Decoding Longevity with Dr. Eric Verdin of the Buck Institute

00:00:17
Speaker 1: Pushkin.
00:00:24
Speaker 2: This show is not a substitute for professional medical advice, diagnosis, or treatment. It is for informational purposes. Please consult your healthcare professional with any medical questions. Also in this show, we use women as shorthand for people with XX chromosomes. We understand sex and gender are more complex and acknowledge the experiences we describe reach beyond that word.
00:00:54
Speaker 1: For most of human history, the quest to defeat aging was the stuff of myth and magic, elixirs, fountains of youth, alchemy shortcuts. What's changed in recent decades, and especially in the last several years, is that a scientific revolution has taken hold. Longevity science has matured, giving researchers exciting new approaches to an old question, how do we live not just longer, but better. Some of the most groundbreaking research in this space is happening at the Buck Institute for Research on Aging in northern California. It's the world's first research institution dedicated solely to understanding and extending human lifespan. At the center of that work is doctor Eric Verdon. He's the president and CEO of the Buck Institute and one of the world's foremost experts on the biology of aging and Doctor Verdon is more than a leader at the Buck Institute. He's also a physician and gero scientist who has published more than two hundred and fifty papers on the immune system, the molecular mechanisms of aging, and epigenetics. I've been following his work for years and I was thrilled to have him as a guest on the show to unpack some of the buzziest topics in this space, from NAD to golp once for longevity. And I was taken by his candor as he shares with us what he's tried himself, what he believes has potential, and what trends he's decided to skip all together. Here's our conversation. So let's start a little bit with some background. How did you get interested in this area of medicine.
00:02:44
Speaker 3: I had a life changing experience, which was I spent the last year of medical school at Harvard and you know, small boy, coming from a town in Belgium, first person in my family to go to college. I didn't even realize what I was getting myself into, and I was just struck by the quality of the students, the quantity of the teaching, and it just only sort of re emphasized my desire to do research. Around nineteen nine ninety five, I started switching my lab more and more towards aging and just really enjoyed those first few years where we were essentially rewriting what we understand about the aging process. And all this work was done at the Gladstone in Stitute that you see SF in San Francisco, and about ten years ago I was offered the position of ahead of the Back Institute, which was at the time and still is, i would argue, the largest and the earliest institute focused on the biology of aging. Over the last ten years, I've been sort of sharing my time between administrative duties, which is running the institute and representing it and also continuing the basic science understanding the role of epigenetic regulation in aging.
00:04:00
Speaker 1: What was that revolution that was occurring in research that you refer to in terms of the research and aging. What was going on?
00:04:08
Speaker 3: First of all, I'll paint the picture of what we think aging was. Most people in the field of aging thought aging was sort of a stochastic, a random process where cells in your body go awry, cell in your heart doesn't work anymore, it dies. You have a little less heart muscle function, something happens in your brain or cell die. So this kind of random process where under the influence of external forces. And these external forces are oxygen, which is, you know, generate its oxidative, stress, gravity, UV, light comes from the sun, gamma rays, so all sorts of forces that exist that are deleterious to our organism we thought were inducing random damage. That's what aging was. I make the analogy to a brick wall. Imagine that your organism is a brick wall, where each brick is a cell, and that wall is subjected to the environment win sun. Eventually, you know, we know what happens to a brick wall if you don't tend to it for a long time, one brick will get damage, it will fall out, You'll make a little hole. Another brick will fall out another place. That was our vision of aging. And frankly, when I told people that I was moving into aging research at the time, several of my sort of more senior advisors told me shouldn't do this. This is sort of a backward area of science. You know, nobody makes a successful career studying aging.
00:05:43
Speaker 1: Thankfully, doctor Burden didn't listen to them. And by the nineteen nineties there were breakthroughs and other animals, namely really tiny worms called sea elegance, that significantly changed the way we thought about aging.
00:06:01
Speaker 3: And so what happened in nineteen nineties is people started identifying single genes that could control the whole aging process. Okay, and I'll refer to the work of a good friend and colleagues, India Kenyon. What she had found is she could make a point mutation. So you change a single base in the genome of a little worm that has billions of bases, and one single change could actually make the animal live twice as long. And that just blew people away. How could it be? Why doesn't evolution actually optimized this so that we all live as long as we could. Why don't animals live to their full potential? So this was shown in the little worm and see elegance, It was shown in fruit flies, and then it was shown eventually in mice, and it painted a picture that was completely different where aging was much more regulated. If you find a single gene that changes aging, the implication is that maybe you could make a drug targeting that one single gene activated, make it work better, and therefore you could affect the whole aging process. So it really changed aging from a totally passive process to one that we could actually control. And I'll go back to my wall analogy. What we had not appreciated is to what degree behind the wall there is an army of masons that are constantly fixing up the wall. Okay, just imagine that you find sort of a great mason. He's going to have an impact on the whole wall. He's going to fix bricks everywhere and so that the wall is actually going to stay in place. Going back to the findings, people initially thought, well, this is an exception, this is something really unique to see elegance a little worm and it just doesn't apply to mice or higher organism. But it does. And today we have close to six hundred or seven hundred genes in the worm that actually regulate aging, and it's actually quite easy to increase lifespan. What I'm trying to say is that it's changed our appreciation of aging as a regulated process that we can actually tweak. The finding of all these genes that control aging is is the equivalent of identifying dials. We can turn them up and turn them down, and the animals live longer or shorter.
00:08:27
Speaker 1: What he's describing here is how much of scientific discovery actually works. Studies and animals that, through rigorous trials and testing eventually get examined in humans. The same arc has played out with epigenetics, the idea that aging isn't just written into our genes, but also written onto them through modifications that can be measured and potentially influenced. I want a doctor Verdon to walk us through how the field of epigenetics has evolved and how it's broadened our understanding of the aging process. So you talked a little bit about epigenetics. What is epigenetics.
00:09:06
Speaker 3: Epigenetics is actually an amazing area of biology. Every cell in your body and my body have the same DNA. Okay, so that's the code of life. But obviously our cells doing very different things. You have some cells that are heart cells, some cells that are neurons in your brain, you have blood cells that fighting infection. How does the body generate such different functions with the same blueprint? And that's where epigenetics comes in. So genetics is the sequence of your DNA, It's the same in every cell. Epigenetics is on the side of genetics, and it allows a given cell to have the same amount of DNA to turn on different programs. Okay, so imagine you have a whole set of genes that are making all the proteins that will make us cell a heart cells. Well, those genes will be turned down in the heart cells. The process that regulates what genes are turned on or off is so called epigenetics. It turns out we have this image of ourselves that we think we are fixed, but we are not. As I tell people, you know, when you come into work in the morning, you're not the same person as you are when you leave at night for two reasons. One, you've gone through your whole day, whatever, people you've met, what you have eaten, whether you've been in the sun, all of these interactions. We are constantly in tune with our environment. So epigenetics helps in two key ways. It helps in defining cell identity. You know, we have thousands of different types of cells in our body. In the blood, for example, we've enumerated different cell types, each with their specific programs. So that's the first thing that epigenetic does. The second thing that epigenic does is allows you to tune your cell program as a function of the environment. Okay, when you wake up in the morning, if you get exposed to the sun, you will get light in your eyes that will go into your brain and will activate all kinds of programs. We have hormones that are going up and down throughout the day's so called circadian rhythm. All of this is regulated by epigenetics. And so one of the things why epigenetic is relevant is that we know that these processes that control cell identity and control self function do degrade as we age. Your heart cells start behaving a little more like a neurons from your brain, and your neurons and your brain starts maybe behaving a little more like a heart cells or an immune cells. And obviously optimal biological function is relying on everything being precise and perfect. So this is why epigenetic has become so prevalent in understanding the aging process.
00:11:59
Speaker 1: This is where lifestyle impacts the aging process. Right does a lifestyle like exercise and nutrition and healthy mindset and social engagement changes how our genes are expressed through epigenetic that's my gnecologic oncology women's health expert interpretation.
00:12:15
Speaker 3: Actually, I'm glad you said this because this is the point that I forgot to make. So what is the role of your genes versus how you live in your life expectancy? Right now, the latest data seems to be saying that it's about fifty to fifty fifty percent genetics fifty percent lifestyle. The question is how does your lifestyle change your life expectancy? It's exactly by tweaking these epigenetic processes and making them more better. So that's the whole idea.
00:12:43
Speaker 1: What are the genes that are involved in agen I would think that this would go back to kind of the superagers genetics, right What types of genes are they repair genes of DNA? What do these genes do that help us have healthy longevity?
00:12:57
Speaker 3: Great question. Essentially, any gene that's involved in repair. You mentioned DNA damage is a good example. Under the influence of gamma rays that come from the cosmos or uvlyte, those tend to induce DNA damage. Okay, and your DNA gets constantly repaired so that the sequence is faithful. We now know that there are families or individuals who carry mutation in some key specific DNA repair pathways. A lot of our energy is actually involved in repairing DNA, making sure it says Christine, and if you have a mutation these genes, many of these patients actually don't go past twenty and some of them actually show accelerated aging. It's not only about repairing DNA, it's also repairing proteins or proteins a long string of amino acid. They have to be folded in a very precise manner. Sometimes they get misfolded. This misfolding of the protein actually triggers a stress response, and those proteins get refolded by a whole series of other proteins called chaperones. So there's a whole there's a whole process of repairing. What other genes are involved in aging. Epigenetic regulators are one of the groups that can really play a role atophygy. You know, this is the process of self eating, which is also a process of repair. These genes are also involved in aging. As I mentioned, there's a whole series of genes. Anything that's involved in cell maintenance and repair or protection against damage appears to be involved in the aging process. Last, but not least, metabolism is intrinsic to that whole thing. It turns out that joining metabolism. When we are taking food in and digesting it, that tends to generate what we call radical oxygen species or free radicals, and those can be damaging as well. So there's a whole list of interesting genes that many of them we are actually studying and targeting specifically to adjust the aging process.
00:15:08
Speaker 1: We need to take a quick break, but when we return, we'll be diving into some of the hottest topics in the field of longevity science na D, rapamizin, golp ones, and more. Stay with us, Welcome back to the show. You're going to hear us talk a lot about na D, and for a good reason. It's one of the hottest topics in the longevity world these days. But what often gets lost in these discussions is the fact that NAD is actually a naturally occurring metabolite, a tiny molecule present in every cell of your body. I ask doctor Verdon to unpack the crucial role in AD plays in our biology. Then we'll hear his take on the current trend of people taking INNAD precursor supplements to boost longeva. So let's talk about some of the cellular components and some of the words that people will hear, you know, when they're reading on social media or just reading in the popular press. Can you unpack some of the mechanisms related to some of the words that we hear, like NAD, h DEX that you already mentioned, or two ons. Can you define these a little bit for us and let us know why we should care about them.
00:16:35
Speaker 3: I'll start with NAD. That's a really good one. NAD is a metabolite, so it's a small molecule. It's not a protein. It's a metabolite that is involved in energy transfer as present in the cells, and it carries energy from one part of the cell to the other. It also plays a key role in protection against oxidative stress. As we mentioned, why is an AD important because it's a co factor for many enzymes that are involved in metabolism, and we know any D levels decrease during aging. So there's been a lot of interest in trying to see what are the consequence of this. Now. One of the targets of NAD is a family of protein called certuins. You mentioned them as another one of your questions. Sirtuins are epigenetic regulators, some of them are. I mean, there's about the seven sirtuins. At least three of them are epigenetic regulators. And what's really interesting about certuins is that they exert global anti aging effect at the cellulary levels, so they're protective. They're part of the repair pathways that we talked about earlier, and they are NAD dependent, which is really how you link. You know, why is NAD important. One of the consequences NAD levels decreases, the sirtuins become less active and therefore you run into some problems. So that would be a short introduction to NAD and sirtuins.
00:18:01
Speaker 1: So NAD Taking NAD helpful or not helpful, because I think that we have to talk about taking NAD as a supplement as a separate actually more nuanced research you're looking into right.
00:18:14
Speaker 3: My lab and many other labs showed that ND levels decrease during aging. So the question is first y and second can recorrect it? The field jumped down the first solution, which was to provide precursors to ANAD. So you can make an AD in multiple ways. One is from amino acid tryp to fan or also from some vironulmin and nicin. But we know that these processes are not great limiting. That is, you know, in most people, you have enough protein, you have enough trip to fam, you have enough nicin in your diet so that you don't really need additional So people focused on two precursors called nr nicatinumine riboside and NMN nicotinamine mononucleotide, and both of those are available commercially, and we and others have been able to show that if you give this to an aging animal and you can restore the levels of ANAD to a normal level. And the prediction was that this should help. And so giving these precursors makes sense because they can get into the cell and they lead to a rise in NAD. There is right now a sort of a new fad, which is the idea of giving NAD itself either orally, intravenously or subcutaneously. From my standpoint and from most people who work on NAD, this doesn't make any sense because NAD does not cross the cell membrane, so if you eat it, if you injected it travenously or subcutaneously, it doesn't give you ANAD. Maybe it makes sense commercially to the people who are selling these products, but from a scientific point of view, it's not the way to correct NAD levels. What my lab has been working on for a number of years, not ten years, is why are NAD levels decreasing during aging? And we've identified a new molecule called CD thirty eight, which plays a key role in the immune city, in the blood vessels, in the brain. And what CD thirty eight appears to do is to choose up ANAD and its level increase during aging for reasons that are not entirely clear. So we think, and we've demonstrated one of the reasons and ED levels decrease during aging is because CD thirty eight level increase. I make the analogy to a sink that's full of water. So imagine your body is the sink and the water level is your NAD levels. That level decreases during aging. What we do with the precursors and R and NMN is we sort of pouring more water in this leaky sink. What we've done is to identify the source of the leak, which is CD thirty eight, and so our approach and I've created a company called Nabat Therapeutics, which is pursuing this is to actually target CD thirty eight and block it. And we now have some level molecules that are actually going into the clinic for the first clinical trial later this year that are blocking CITY thirty eight, and we know those actually lead to a restoration of NAD level in aging animals, and they seem to be having a whole series of really global, quite remarkable effect.
00:21:25
Speaker 1: That's so interesting. What are the global effects that you're seeing from these CD thirty eight inhibitors, you know, the blockers of NAD destruction.
00:21:33
Speaker 3: I'll tell you some of the strongest effect that we see are in the brain. The drugs actually, the CD thirty eight inhibitors increase lifespan, so that's actually the first thing as an aging scientist that we want to see. So they do increase lifespan in animal models. In the brain, we have evidence that they actually preserving memory and you know, so much anxiety right now in everyone who's aging about maintaining good cognition. We find that the animals on these drugs actually maintain brain function at a much higher level than untreated animals. So I think there's going to be a whole series of really interesting applications in the future.
00:22:14
Speaker 1: And then in terms of the impact of exercise on NAD. I kind of remember reading this Nature article about five years ago that found that exercises associated with higher NAD levels in older adults. Any other lifestyle factors to naturally increase your NAD.
00:22:31
Speaker 3: I don't think the jugs, the precursors, or the supplement themselves would induce cancer, but there's been some concern that they might be accelerating. Yes, fasting calorie restriction is another one that appears to be working on NAD levels.
00:22:48
Speaker 1: Do you take NMN r NR yourself?
00:22:52
Speaker 3: No, I don't. I'm trying to be sort of entirely consistent with my own work, and our own work says that the problem is not a lack of water, it's the leaky sinc I do worry about pouring in more water and the leaky SYNC. The reason being that, for example, we talked about C eight, it degrades NAD, but also degrades NMN. So if you have an elevated level of CD thirty eight and you're pouring a MN by taking a supplement, you're gonna turn through the whole system. And so this has some consequences. Without getting too technical, I used to take NMN to be fully transparent, and I saw my homo syst in level going up. As soon as I stopped it, my homo systein level came down. And we know homoicysty in is sort of an indirect marker that puts you at risk for heart disease and other complications. So the other thing is that the clinical trials with NMN and NR have been not entirely negative, but mostly negative. I would say the field that has been globally disappointed so far by what we've seen with these precursors. Now again I should hasten to say that I'm not saying that nobody should take them. If you're taking them and you're seeing good effect on your biology and your doctors supportive, I don't think there's going to be a lot of harm. But I think we can do better with the CITY thirty eight inhibitors. That's my prediction.
00:24:20
Speaker 1: Do you worry about any type of cancer development with anything that impacts NAD.
00:24:24
Speaker 3: There's been some evidence that actually some of the precursors might accelerate to growth. So this would be putting a subset of people who take these supplements who already harbor a cancer sell and already existing cancer. As I always say, people take a supplement with some degree of I would say carelessness. My argument is that supplements are not benign molecules. Some of them actually are powerful biologicals, and that none of them comes without a consequence. As you know as a physician, there are no drugs that doesn't have a side effect, and the question is to understand those side effects and then to mitigate the risk, and then to understand what you're looking for. For example, I work on an ady metabolism. If I had not worked on any metabolism with the deep understanding of all the biological consequences, I would never have looked at my homo system level. So this is where we are right now with many of these supplements that are touted in the aging field. Is there's some promise. And I should say also that n R and n MEN and animal models had remarkable effects. We published on some of those. I went into this field thinking this is going to be an amazing solution. It has been disappointing in clinical child not entirely, I should say, so there's still some hope that these these might be helpful under some unique conditions. But we just right at the beginning of this, and I think we need to understand that the whole process better and to really look for what the potential problems are.
00:25:57
Speaker 1: So let's talk about some of the buzzier topics that are going on in longevity right now. Rapam ice and an impact on longevity.
00:26:04
Speaker 3: Yes, Rapamisin is a great example. It's a small molecule drug. It's with isolated from a bacteria that came from Easter Island, which is in the local language called Rapa nui. Its target is a protein called Tor t R target of rapamcin. Not very original, but there's one that you cannot you cannot forget. Tor is a key molecule that regulates cell growth. Okay, So our cells can be in two different modes. They either fed or they're fasted. Okay, so when they're fed, they get energy, they activate growth, cell division, all this when they're fasting going to some like a bystandard mode. And tour is really a key regulator that gets activated when food is abundant. What happens is people have found out that when you suppressed TOUR with rapamycin, you actually induce a fasting like state. And we know that fasting, your calorie restriction is associated with longevity. People said Okay, they put the two together and say, if this jug is acting like a calorie restriction mimetic, maybe it is also going to increase lifespan just like calorie restriction, and so rapomizin. The most amazing thing is that the protein tour is conserved from yeast all the way to humans, and rapom icin seems to be working on this very important protein. And what's been shown is that in almost all animal species where it has been tested, rapromicin increases lifespan by twenty to thirty percent, including in mice, and including in mice that are kind of old. That was one of the study that got people really excited. If you take a mouse that's the equivalent of a sixty five year old, you can actually see a further increase in lifespan by twenty to thirty percent.
00:28:04
Speaker 1: Are you taking rapamycin No.
00:28:07
Speaker 3: I took it for a while. Essentially, I've taken pretty much everything that's in the book sort of a way to self experiment because of my position. I feel I want to be able to talk about all the things that I discussed in the aging field from a personal perspective. I took rapermicin for a couple of years. I stopped during the pandemic, and the reason was that rappermiicin is actually in approved molecules. It's the drug that exists in the market. It's called rap immune and it's used at high dose as an immunosuppressant. So if you get a kidney transplant and we want to make sure that your immune system does not reject your kidney, you go on rap am icin. At that time, I was worried about some immunosuppressive effect of the jug which are present even at the dose that are used in the aging field. Typically in the aging field you take a bigger dose, about six to eight milligram once a week, versus one to two milligram every day that the patients take for rejection suppression. I took it for a couple of years. I stopped during pandemic because I was worried. I think this is not the time to be immune or suppress when you have a deadly virus circulating. And then I never went back on it. One reason is that what I took ropomicin that didn't feel any different, and I never saw any difference in any of my numbers. My approach is to take a drug tested and then to see, okay, does it change anything in my biology that would be predictive of a positive effect, And I never saw anything, So it's an end of one experiment. The whole idea is to do a large scale clinical trials where we are randomizing let's say two hundred people, some one hundred will get a plus abo or one hundred will get rop amcin, and then we follow them for a period of time and we use all the biomarkets of aging that we have to try to see is there a signature that looks positive and promising in terms of lifespan and health span. And those trials are ongoing. An area that might be of interest to your audience today is colleague of mine at Columbia. You've seen Sue has conducted the clinical trials where she gave rapamycin and I believe it's pre menopausal women. These results are not published, but they are circulating. Everybody's talking about them, and she was able to show some signs that there might be a positive effect of rappamicin on ovariant function, which would mean that you could maybe delay menoclause or mitigate some of its effect.
00:30:39
Speaker 1: When you look at your numbers impacted by these different strategies. What are you looking at? I would assume lipids, inflammatory markers, but do you drill down on things like ink cells and such like this?
00:30:51
Speaker 3: Personally, I really go through your classical biological numbers. I'm always watching in terms of glucose metabolism, fasting insulin, hemoglobin A one CE, fasting blood sugar. These are really key variables that we know are predictive of human health. But also, as you mentioned, iflammat markers, high sensitivity CRP, IIL six, all of the lipids of course, the different types of T cells or link for it cells circulating in the blood, and so on. I go beyond your traditional sort of things that your doctor might measure to try to get a comprehensive picture.
00:31:30
Speaker 1: Let's talk about some other longevity strategies that are hot topics. I'd like to speak a little bit about Mett Foreman before moving into GLP ones great.
00:31:39
Speaker 3: Because I think those two are related. Let's step back for one second. I alluded to the fact that metabolism is really key to aging. Why do we know this? When I talked about Cynthia Kenyon early in the discussion, who identified some of the early genes that controlled aging. What was remarkable about her work is that many of the genes that she identified were actually part of a pathway. And that pathway is called insulin signaling. And so insulin is a key hormone that allows you to metabolize glucose. So when you're eating carbohydrate sugar, your body will respond by triggering insulin, and insulin is a growth hormone. It helps you to utilize glucose, and so this is central to metabolism. Now do I bring this up? So this is data that came out out of the Little Worm Sea elegance. Linda Partridge, another colleague in London, identified the same pathway in flies, and subsequently others identified the same pathway again in mice that are all controlling aging and metabolism of sugar via insulin. So that's one piece of evidence that suggests that the whole pathway is important. The second evidence is something called ITP, the Intervention Testing Program. This is a program that was set up by the NIH in Washington, and the idea is that if you are a scientist working in the field, and you have a drug or an intervention that you think will modulate aging. You can nominate your candidate, you can write a short a five page summary saying what is the evidence, and then they will test it at three different sides and mice. So they will give the drug to mice a large number of mice, larger than any individual scientists could actually do by themselves, and it's at independent site, so you eliminate all the variability of mouse colonies and so on. They've gone through seventy molecules, and I think out of this something like the order of eleven or twelve emerges longevity drugs. They seem to be increasing lifespan in mice. What's remarkable is a whole series of molecules have emerged out of this wrap of isin was one of them, is actually the best candidate to this day, but a whole series of other molecules that are also targeting insulin and glucose signaling emerge out of this. So this was the second line of evidence that paying attention to insulin and glucose is really key and understand aging and in the interventions that we're trying to generate. Now. Met Formine is an anti diabetes drug. What is diabetes is a disruption of that whole metabolism of glucose and insulin, and you can either have type one diabetes where you're losing the cells that are making insulin. This is a neutoimmune disease, so it's not related to aging. But you also have type two diabetes, which is the maturity onset type of diabetes, and we know this is a risk factor for accelerated aging. So there's so many lines of evidence that point to this pathway that people have been paying particular attention to. What are these drugs and can we actually redirect them in the aging process, And this is where metformine comes in. There are other drugs that are emerging in the same pathways that are really interesting. One of them is called a carbos. A carbos is another drug that also increase lifespan in the ITP and a carbos blocks the absorption of sugar in the intestine. It's an approved drug, you can take it. It has some side effects, some people have abdominal discomfort and so on. Another drug that has emerged are the so called sgilt to inhibitors, also anti diabetic drug. A good example is a drug that some of your audience might know called Jardians, very effective anti diabetes drug. It works completely differently. It forces your body to pee out the excess sugar that you might have in your blood. Okay, so it works at the level of the kidney, so completely different from a carbos or metformin, But it really helps with diabetes by blunting the high sugar level that you might have if your insulin does not function well. And what people have been observing is that SGILT two inhibitors appear to have global protective effect. They have cardioprotection, they have kidney protection, so they have protection that seems like something that's working globally. And so again agreeing with this model, the last player in this whole area is the GLP one drugs ozampic manjiro we go, vi zep bounds or the whole family of drugs, which by the way, are originally designed as anti diabetes drug that what's really interesting is they do protect against type two diabetes, but they also seem to be having some of these global effects that we are expecting from anti aging drug They protect against heart disease, they protect against cancer. That was the latest thing that we've seen. So there's a lot of emerging evidence that these drugs might be more than just anti diabetes and antiobesity drug, that they might have global anti aging effect.
00:37:03
Speaker 1: You've taken GLP once for longevity strategy. Correct.
00:37:06
Speaker 3: Yeah again, And I want to make sure that this does not sound like me advocating about them. This is part of my self experimenting regimen. Yes, I have taken them and I am still taking them at low dose. The reason I started taking them is that going back to glucose and insulin, what we see as part of the aging process is the system degrades. That is, you need more and more insulin to have the same lowering effect on your blood sugar. So in most people, as you age, if your doctor measures your fasting glucose, you will see over a period of years your fasting glucose rising up slowly. I have a family history of type two diabetes, and my genetic analysis, my genome analysis identifies type two diabetes as one of my major risk factors, and so I went to see my doctor. I have a doctor with my work closely is sort of my you know, I guess it prevents me from doing anything stupid and sort of like the voice of reason. And I argued with him that I could see my fasting blood sugger rising, and when it got to ninety eight, which is short of one hundred. At one hundred you are defined as pre diabetic. My argument to him was, I'm on a trajectory to become pre diabetic in a couple of years based on the curve, and I want to try to prevent this, and so I went on a GLP one agonist and it was actually truly remarkable because within a month my fasting blood trigger was back down to eighty five. My fasting insulin, which is another indication of how incidin sensitive or incident resistant you are, went down from eight down to two, which is the lowest level in which you can be. My aboglomine one C, which is a representation of your average glucose level, went down from five point seven against close to pre diabetic, down to five point two. For me, this was a good example of an intervention that really had all of the desired and predicted effect. And I've been now in it's since I should say also, these are lowdos. I take two point five metigram of tears appetite, which is the munjyro. That's the starting dose that most patient would go on and I still see these beneficial effects. I'm not the only one to see this. By the way, this is seen in many patients. One argument, and an important question is are these effect independent of weight loss or is the weight loss always the driver? In my case, I lost probably three or four pounds, so this was not a major weight loss, and I saw these dramatic effects. I would argue, based on en of one and other anecdotal evidence from talking to other colleagues, that these drugs are likely to have effects that go beyond weight loss.
00:39:55
Speaker 1: You pay attention to body camp, you strength train, checking your body camp and making sure muscle mass day is intact.
00:40:03
Speaker 3: That's an important, very important aspect. So you know, there's been a lot of noise about the GLP one agonists in terms of they do inde a loss of muscle mass. I should say that many of these observations have been made in patients who underwent massive weight loss. Okay, if you're losing weight your body, you will not lose only the fat. You will lose both muscle and fat. There was an interesting study that compared the relative amount of weight of muscle mass that you had on GLP agonists versus gastric bypass for example, which is another intervention that also induces massive weight loss and low and behold, there was nothing special about the GLP one agonist. They induce muscle loss, but to the same degree as a gastric bypass. So there's a lot of people have argued with me, you're gonna lose your muscle mass. Well, I have not lost any muscle mass, but I agree with you. I watch my protein INTAKEE which is a big driver of muscle mass maintenance, and also I do strength training, and so between these two I can tell people all of the effects that I've seen have been independent of any muscle loss. The last point I want to make is I believe, and this is a personal opinion, that the way we're using these drugs is probably not optimal at this point. And I would argue that no one should lose thirty pounds in six months. That probably indicates, in my opinion, that we're inducing two rapid weight loss in people. My prediction is that in the future we probably will change the way we use these drugs and induce much slower weight loss, for example, thirty or forty pounds over a two year period. If you want to have something that's going to be more sustainable and mitigate some of the effects that we're discussing, such as muscle loss. I think doing it much more slowly at a lower dose is probably going to be the way to go.
00:41:56
Speaker 1: Any concerns about the ocular side effects of the golp ones.
00:42:00
Speaker 3: Yes, there's been a number of instances where people have developed these acute eye problems. I would say this is a very small number of people who were at risk for these conditions already and this might have been accelerated by the drugs. It's still early.
00:42:19
Speaker 1: Still to come. What can we do about chronic low grade inflammation sometimes referred to as inflammating plus some super simple tips that you can incorporate into your everyday routines. Back in a minute, I want to ask a little bit about the role of inflammation and longevity strategies and aging what we call, I guess inflammating, right, Can you just break that down for us a little bit and tell us about the importance of inflammation and actually what it is.
00:42:54
Speaker 3: Let's start with what acute inflammation is. Acute inflammation is a protective response that our body has to respond to damage, and damage can be a cut, a burn, or an infection. If you burn yourself on your skin, within a few few minutes, the area will get red, it will be painful, and it will get swollen. So these are the three hallmarks of inflammation. So this inflammation means immune cells are coming into the side of the lesion and it will start repairing. So inflammation is actually is a protective and repair mechanism. Now, the type of inflammation that I describe here is acute inflammation and result inflammation. What happens during aging is different. What happens during aging is the damage accumulates, it does not repair completely, and so this persistence of the damage leads to a chronic activation of the same mechanism inflammation. And so this is what people refer to as inflammating, and it happens in the whole body. When it becomes chronic, it actually by itself can cause some damage. And so this is why there's been so much interest in understanding what inflammating is. There is a lot of work that's ongoing and actually novel drugs that are being tested that are trying to say what would happen if we would suppress inflammating. An example of drugs that are currently in development are the so called inhibitors, and these drugs appear to be having protective effect and they are right now being tested in obesity. It turns out that obesity itself is pro inflammatory for reasons that are not totally clear, but obesity itself causes increased inflammation and acceted aging, and so there's been a lot of interest in saying can we block this, And these LP three inhibitors right now are being explored in obesity. It turns out that inflammation is a shared pathway between many of what we call the chronic disease of aging, and I'll mention them heart attack, stroke, cancer, many forms of cancer, neurodegeneration, Parkinson's, Alzheimer. Many of these diseases have a very strong inflammatory component. And so the whole idea is if we can block the inflammation, maybe we will block all of these diseases together. That's the premise of the whole aging field.
00:45:23
Speaker 1: Let's talk about estrogen as a longevity strategy. Is early institution of estrogen a longevity strategy for women?
00:45:32
Speaker 3: I believe it is. If you look at aging in women pre minopause, women age slower than men, partially or probably in large part due to the protective effect of estrogen. Now, at menopause, that whole system goes away, the ovaries stops making estrogen, and what we see is postmenopause women actually show accelerated aging and they show accelerated propensity for all of these diseases that I just mentioned, heart attack and stoke. And actually the sort of the model that many of us have in our head is that men suffer mostly from heart attack, but that's not true a postmenoposal, women suffer for a lot of heart attacks. Alzheimer's women are more at risk than men, So you see women living longer but living more sick than men. In general, most women, and of course this is not my recommendation, this is sort of generally with a field would probably benefit from homeown or replacement therapy. And I would say the sooner the better in terms of blocking some of these effects.
00:46:40
Speaker 1: Yeah, because as estrogen goes down, I think that an RP three and flammism actually goes up. And I think it's going to take science actually and longevity strategies to really upfront estrogen for women again, because if you look at the trials, they're all observational right now. But I think if we can prove the science. I think we can help move that forward a little bit. I'm hopeful of that. What do you recommend to the women in your life to protect their longevity? For healthy longevity?
00:47:08
Speaker 3: As I mentioned about fifty percent of launche is genetics. So as my friend near Barzilai would say, choose your parents, well, that number one.
00:47:18
Speaker 1: Your destiny exactly.
00:47:20
Speaker 3: The good news is if someone in your family is a centenarian, and if you have a first degree relative that's a centeneieri, and that probably means you're carrying some protective genes. That's a good news. But for most of us, we don't have this, and we cannot change your genetic material. At least we can, but it's not being done for aging right now. It comes down to lifestyle. The cutting edge of the science is that in the future, I suspect we will have gene therapies that will really address your genetic deficiencies, that correct and make you more like a centenarian. But for most of us and today, and my argument is that this is what we know today that you can do it, it will work. It comes down to your lifestyle factors. When I speak about lifestyle, I speak about nutrition, physical activity, sleep, stress, medigay, and most important social connections. I think about those as bank accounts. Just like an investment, you want to start early. The early the better, I would say. You know, you start aging at age thirty or twenty five to thirty, and the earlier you invest, the bigger the benefits. That's number one. Number two, you want to diversify, just like when you do investment. Each of these bank accounts is actually works somewhat independently. You know. I talk to a lot of male friends who tell me what I exercise so much. I can eat anything I want and I'll have another French fries. I'm from Belgium, so I'm very partial to French fries. They're not very good for you, but they're you know, they're good to eat with friends, and so you have to mitigate the healthy effect and being social. The same goes for alcohol. It's not good for you, no safe amount of alcohol, but we drink it with friends, and therefore we reap all the benefits of the social interaction. Think about each of these bank accounts as areas that I focus on. And one tendency that some people have it says, well, I don't like to exercise. I said, well, you can walk, and the data, for example, says that walking thirty minutes a day has a enormous effect on your health. That's fifteen minutes in the morning, fifteen minutes at night. The science is moving rapidly and helping us to identify what is the most healthy lifestyle to maximize not only your lifespan, but especially your health span.
00:49:44
Speaker 1: Nutrition. Do you recommend intermittent fasting? Yes or no? If somebody can tolerate it. How much protein, protein heavy?
00:49:51
Speaker 3: More?
00:49:51
Speaker 1: Quito? What do you think is the best longevity strategy with nutrition.
00:49:55
Speaker 3: I'm not into what I call the fad diet. Many of them are generated essentially to sell books. You know, none of them has been truly documented to be superior to the other. There's one diet that stands out, what we refer to as the MIDI tony and diet, which is lean proteins, a lot of vegetables, nothing in excess, limiting alcohol and so on. You know, as Michael Polland has said, you know, eating only what your grandmother would recognize as food. I would say, if you look at your store, shop on the outside of the store, which is where all of the non processed food. Your meat, your dairy, your vegetables, everything that's the insight that comes in a box is processed. Good example of this, you know, standard American diet people will eat cereal for breakfast. Cereal essentially is a bowl of sugar and you mix this with a glass of orange juice and now you have two bowls of sugar. Doesn't mean that you cannot eat a chip from time to time, but if you're eating potato chips every day, I can guarantee you it's not going to help your health. We live, unfortunately, in a society that has completely distorted our taste. You know, for example, there's good value in fermented food. Yogurt, kfeer, kombucha, kimchi, sauerkraut are all fermented food. They play a key role in gut health. And I argue to people that's one thing that you just try to do every day, and I have four to five servings of these fermented food every day will help your gut health. The reason I brought up to yogurt is I used to eat these fruit yogurt and you're sweet. Because of everything that I had learned, I forced myself to stay away from them. And to start eating regular yogurt. And at first your reaction is, well, it doesn't taste good. But with time you can re educate your palate to actually enjoy food that is not saturated with sugar. It's what I call corrupted food. It distorts your palet. Regular yogurt, with its acidity, actually tastes frankly right, No, I like it better because I've sort of forced myself to, you know, learn how to taste things differently.
00:52:13
Speaker 1: Yeah, when you stop eating sugar, you don't crave it the same way.
00:52:17
Speaker 3: That's one thing. Sugar is an incredible addictive potential. The more you eat, the more you want, and your taste butts are completely I would say corrupted. Over the years, I have changed my diet progressively to try to I'm not perfect, you know, I will have French fries from time to time, so I would say avoid the fads of you know, this diet is going to solve everything. Keto diet. I was on a Kitto diet for three years, but it helped me lose some weight. Barely can eat any fruits on the Kto diet, So this was something that I felt was not pleasant or necessarily healthy.
00:52:50
Speaker 1: Talk about exercise. But what do you do in terms of exercise?
00:52:53
Speaker 3: Yeah, so first let me step back and tell the different categories of sports. One would be what you refer to a zone two. That would be walking, jogging, swimming. So this is this type of exercise that you can sustain for an hour that were you still able to maintain a conversation, but right at the edge. So that would be your zone to training. That's none to be important for cardio pulmontary function. It makes your heart strong, it will help a little bit of muscle function. Then you have what I call high intensity interval training or HIIT. This is the same type of exercise, but where you're pushing to your limit. Obviously it's not something for someone who's never exercised to start doing. I would say start by walking thirty minutes a day, and then once you're able to do this, if you want to get maximum benefit, add one or two minutes of these very intense bouts sprinting or something that you push yourself until the point that you cannot breath and you have to stop. So this has a whole series of other advantage. It will increase something that we call your VO two max, your maximum ability to extract oxygen out of an exercise, and it has been shown to be a very strongt of your life expectancy. Okay, so if you don't do anything and you start walking, wonderful. If you want to reach the next stage, you'll have to push yourself within reason, and if you have a heart condition, with medical supervision, but push yourself to the point where exercise becomes uncomfortable and where you're sweating and where you are out of breath. These would be the two key fundamentals. Then you have strength exercise, which is where you are increasing the load on your joints and on your muscle. Good example of what I do. I have a kettle bell at home and so every morning when I get up, I'll do fifteen minutes of kettle bell and you can do them at many different weights, five, ten, twenty thirty pounds. And if you go on Instagram, you will find so many kettlebells, routine workouts exactly and I loved I loved those. I was just traveling for a month in Europe and I did not have a gym, and I bought a kettle bell wh I arrived there. It cost twenty five dollars. It was in the back of my rental car. So every morning I had a minimal exercise that I could do with the schedule battle and this, along with the walking, allowed me to maintain a routine and to still try to stay on top of it. Then there's two more categories. One is flexibility. As we age, we tend to become stiff and this eventually the stiffness can become really sort of severely hampering your mobility, and then it becomes a vicious circle. And the last one is balance, which becomes especially critical as we age. You hear all the time the stories of eighty year old falls, breaks his or her hip and within a month they pass away because they get into the hospital they get an infection. I would say maintaining a strong balance is actually something that you can work. I tell people, you know, every morning, I brush my teeth on my left leg in the morning and on the right leg at night, and that's my balancing exercise. Every day. I do ask other exercise that trigger your balance. Yoga is great for this. You want to know what my sort of go to exercise on an almost daily basis is I take classes of hot pilatis and for me, this exercise in the heat brings two benefits. One the hot pilartis has some cardio aspects, but it has flexibility, it has core, it has strength, and it has pretty much the whole package. Frankly, it also makes me feel incredibly good mentally. And this is one of the beauties of exercise. You know, it will help you maintain brain function.
00:56:48
Speaker 1: It's why I'm in the gym every morning lifting weights.
00:56:51
Speaker 3: Good good.
00:56:52
Speaker 1: Is there any one biologic clock that's commercially available that people should get that you recommend. My impression is that they all tell you something a little different, and maybe you look at them over longitudinally. Choose one and look at it longitudinally over time. But what is your opinion on the commercially available clocks that somebody may be interested in going out and purchasing.
00:57:12
Speaker 3: There are so many of them, and I've tested most of them. My age varies between twenty five and seventy two. Yeah, what do I do with this? So many of the clocks are more like an autometer on your car. They tell you how many miles you've traveled. There's one that is the equivalent of a speedometer. It tells you how fast you're aging at any given point. It's called dinnerdin Pace. It's sold by a company called True Diagnostic. It's not cheap. This is the one that I follow every six month and I try to optimize it.
00:57:46
Speaker 1: What's on the horizon, What do you see for the space in the next five, ten to fifty years, and what do you hope for this space?
00:57:53
Speaker 3: So two things. The first thing is that the science of aging is accelerating right now. It's going very quickly. AI just put everything that we're doing on steroids. I mean, the discovery is coming so fast. As a leader of the Buck Institute, I could spend my whole time just following the literature and what's happening every week. So I expect that the next five to ten to twenty years are going to be extraordinary in terms of what we discover. Now, I tell everyone, the only thing that's demonstrated today are the lifestyle factors. There are no supplements and no drugs that are proven in a definitive manner the way we want to see a scientist to increase your lifespan. So resist the temptation to go run to the next Instagram fad. And so I'm going to take an AD or NMN. I'm going to solve everything in terms of aging. Avoid the supplements. So if you're exercising and then you want to take a supplement on top of it, fine, I don't know. If you are on LinkedIn, it's Eric Verdin, MD, and I post every single day lifestyle facts and things that happen in the longevity field. This really actually resonates a lot of people because the public is sort of lost in between what I call instagram medice and true longevity signs. So longevity science is focusing right now two things. One is, of all these lifestyle factors, what is the optimal proportion? You know, we talked about all these different forms of exercise, how much strength training should you do at what age? There's an important dimension there, which is the we're all different. You have a different body composition that I do your women. I'm a man, but even if I compare two different men, different people's physiology are different. You know, there's some things that are beneficial for everybody, like walking thirty minutes a day, but there are some regiments that can be tailored to individuals. This is the whole idea of precision medicine or precision wellness, that we are developing the tools so called biomarkers of aging that will in the future allow me to tell you I think your routine is optimized, you're doing as well as you can, or I would increase strength training, and then I would see you again a month later and I would see of that marker and this market changed in the right direction. And I want to bring up the wearables. Since you're in the gym every day, I suspect you have one.
01:00:17
Speaker 1: A lot of them. Okay, all right, experiment.
01:00:21
Speaker 3: Wonderful walk. I would say that everyone should wear one and become sort of more educated about their own biology. You know, a lot of people know a lot more about their cars and respect their cars a lot more than they do their own bodies. Imagine having a dashboard when you start your car, tells you what your oil pressure is, your everything. There's a little light going up, You're going to go see the garage. Most people don't have a dashboard for their own health. And I think the wearables is the first step in this direction. And my prediction is twenty years from now, every doctor will have all of their patients wearable data and they will be able to identify early signatures of problems and so on. You cannot change something that you cannot measure, and this is really one area in which the aging fields moving. That's Number one. Optimize your lifestyle factors. Do it with a coach, do it with a wearable, do it with a doctor the specializes in longevity. Number two, we are all different. Some of us are much more at risk for etceteraly aging than others. And medicines are coming that are going to be targeting the aging pathway. By the way, we might already have them. The GLP one agonist, I would say in my book, are sort of have many of the signatures of what I think will be anti aging medicine, but they could be others as GILT two inhibitors. The question is going to be at some point who gets those? Does everyone go on these medicine. I'm experimenting with them, but I'm a scientist and not a good example of what everybody should do. But there could be a time in the future where many of us will be on some really unique interventions that are targeting our own frailty points. And none of us is perfect. Everybody carries some unique polymorphism in their dnated that pretty poses them to some unique conditions. So I think that's the stage it's going to happen. I would say in the next ten years is that you're going to hear more and more of people saying my longevity doctor saw this and he recommended that I take this now. This doesn't mean that every forty year old is going to go on met forman frankly, I get horrified. I've had like a thirty year old man who came to see me and asked me whether you should go on met forming and ask them why would you do this? He said, well, because it's a longevity jug. I said, well, do you know what the side effect of met forming is is, well, it would suppress your testosterone. So if you're ready for this at age thirty, you know, good luck. So that's the understanding that there's no free lunch. And actually longevity comes mostly with a lot of hard work, which is just paying attention to your health and really building lifelong habits that will allow you to live better, longer. And you know, someone asked me what is the best form of exercise for longevity, and my answer is it's the one that you do. There's no perfect rules, but if you can develop sustainable habits, I think that's the key.
01:03:18
Speaker 1: The science of longevity is no longer confined to animal research and hail Mary's. The findings emerging are beginning to translate into genuinely actionable guidance for how we live, eat, move and age. Just as our physical bodies are not fixed, the same goes for aging. It's not a case of biologic destiny, but a process, one that is influenced by the choices we make, the environments we inhabit, and increasingly the interventions that science and medicine will soon make available to us. If this conversation sparks something in you, here are a few ways to go deeper follow the science directly. The Buck Institute publishes accessible research updates at Buckinstitute dot org, and doctor Verdon is active on social media, sharing the latest bindings in plain language on Instagram, LinkedIn, and substact to name a few. By the way, I also have a substack called the Female Longevity Project, which we'll link to in the show notes, as well as on Instagram at pointer health Plus. We regularly publish on longevity science at content dot Atria dot org. As for what to do. First, start with what we already know works. Resistance training, consistent sleep, reducing ultraprocessed foods, managing chronic stress, and staying metabolically healthy are not simply wellness cliches. They are the interventions with the strongest existing evidence base for extending health span. Get your annual blood work done. Ask your doctor about inflammatory markers like high sensitivity. See reactive protein, fasting, insulin, hemoglobin A one C, and a DEXAS scan for bone and muscle composition metrics that longevity focused clinicians consider essential baselines. Find a longevity informed physician. The field of longevity medicine is growing rapidly, and practitioners trained in this framework think about prevention and optimization differently than traditional disease focused medicine. The science is moving fast. What we understand about cellular aging, inflammation, and metabolic health today is already dramatically more sophisticated than it was five years ago, and the next decade promises even more. De Coding Women's Health is a production of Pushkin Industries and the Atria Health and Research Institute. This episode was produced by Kalalia. It was edited by Amy Gaines McQuaid. Mastering by Sarah Bugare. Our executive producer is Alexander Garreton. Our theme song was composed by Hannas Brown. Concept and creative development by Shaban O'Connor. Special thanks to Vicky Merrick, Alan Tish, David Saltzman, Doctor David Dodick, Sarah Nix, Jacob Goldstein, Leah Rose, Jordan McMillan, Morgan Ratner, Owen Miller, Eric Sandler, and Greta Cohne. I'm doctor Elizabeth Pointer. Thanks for listening and until next time.