know, let's try to do this and exercise more. Everybody's living their life flying, what I call flying blind.

Dr. Mark Hyman
Mhmm.

Dr. Eric Verdin
You have your doctor's visit annually. You might get a few a few sample. But eventually, you know, you get into your fifties, your sixties. If you're lucky and you've done the right thing, you're gonna go right through. If not, you get a heart attack.

Yeah. And so the question, that this whole new reinvention of medicine, functional medicine, longevity medicine is re occupying itself is this. Can we accompany you starting at age 20? Yeah. 25.

Measure you every no. Maybe every day Yeah. Using wearables Yeah. Using blood sampling. You know, the technology is going so quickly.

I don't know how we're gonna be doing this. The idea for me is really this constant monitoring. Yeah. Nobody would fly a plane blind today. We have incredible but but we fly our

Dr. Mark Hyman
health medicine is just doesn't make sense.

Dr. Eric Verdin
We fly our health blind. Yeah. And we go to the doctor. We're nervous. Our blood pressure is too high.

We go home. Maybe it's too low. We don't so this whole idea of everyday measurement, hopefully, a way that's totally invisible to you Yeah. Is the future. And so these clocks represent sort of the integration of many of these variables that are gonna tell you you're flying not completely blind.

Yeah. It looks at age 30 that you're on your way to getting a heart attack at age. We can do this now. Yeah. Fifteen years in advance, we can identify the first signature of of disease and and then correct.

So we don't hit the mountain with our plane. We actually correct, and we go a little higher. We go a little to the left or to the right. That's really the way medicine is going to change. And I I think the clock for for for me at this point are an incredibly promising direction.

Dr. Mark Hyman
Yeah. It's true. And I think you're what you're saying is right. I mean, with episodic care, waiting till you have something doesn't make any sense. And I think that's really our mission to function health is to actually help people to create a longitudinal data set with continuous measurements or more frequent measurements, continuous through wearables, for example, whether it's, you know, a ring or a watch or something or or a band or even continuous glucose monitors, and there's gonna be more monitoring like that.

Plus regular blood testing and scanning allows you to create a comprehensive picture and actually detect signals early, these early warning signs decades before you ever see a problem. And I think that's what's exciting to me for every every aspect of aging and every chronic disease. And we're we're getting there, whether it's cancer, heart disease, Alzheimer's, diabetes, we we can see it coming a mile away. And that's that's, you know, what I what I get excited about.

Dr. Eric Verdin
Yeah. Same same for me.

Dr. Mark Hyman
So thanks so much, Eric. Thanks for

Dr. Eric Verdin
doing

Dr. Mark Hyman
your work, and great to see you again. And we'll have you back soon.

Dr. Eric Verdin
Likewise. Okay. Thank you.

Dr. Mark Hyman
If you love that last video, you're gonna love the next one. Check it out here.