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

20:46The only way you can get DNA in your cytoplasm is for two reasons.

20:50Dr. Mark Hyman:And so, baby, your cytoplasm is like the liquid inside your cell. Like the cell is like a baggie. Exactly. And inside the baggie is like your nucleus and the mitochondria. But there's also this squishy liquid, and that's the cytoplasm. Yeah. Perfect. I'm sorry for getting too technical. I'll stop you if I kind of translate. 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. Viral DNA. 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.

21:32That's also recognized as an inflammatory signal. So the body does not know. It says, oh, there's something wrong.

21:38Dr. Mark Hyman:It doesn't recognize even your own mitochondria as you. It sees it as a foreign mitochondria. Yeah. And so 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 direction of research. What other mechanism by which I'm trying to think? I think this would be probably the two major ones. But also inflammation also affects mitochondria. So it's bidirectional, right? If there's an inflammatory signal from your microbiome, for example, which is most people have terrible bacteria, that can affect your mitochondria.

22:15Dr. Mark Hyman:Or if there's an environmental toxin which creates an insult to the mitochondria, that can also create inflammation because these are autogens, right? When you age, for example, your NAD levels decrease. We've talked about this before together. You can go back and listen to our old podcast on NAD. 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 the whole series of problems that are linked to the aging process that makes your mitochondria really an essential pivot in all of this.

22:54And the immune system 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.

23:06Dr. Mark Hyman:So let's kind of unpack the immune system starting 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 firebomb city as opposed to our kind of smart targeted bombs. And that's called the innate immune system or the ancient immune system. And then there's the adaptive, that's also called the cell-mediated immune system, which we learned in medical school, which is mediated by the T cells. And the B cells. And the B cells. And then there's the adaptive immunity or the antibody immune system where we create specific targeted antibodies, for example, against COVID.

23:42Dr. Mark Hyman:When we check our COVID test, that's what we're checking as antibodies. Can you kind of unpack what those are, what they do, and how they change as we age? Great question. So think about, again, two systems, innate, first line of defense. And I promise you, everybody, we're going to get to the news to use here. I just want to kind of lay the groundwork here. 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 maybe a series of people who are, you know, arming the border, making sure nobody crosses.

24:15The, we talked about DNA in a 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 danger signal. Okay. During aging, for example, we have a disruption of the gut barrier. Some of the bacteria in our intestine can leach out into the blood and they cause inflammation. Simply that the disruption of your gut barrier will cause inflammation because some bacterial product are leaching out across, get in the blood, all of your cells see that and they think there's an infection. And so they activate the first line of response.

24:55So that's inflammation, by the way, is inflammation is that innate immune response.

25:02Dr. Mark Hyman:The chronic, sterile, age-related inflammation. Or acute as well. You have damage, you burn yourself, there's damaged tissue that's recognized by the innate immune system, it starts repairing. That part of the immune system, as we age, becomes hyper-responsive. It just sees problems where there's none. And that's a whole concept that people have talked called inflammaging. That's what I was getting at when I said related to the aging. 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.

25:40So imagine you get an infection with influenza, with a 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.

26:06Dr. Mark Hyman:Yeah, like a measles vaccine, right? measles, vaccines, or even infection that you have when you were a kid, herpes zoster. You can have a chickenpox when you're a kid. And for many people, you actually have immunity for life, although you should get your shingrix. Single shot. I hope we can talk about this because this is really fascinating in terms of the implication of some of these vaccinations. And that system, the whole immune system that's adaptive, depends on, in part, from your thymus. Thymus. Yes. Thymus is a gland that's called sweet breads. Exactly. Some of us— I had them the other night.

26:44Forget her. Yes.

26:45Dr. Mark Hyman:I hope it's going to help my immune system, but I don't think it works like that. No. So that's exactly what it is. Which shrinks as we get older. 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 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 decreases.

27:23Dr. Mark Hyman:You don't respond as well to vaccines. You don't respond. And for example, if you get a flu shot, you're going to get actually a specific flu shot for elderly, older individuals that will try to trigger your immune system more forcefully. And so this failure of adaptive immunity as you age is one reason why we saw during COVID-19 the risk of death increasing so much as a function of aging. Yeah. This is why 30 ,000 people, I believe, still die from influenza every year. The same thing with RSV. So there is an epidemic that no one talks about, which is the fact that older individuals die from viral and pneumonia.

28:09All 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.

28:22Dr. Mark Hyman:It's almost like 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 mount a response. Their cells do anybody. They're less able to mount a response to invaders. And so we can't fight cancer. We can't fight infections as well. And so we get all these different problems. That's a great point. You can respond to a vaccine in the same way. As you mentioned, the immune system, the adaptive immune system, plays an important role for what we call a tumor surveillance.

28:55So it goes around the tissues and it tries to determine, is the cell acting funny? Is it senescent? Is it zombie cells? If it's 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. 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.

29:32So the whole system degrades as we age.

29:35Dr. Mark Hyman:And so as people are listening, well, 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 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. Yes, it's very hard to sort of, first thing I should say also, why immune aging is so important.

30:09There'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 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 that's been shown in two different studies. So it's real data in mice creating these artificial tools that we have. It can make only a lesion in the immune systems, which means the immune system has a dominant role in our aging. That has been proven in another way. You might have heard about the new clocks that Tony Wiscore has generated, these organ-specific proteomics clocks.

31:00Is that Generation Labs? It's Vero. Vero Labs, yeah, yeah.

31:04Dr. Mark Hyman:Exactly, Vero. That's right. So what this company and Tony's work have shown is that they now can draw, from a blood draw, they can measure a series of proteins that are circulating that are reflective of the activity and the health of all organs. So they can determine... Like an organ clock, how old your brain is, how old your heart is, your kidneys. Because obviously, you know, you can be in incredible health in your whole organism. If your brain health is 20 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.

31:39So we want not to age at an oxidative rate in any organs. But what his data, they've gone back and analyzed 50 ,000 people from UK Biobank, huge data set 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 there are the two organs that are distributed.

32:05Dr. Mark Hyman:They're the sensory organs. Yeah, and your brain has ramification in the whole organism. Your nerves, your brain does not just sit in the cranium. It sends 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 going to be one of these... 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.

32:48And we still have that problem. But beyond this, let's say we can cure heart attacks, as I think we will in the near future.

32:55Dr. Mark Hyman:But also that's related to inflammation. Yes, but that's also, so maintaining immune health is going to be really critical. Well, you make an interesting point because the way I think about the brain and the immune system is the brain is the sensory organ for macroscopic things. The immune system is the sensory organ for microscopic things. So they're kind of mirrors. They're very, very important in maintaining tissue integrity and so on. So what do you do for helping your immune system age well? Dr. Burton. That's a tough one. So I think— Or at least a better phrase, what do you think the science best says we should do?

33:32Yes. First, we have to mitigate inflammation, okay? Because I think, as 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. The solution becomes the problem. The solution becomes the problem. And so mitigating this inflammation is key. And one area, for example, that I think there are multiple areas that we can talk about. Gut health, I think, is critical in this respect for me.

34:09And I tell people this is something that not enough people are talking about in the longevity field. 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 unpack this. I want to get into that. That's a topic we're going to get to. That's a great one for me. And one that I think we're not talking about enough.

34:33Dr. 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... The joke about me, my old job at Canyon Ranch was I was Dr. C 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. Agree, totally agree. And I think for most people, they're totally unaware. And 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, except maybe for Acumansia, most of those, we don't know how to use them or maybe Lactobacillus.

35:11Dr. Mark Hyman:And your diet is what creates your microbiome for the main reason. And you're focusing on prebiotics. These are foods, whether it's asparagus or just some artichokes or plantains. These are things we can eat that actually feed the good bugs. I agree. Or if you're not able, and actually the evidence points to the fact that most of us, or prebiotics would be all fiber. And most of us actually have an inadequate intake in our modern way of eating of fiber. And so I tell people, you know, if you have to supplement, supplement, but there are a growing number of good supplements that you can take. I mean, it's staggering when you look at the historical fiber intake of hunter-gatherers.

35:47Dr. Mark Hyman:It was estimated to be 150 grams of fiber a day. We ate at 15, and the average American, we should be trying to get to 30 by 40, 50 at least. My wife is from Germany, and I suspect you've traveled there when you eat a slice of bread from Germany. Yeah, you need a meat slicer. I visited a friend of mine in Germany when I was like 20-something, and and she had one of those like deli meat sizes in her kitchen like what is this for she's like i we for cutting the bread because it does a knife doesn't work yes yeah it's dense and that bread is you know but the other the other way is this bread also will force you to chew and will get you a large jaw which will stop sleep apnea so there's a lot of interesting things in terms of the the fact that our diet has become almost like semi-liquid yeah uh creates all of these problems in terms of facial features and so on.

36:36Dr. Mark Hyman:That was the work of that dentist who went around, I forget his name right now, the guy who went around and saw all the indigenous cultures and looked at all the teeth and the tooth. I mean, 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 have perfect teeth. They don't need dentures. 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. Absolutely. I'm reading James Nestor's book, Breathe. Yeah.

37:10Or Breath. I don't know. And there's a whole chapter on this. There's this sort of adventurer who was the first one to actually visit American Native Indians. And what was one of the things that struck him the most is 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 a heart has implication not only in terms of our microbiome, but also our tooth structure, our ability to breathe through our nose and so on.

37:53Dr. Mark Hyman:So whole foods, fiber is the root of everything. Yeah, so phytochemicals, fiber, whole foods, getting rid of processed foods, sugar, all that's going to 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? This is the foundation. And I think, you know, I - Sleep, stress, exercise, food, toxins, microbiome. Human connection. Human connection, yeah. All of those is, for me, the foundation of longevity medicine. And, you know, people have argued, well, this is not sexy. This is not what people want.

38:25They want supplements. They want drugs. They want a shortcut. And I'm all for shortcuts, but I believe it just doesn't work. 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 in talking is one that is a bit contrarian to what some of my colleagues are advancing in the longevity field. I'm as excited as anybody by what we're going to be doing 20 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.

39:06Not everything needs a pill.

39:08Dr. Mark Hyman:Yeah, one of the most interesting studies I ever saw was a whole field of sociogenomics, which I kind of came up with on the term myself because I kind of saw Paul Farmer's work in Haiti and how he helped people and using community health workers to help. And I just came up with this concept. But 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 that 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.

39:41I love that whole aspect. Yeah, it's really interesting. And it's…

39:45Dr. Mark Hyman:More cuddle puddles. It's incredibly frustrating for me that we know from the happiness studies, for example, that the biggest factor determining your longevity is your social connections. Yeah. number of loving relationships you have, your sense of purpose. The problem is that these are also the hardest ones to study, especially in animal models. I can go ask a mouse what its sense of purpose is, living in a little plastic box and eating the same food that looks totally disgusting. So we've been talking actually at the back about creating a center for the psychobiology of aging, which would really try to...

40:27At the end, everything is driven by molecular mechanism. I mean, we are biochemical feature.

40:33Dr. Mark Hyman:Could you reproduce like a whole natural mouse environment? Yes, people are doing this. It's kind of interesting. Like a cage. They're creating these like really, and we study longevity, by the way, in these mice that live like these prisoners. I mean, 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 youth.

41:11Dr. Mark Hyman:Amazing. All right. This is so good. So I think we kind of got a good dive on the immune system. Let's kind of switch over to mitochondria and help us understand how mitochondria and cellular energy are so central to aging. Because to me, they're kind of like the final common pathway 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 yes so where do we start let's start with like what why are mitochondria and cellular energy so important to aging the big reason that everyone uh knows is the most people agree on is the energy energy requirement so everything that we do is dependent on energy.

41:55People think about moving your arms, thinking. Everything that we do is depending on generating energy. Typically, we get that energy from our food. 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. We talked about free radicals. That really induced damage.

42:46Damage 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 our cells little monitoring mechanism that constantly look at everything, make sure everything is fixed. As soon as... Like sensors. 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 code that encodes every one of our cells. It sends the reason that if you're making a damage and you're creating a mutation, you have the potential to change the code.

43:28And essentially, so if you allow this to happen all the time, eventually the whole system is going to go awry. So there are human mutants who are people who carry a mutation from their parents where they are not able to repair DNA damage. They typically live until 20.

43:45Dr. Mark Hyman:You're the progeria patients? 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, many of them with very shortened lifespan. So 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 an extremely precise manner to function. If it becomes a little unfolded, all of a sudden, it's creating problems. And that's one of the hallmarks of aging is protein damage.

44:24Yes, 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 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.

45:06And so this antagonism between repair and reproduction is really at the root of aging. And so as we age, the mechanism of production of this energy starts to become limiting. We mentioned these bacteria, these mitochondria become old.

45:27Dr. Mark Hyman:But there's a way to repair them and renew them, right? 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. Yeah, it's like autophagy, but it's for your mitochondria. Autophagy is where you kind of eat yourself and clean yourself up. And autophagy is activated when you're resting and actually allows you at night to actually repair a lot of the damage. And what's amazing about autophagy is that it's a self-eating mechanism that specifically targets what's been damaged. So imagine you're not eating, so you still need energy.

46:02And that energy now has to come from the inside. your system has a mechanism that goes to clean up the attic first. It doesn't destroy the kitchen. It goes into the attic and says, okay, what's all the garbage here that I can still resell and make a profit without actually touching the kitchen? 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 these repair mechanisms, we don't repair perfectly. We've repaired pretty good.

46:40During our 20s, the rate of repair is such that if we were to continue repairing at the same rate, we would live to 1 ,000 years old. So during our 20s, we're actually doing incredibly well. The problem is as a little damage accumulates over time, eventually some of the damage might actually target the repair mechanism. And we know aging is not a linear process. It accelerates. the older you get the faster your aging process and so the whole idea of activating reactivating mitophagy because eventually as you get old mitophagy becomes limiting as well it doesn't function as well so exactly

47:20Dr. Mark Hyman:when I think about this it's such an important kind of framework to think about the sort of energy of the cell because it really runs everything And we kind of do know that everything that impacts aging also impacts the mitochondria and vice versa. And there are levers, though, to really take care of your mitochondria. We talked about NAD on our last podcast, but there's other compounds that induce mitophagy and that are, we mentioned postbiotics earlier, which are essentially compounds that you eat from food. that get metabolized by your bacteria and they produce downstream molecules that have function in the body, which I think is a miracle.

48:04Dr. Mark Hyman:Just when you think conceptually about it, that you eat stuff and then it creates like literally a medicine that turns on different signaling systems in your body to help you repair, renew. And I think from my perspective, and it sounds like you think the same way, when I think about aging, I think the body has these innate systems of repair, renewal, regeneration. We just burden them and we don't take care of them. 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.

48:37Dr. Mark Hyman:And I have this joke, I call it a symbiotic phytoadaptation. We symbiotically evolved with plants and use their compounds to regulate our biology because we're lazy. 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 elagitannins that are in, you know, walnuts or berries or whatever. So kind of help us understand how, for example, this molecule, Eurylithin A, which you published on, and we'll link to the papers in the show notes, and which I, by the way, take every day because the literature is impressive on it.

49:10Dr. Mark Hyman:What does it do and why is it getting so much attention now? And we kind of learned about it more in the context of exercise, improving, you know, exercise capacity, VO2 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 a, it's a really cool story because it's one really, I would call it a sort of a human ingenuity. And so in some way we've known for a long time that pomegranate juice is actually healthy for people.

49:47And there's a whole, you know, There have been studies showing that consumption of pomegranate juice actually confers some health benefits. What was not clear is what the mechanism. So, some scientists, a good friend of mine, Johan Aurex, who works in Lausanne, actually went and looked for what is in pomegranate juice. And they found these illogitanins, these compounds. What they also realized is that these compounds are not acting by themselves. They are actually metabolized by your microbiome. And the product that is made by your microbiome is called urolithin A. Now, the catch is only about 35 % to 40 % of people is microbiome, because remember, all of our microbiomes are different.

50:34And some 60 % of people's microbiome is not able to make that conversion.

50:40Dr. Mark Hyman:We've trashed them because of our diet, because of antibiotics, because of toxins, all this stuff. So having a rich, you know, most of us have more than a thousand different species of bacteria in our guts. And the problem, the complicating factor is most of us have different species. So you cannot compare your microbiome and mine, even though we might both be very healthy. They can change. I've seen the study where you have people on a vegan diet or a meat paleo diet. Their microbiome is literally in the same person. They can change. Yeah. We don't know how to read it well, but we know certainly what upstream factors can actually yield a really complex and rich microbiome.

51:21Dr. Mark Hyman:As you know, I talk a lot about protein, especially as we age, but not all proteins are the same. Collagen is actually the most abundant protein in your body. It's the glue that holds you together, your skin, your joints, your bones, your connected tissues. And after the age of 20, our bodies start producing less collagen, which contributes to the changes we notice in skin, in joints, and in bones over time. Traditionally, we got collagen from nose to tail foods. Think slow-cooked stews, bone broths, and connective tissue. But most modern diets don't include those foods, which is why supplementing with high-quality collagen source can be really helpful.

51:54Dr. Mark Hyman:And that's why I like Paleo Valley's 100 % grass-fed bone broth protein. It's made from bones of grass-fed and finished cattle raised on American regenerative farms. and it's made simply with water and bones. No harsh chemicals, no fillers, and it's rich in collagen and glycine, which is an amino acid we often don't get enough of. Now, collagen supplementation has been shown to support skin health and joint comfort, and glycine may have a role in overall health as well. I'll often add it to my tea or a smoothie, and the chocolate flavor even makes a delicious hot cocoa. It's an easy, ancestral-inspired way to support your body with collagen every single day.

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53:05Dr. Mark Hyman:Now, these compounds are studied for supporting healthy immune balance and longevity, but it doesn't stop there. Each chew also includes vitamin C, vitamin D, magnesium, and zinc, all nutrients your immune system depends on, especially when you're pushing hard. And because they're chews, not pills, they're convenient and delicious, perfect for your bag, your desk, or wherever the day takes you. If you want a simple way to support resilience, energy, and focus this summer, try HTB Immune Energy Choose. Go to bigboldhealth.com slash drhymen, that's D-R-H-Y-M-E-N, and use the code HYMAN15 to save 15 % off your first order.

53:41Yeah, 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 an input from a food product, from a plant, pomegranate juice, it gets transformed by a fraction of us into a product that has immense benefits. So, a company was founded based on this. Amazantis actually sells this product, and we've been working with them. Full disclosure, I sit on the board of that company as a scientific advisor, but I always tell people I don't sit on the board of supplement company if I don't believe in the science and if they're not willing to actually conduct clinical trials and that's one thing i think is commendable for amazon is they've been going through clinical trials one one at a time yeah to actually document and prove the efficacy of what i agree and they're a sponsor

54:35Dr. Mark Hyman:of the podcast and that's why also i i don't let everybody sponsor my podcast you imagine all of you last week because i think i want stuff that i know has has legitimate science behind it and you know this is published in major journals like new england journal or jam or other cell So I think this is important. So to me, I'm not opposed 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 have, and that's how medicine has moved forward. So that being said, we've worked with them on a couple of studies. We still have another study going on with them.

55:06So urolithin A has this remarkable ability to activate mitophagy. And mitophagy is not sort of the, 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 studies that we've done was looking at the human immune system of older 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, I would say, what anybody would call a rejuvenation of the immune system.

55:47Dr. Mark Hyman:I mean, I think 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 health, but there's even better markers. But what are the things that you looked at that indicated that it helped to reduce the inflammation process? Yeah, actually, in our case, we, well, some cytokines, we measured the presence of different cytokines, TNF-alpha, IL-6, IL-1. And I don't remember exactly which ones were changed, but some of them were. And cytokines are the messenger molecules of the immune system.

56:21Exactly. And IL-1, IL-6, TNF-alpha are pro-inflammatory molecules. So the higher the level, you know, the higher the inflammation. What we focused on in my lab and with our core at the back was on looking at the adaptive immune system. 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.

56:49Dr. Mark Hyman:And just in English, naive T-cells are kind of cells that haven't made the antibodies yet. They haven't kind of... They haven't been activated to... To develop antibodies. The T-cells, the B-cells would be making the antibodies. So these are the T-cells. That cause the B-cells to make the antibodies. They help, but they also by themselves can generate what we call cytotoxic T-cells, CD8 T-cells, which are the other. So the innate immune system, the adaptive immune system has two arms, T-cells and B-cells. The T-cells are making, actually they can kill bad cells. The B-cells can actually secrete the antibodies, which help in the immune response.

57:31Dr. Mark Hyman:And so the urolithin A works on the T-cells? It worked on the T cells and actually increased the ability of these T cells to recognize their targets. Now, this has implication not only for the person who's thinking this, but think about, you might have heard about the CAR T cells that are used now for cancer cells, where 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 re-educate these t-cells goes down and so this would have even an implication for cancer yeah because they did it in vitro and show that these car t-cells were actually more effective so you know 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 anthony affect like the whole process of longevity, the muscle, the inflammation?

58:27Dr. Mark Hyman:What do we know about it? Mitochondria are not just present in the immune system. They're present in every cell. And so think about the concept of - Except for red cells. Except for red cells, exactly. They don't have a nucleus. They don't have mitochondria. I think they have mitochondria. Oh, they do? When we think about mitochondrial function, it's not restricted to the immune system. It's pretty much every cell that has to balance repair and dividing and moving forward. So when we think about urolithin and its effect, they're going to be pretty much across the whole organism. And I mean, we focus so far on the muscle where we could see increased endurance in people, actually humans on urolithin A.

59:10We've seen increased immune responsiveness. 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 this is a molecule that's not just targeting the immune system or an organ.

59:27Dr. Mark Hyman:You call it pleiotropic. 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 anti-aging effect. Yeah, I mean, I think this is interesting because we're often looking at drugs that affect a single target. They're a single molecule, a single receptor, a single target. But when you look at these longevity interventions, they have diverse effects across all these different systems. So a compound like urolithin A has many different effects across the system. That's an important point. And it goes back to this whole idea of what we talked about, geroscience.

1:00:02What does geroscience really mean when we talk about aging being at the root of everything?

1:00:06Dr. Mark Hyman:Like geriatrics, like gerontology. Yeah, that's the root of it. But it's the root of it. That's what that means. There's another example, because the way we practice medicine is based on a model that dates back to the 17th century when we discovered organs. You go see a heart doctor, you go see a neurologist. There's a National Institute of Health, which has a National Heart, Blood, and Lung Institute. It's a National Institute of Organs. 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 17th century model.

1:00:41Now, when we talk about urolithin A, it's not that it's going to help your immune system. It's going to help everything. Same thing, think about rapamycin, which is another darling from the longevity field. Its target, 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 the shift that longevity medicine is doing from sort of organ-based reactive model to a sort of system-based proactive.

1:01:17Dr. Mark Hyman:Yeah, you treat the system, not the symptoms or the diseases. That's essentially what functional medicine is. It's what I've been doing for 30 years, and it actually works really amazingly well. You really get to the root cause, like you were talking about the root, not the branches and the leaves. And that's even the paradigm we use to describe what functional medicine is. We treat the root and the trunk, not the leaves and the branches. As a physician, I've been a fan of this approach of medicine. I think what longevity has done is to add a little bit of a more exciting aspect, frankly. And I think my hope is that this is a reintroduction of many of the concept of functional medicine through the eye of longevity.

1:01:59And for some reason, it's resonating more with people. It's become kind of, you know, longevity has become sort of a buzzword, which scares me also to some degree. But I think it's a wave that we should ride because it will, in the end, change the care for patients and make it much better.

1:02:15Dr. Mark Hyman:I agree. And I think, you know, the way I think about functional medicine is a heuristic. It's just a tool that we use to think about things. It's not the thing itself. Because 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 functional systems that we describe in functional medicine, they almost map perfectly across the hallmarks of aging. Mitochondria, microbiome, nutrient sensing, all these things are all part of this. And so we may improve that model and become smarter and smarter, especially as we start to dive into the complex biology that we barely have scratched the surface There's a proteomics and transcriptomics and metabolomics and the microbiomics and the whole, that's like, you know, at Function Health, we do like 160 biomarkers at first flush and there's more you can add on.

1:03:04Dr. Mark Hyman: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, there's thousands of metabolites. And it's almost like incomprehensible. But now with big data science and with AI, we can start to make sense of this. I could not agree more. And I think this is... Because no matter how smart you and I are, we're never going to understand it all. No. And we're generating data right now in patients at a rate that is beyond anybody's comprehension. And I'm always comparing the state of medicine today.

1:03:41And 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 20 measurements or your typical annual visit, 20 or 30 measurements. And that's what most people will rely on. Their hemoglobin A1C, their LDL, not even ApoB. Their fasting blood sugar, maybe their A1C and so on.

1:04:04Dr. Mark Hyman:You're lucky if you get an A1C. Yes. If you're not diabetic. Yes. And so, and a stethoscope, you know, and a little bit sort of something that we use. 17th century medicine. Something that we used to do, you know, 50 years ago when we were being trained. Yeah. Today, I mean, we can generate out of a single blood jar, hundreds of thousands of different data points. And I think a lot of the work that we're doing at the Buck right now is trying to integrate all of this data because we're generating it with AI. And really making sense of it. Yeah, making sense of it. So these are early days, but I cannot help to be incredibly optimistic of the fact that in 10 to 20 years, we will do, we're starting, you know, starting with function help.

1:04:47others in different ways, really to generate a lot more data.

1:04:52Dr. Mark Hyman:Yeah, we've got like 80 million biomarkers we've tested in the first few years, and we're just getting started. And, you know, I remember sitting on a panel at Cleveland Clinic with Stan Hazen, 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, But when you think about that, it's like our microbiome, like you said earlier, is a completely neglected area of medicine. Gastroenterologists don't even pay attention to it.

1:05:25Well, I'll tell you another piece of data which I keep reminding myself of is half of your immune system. So your immune system is distributed across the whole body, but half of it is in the intestinal. Yeah, pyre's patches.

1:05:39Dr. Mark Hyman:Why? Because it's where you're interfacing with the outside world. With the bacteria. You're one cell away from 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 kind of help take care of you. 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, frankly. This is an organ, an additional organ in terms of weight.

1:06:11It's pounds. That's three to five pounds. People don't realize these are pounds. This is a big - Pounds of poop. Pounds of poop. And all of these bacteria are digesting your food. In many cases, they pre-digest what you've eaten. They're generating all of these secondary products. All of these products go into the wall of the intestine, and they educate your immune system. So this interface there is really, I would say, one of the still big black box of what -

1:06:42Dr. Mark Hyman:It's interesting. And in functional medicine, we've been testing organic acids for years. And part of the things that 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 things that are going on. It's quite interesting. And we treat people based on that. And it's pretty cool stuff. I mean, Eric, this is such a great conversation. I actually want to talk to you more. I'm not going to do a three-hour podcast with you this time. We're going to break it up. I want to talk about some of your new research going forward.

1:07:08Dr. Mark Hyman:I think we're going to maybe do another podcast on this because it's a whole topic in and itself, which is how do we measure biological age? And I'm just going to set the stage and I want people to come back and listen to the next podcast, but we are trying to figure out, let me say we, the scientific community is 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.

1:07:38Dr. Mark Hyman:We use one in function, which is based on Morgan Levine's sort of calculation and biological age. Uh, and, and it's, you know, it's, it's an approximation. And I say, you know, if you, you do the same clock over and over, you're going to get the same kind of variation, but, but they all widely differ. And one clock, you were 29 when you're 69. It's like the same thing I've seen. And 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 going to set the stage of looking at the clock that has to do with your naive T-cells.

1:08:07Dr. Mark Hyman:And this seems to be more of a stable clock that you can kind of track. It doesn't vary so much. So we're going to come back and do a podcast on that. I'm super excited about it. We're going to put a link to the show notes. We're going to do a full show on clocks. Yeah, I think we want to do a full show on clocks. One area, I think is really, you know, if I can say one more thing about these clocks, why is that important? As we move from this reactive to proactive medicine. The way most people live their life is they have their lifestyle. Their spouse or their children might tell them, let's try to do this and exercise more.

1:08:44Everybody's living their life what I call flying blind. You have your doctor's visit annually. You might get a few samples. But eventually, you get into your 50s, your 60s. if you're lucky and you've done the right thing, you're going to go right through. If not,

1:09:00Dr. Mark Hyman:you get a heart attack. And so the question that this whole new reinvention of medicine, functional medicine, longevity medicine is really occupying itself is this, can we accompany you starting at age 20, 25, measure you every, no, maybe every day using wearables, using blood sampling, you know, the technology is going so quickly. I don't know how we're going to be doing this. The idea for me is really this constant monitoring. Nobody would fly a plane blind today. We have incredible, but we fly our health. Episodic medicine just doesn't make sense. We fly our health blind. Yeah. And we go to the doctor, we're nervous, our blood pressure is too high.

1:09:41We go home, maybe it's too low. So this whole idea of everyday measurement, hopefully in a way that's totally invisible to you, is the future. And so these clocks represent sort of the integration of many of these variables that are going to tell you you're flying not completely blind. It looks at age 30 that you're on your way to getting a heart attack at age. We can do this now. 15 years in advance, we can identify the first signature of disease 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.

1:10:16That's really the way medicine is going to change. And I think the clock for me at this point are an incredibly promising direction.

1:10:25Dr. Mark Hyman:Yeah, it's true. And I think what you're saying is right. I mean, episodic care, waiting until you have something doesn't make any sense. And I think that's really our mission at 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 uh or a band or even continuous glucose monitors and there's going to 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 can see it coming a mile away and that's that's you what I get excited about.

1:11:11Yeah, same for me.

1:11:12Dr. Mark Hyman:Thanks so much, Eric. Thanks for doing your work and great to see you again. And we'll have you back soon. Likewise. Okay. Thank you. If you love this podcast, please share it with someone else you think would also enjoy it. You can find me on all social media channels at Dr. Mark Hyman. Please reach out. I'd love to hear your comments and questions. Don't forget to rate, review and subscribe to The Dr. Hyman Show wherever you get your podcasts. And don't forget to check out my YouTube channel at Dr. Mark Hyman for video versions of this podcast and more. Thank you so much again for tuning in.

1:11:40Dr. Mark Hyman:We'll see you next time on the Dr. Hyman Show.

1:12:08Dr. Mark Hyman:professional advice or services. If you're looking for help in your journey, please seek out a qualified medical practitioner. And if you're looking for a functional medicine practitioner, visit my clinic, the Ultra Wellness Center at ultrawellnesscenter.com and request to become a patient. It's important to have someone in your corner who is a trained, licensed healthcare practitioner and can help you make changes, especially when it comes to your health. This podcast is free as part of my mission to bring practical ways of improving health to the public, so I'd like to express gratitude to sponsors that made today's podcast possible.

1:12:39Dr. Mark Hyman:Thanks so much again for listening.