What Actually Extends Your Lifespan (According to Longevity Science)

I think doing nothing for people is harming them. We should be trying to really focus on people's health throughout their life course, not only after they get some ICD code because once they get really sick, it's really hard to fix them. Not only is it about preventing disease, it's about optimizing performance.

Dr. Brian Kennedy holds a PhD in biology from MIT and is currently a distinguished professor of biochemistry and physiology at the National University of Singapore where he directs the Center for Healthy Longevity. He has published over 240 scientific manuscripts and his current work spans biological age testing with lineage human trials of rapamyasin and translating longevity science into real interventions for real people.

When it comes to taking supplements, it's really about finding the right combinations that work for you. And there isn't a one-sizefits-all for activating autophagy. One of the best markers is whether you're in ketogenesis or not. And you can measure that. That's different for different people. For some people, it's 16 hours or more of fasting. Other people can do 1212 and they can get activate ketogenesis.

How much protein do you think you know is optimal?

I think a lot depends on how much you exercise. High carb, low protein is associated with longevity, not high protein, low carb. The second thing is that what we're really defining is the optimal diet for sedentary animals, but a lot of humans are sedentary. And so if you're eating a lot of protein and you have a lot of circulating amino acids and you're not using those, then that's a risk factor for cardiovascular disease and kidney disease.

Okay, today I am so excited about our guest. He has come a very far way. Um, and he is Dr. Brian Kennedy. He is one of the most respected figures in the science of aging. He has spent his entire career dedicated to answering the questions of why we age and what we can do about it. Dr. Brian Kennedy holds a PhD in biology from MIT and is currently a distinguished professor of biochemistry and physiology at the National University of Singapore, where he directs both the Center for Healthy Longevity and the Asian Center for Reproductive Longevity and Equality. Before that, he served as president and CEO of the Buck Institute for Aging, the world's first independent research institution focused entirely on aging. He has published over 240 scientific manuscripts and his current work spans biological age testing with lineage human trials of rapamyosin and translating longevity science into real interventions for real people. Welcome to the podcast.

It's my pleasure to be here. It's great.

What I mean I'm so excited to chat with you. You've just I mean you've dedicated your whole life to this essentially, right? Well, tell us a little bit about your backstory. Like you got started and then went into what?

Yeah, you know, I it was a little bit unprepared, but when I went to graduate school at MIT, I wanted to do something different and out there in terms of research and um the opportunity to study aging was something that, you know, people didn't I couldn't understand it. You know, we had something that affects everybody on Earth and very few people were doing research on it. It was just thought of as a natural process and not much you can do about it.

Uh but we decided to start working in yeast cells and this was in Lin Garenti's lab and um not because we thought what we would learn in yeast cells would apply to humans necessarily but we thought a simple cell system might be a good way to understand the principles of aging and then we could apply those principles. Um, turns out that we found the certuin pathway, we found the to pathway using those simple yeast cells. And and what we learned is that there's remarkable conservation of pathways that govern aging across a wide range of species. And that's important because it means you can study animal models and even invertebrate models to uh understand the aging process.

And mTor and certuins for anyone that's listening that doesn't know what that is would you give give a little bit of description?

So certuins are family of protein diaetylaces and uh they've been linked to aging so if you have increased cert1 or cert activity it extends health span and lifespan in pre-clinical models even up to mice. And there are a lot of uh natural products that are thought to activate those diaetylaces and people are taking those like NAD precursors for example. Um and the mTor pathway is really intimately linked to I think calorie restriction. It's a kinase act pathway that when it gets activated by nutrients it tells the cells to grow and divide and when you starve cells or reduce their nutrient exposure uh it turns down those proliferation pathways and turns up stress response pathways like autophagy. And that protects the cells. So uh drugs like rapamy that inhibit the mtor pathway are very promising in terms of longevity.

Is there a way to um measure autophagy or how deep you are into autophagy?

I mean there are a lot of molecular ways to do it. It's I'm not aware of any sort of uh tests commercially that are available. But if you you know if I take your cells I can measure it.

Yeah. Yeah. I'm always I'm always wondering because you know like many people I'm always wanting to cycle in and out of that but then I don't know how to actually measure how deep I am into it and it seems a bit you know there's different lines of thought like you know how long it takes exactly how long do you feel it takes in a human I'm assuming it's bio individual right because some people could have more stored?

All of these things are personal you know I think we'll probably come to this later but I think when it comes to taking supplements you know it's really about finding the right combinations that work for you and there isn't a one size fits all. I think for activating autophagy, one of the one of the best markers is whether you're in ketogenesis or not. And you can you can measure that. Um

The uh that's different for different people. For some people, it's uh 16 hours or more of fasting. Other people can do 1212 and they can get activate ketogenesis. Also, there's some uh uh concerns that if you do too much fasting. So again, that's a place where you need to find the right the right model for you and and I realize it's easy to say that and hard to do that for the average person. So that's sort of the challenge of the field right now. I think we know a lot about aging and we know a lot of things we can do to slow the aging process, but applying that at the individual level right now is still as much research as it is clinical practice.

So yeah. Um going back to the key maybe measuring your ketones because that's something I can easily do here. Is there like a threshold like are there is it X amount? Do we want to be at like four um you know in the ketone measurement to be an autophagy or if you just have any ketones measurable?

I I think any ketones is a good sign because it's not easy to get into ketogenesis for most people. Uh

And go kind of right in by?

Yeah. Yeah. I'm guessing you're you know how to do it. But

Um but yeah, I think anything is a good sign there. And you know, also I think how you get to ke ketogenesis is really important. Like I'm not supportive of these heavy ketogenic diets particularly because I think they're hard to maintain and you know they will cause weight loss and they will cause ketogenesis. Uh but they're hard to maintain and then when people go off of them they often recover their weight or even more. Um, so, you know, I I think fasting is a really good way to get to ketogenesis because if you do 16-hour fasts and that's healthy for you, you can achieve that and still eat a relatively normal balanced diet. I I kind of a boring guy. I recommend balancing macronutrients.

I mean, I I totally agree. Are you in the line of thought of like the Mediterranean diet? Is that kind of what you're thinking?

I think that's healthy. You know, I one of the things I did that really helped me is that I started monitoring my calorie intake. Because I thought I knew how many calories were in different foods and I sort of did, but there were some big surprises, too. So, uh, now I'm more careful about that. I try to get to the right number of calories per day. I don't do fasting on a regular basis because I'm traveling all the time. It makes it hard to do but yeah.

Um I do try to get about normal calorie intake and get enough protein in my diet and and uh watching what I eat helps a lot there.

Yeah. Well, how do you define fasting? Like how many hours would you say constitutes a fast?

Well, you know, for personally when I when I try to do it, I try to eat one meal a day like in the evening. So I will not strictly on a water diet but pretty close in the during the day and then during the evening I have one meal of whatever I want. Um

Uh so this works for me. I think a lot of these things are about sustainability, right?

You have to figure out what works for you. Now you might argue that while eating your big meal in the evening is a bad idea.

I was going to ask I was like like how close to bed? And there's some truth to that probably, but it works for my lifestyle. And uh I I think for the majority of the population, trying to find sustainable changes you can make, even if they're not huge changes, sustainable changes that you can make that fit your lifestyle is a good place to start.

Yeah, I agree. Well, going back since you mentioned it to the it's like the great protein debate right now, right? We have some individuals recommending you know one pound or more per pound of body weight. Then we obviously also know as you mentioned the mTor activation versus autophagy. Where do you land on that? How much protein do you think you know is optimal?

I think a lot depends on how much you exercise and how much you're how much resistance training you're doing whether you're using the protein or not because you know we know first of all that um in animal models you know we if you look at isocaloric diets for animals almost any animal they even did this in wasps I don't know who did the study in wasps but also in mice and other the the what you find is that high carb low protein is associated with longevity not high protein low carb. Now, there's some caveats to that. The first is that it's complex carbs, but you're giving the animals, not simple sugars necessarily.

Um so be like sweet potatoes, like kind of vegetable based.

It's a it's a formulated diet, but yeah, it's it's more complex carbs. The second thing is that um really, you know, I think that the um it these animals are sedentary. I mean, if you take a mouse, you know, and it's living in a cage in the lab out in the wild, it's running kilometers a day. In the cage, it's not moving as much. So,

What we're really defining is the optimal diet for sedentary animals. And but a lot of humans are sedentary.

Yeah.

And so, if you're eating a lot of protein and you have a lot of circulating amino acids, uh, and you're not using those, then that's a risk factor for cardiovascular disease and other things. So, and kidney disease. So, I think that balancing your protein intake to your usage is really important. And for healthy individuals, one way to look at that is to measure your nitrogen and your urine.

Um, if that nitrogen is really high, now it can be high because of pathology and other problems, but for a healthy person, if it's high, I think one thing it's telling you is you're probably eating too much amino acids for what you're using. And so I think and that comes back to one of the things I tell people is that taking things doing things you know interventions are great trying Hbot all these things are great measure measure measure you need to be measuring how your body's changing uh and uh the more you're measuring how you're changing the better you'll understand what works for you and things like blood ura nitrogen is a good example of of that it's a simple thing to measure and and uh gives you an idea about your diet.

Yeah, I love that. I mean, it also kind of validates what I'm doing personally is days that I'm having intense exercise training, I'm increasing my protein and then I think that makes sense. I'm down reggulating it on days um that I'm not. So,

Well, I want to kind of like take a step back and just talk about aging as, you know, a whole um there's really no one better to chat about this with, but um I mean, from what I understand, we went from having the nine hallmarks of aging. You, I believe, called them the pillars of aging, right? Um, and then we went to 12 and now we're at like 14.

Pretty soon it's going to be 20,000.

I mean, so what are your what are your current thoughts on hallmarks of aging? Like what are the common threads throughout them? What do you think we've got right? What might we need to work more on?

Well, even though I had a big role in writing that pillars paper, I've always been a little bit of a skeptic about this because, you know, I think we're we're identifying these pillars and hallmarks and certainly those are pathways that are related to aging and they are modified when you animals live longer. And so I I agree with all of that, but I think what it misses is is the systemic nature of aging. Really I think your body is interacting communicating different cells and tissues are communicating with each other and trying to keep you healthy. Uh so you have this like homeostasis in your body. You respond to things that are happening and you maintain your health and function.

Uh and but over time there's damage that's happening. There's stochastic events that are happening. You're maybe you're not living a great lifestyle and that system gets starts to break down.

And when that system breaks down, then you're susceptible to disease. And depending on your individual organ aging and your genetics and your lifestyle, you might get one type of disease or another. But I think really for healthy longevity, we're looking at maintaining that homeostasis. And so, you know, the interventions that extend lifespan like inhibiting mTor, they don't hit one hallmark or one pillar of aging. They affect all of them because they're maintaining the homeostasis in the body. And I and I think that that systemic component is what we should be thinking about. Uh the challenge with that is that it's easy to say what I just said, but it's hard to explain what that means. And um it's easier to to target different pathways and say this is what we need to do. But I'm not sure that fixing one pathway at a time is going to get us to immortality. I I think that we need to think more about the the body as a whole.

Do you think that immortality is possible?

Um, I don't know. Well, I mean, let's say not aging. Is not aging possible because eventually we're going to hit get hit by a bus or something. But

Yeah. Yeah, that's true.

But, um, I I think it's unclear at this point. Um, it's certainly no data that I know of that supports that. Um, I think let me take a step back. Uh, the qu here's another question. Is it possible to extend maximum lifespan?

I'm very confident that the interventions that we're trying right now, some of them are going to extend median life expectancy. They're going to extend health span and probably they're going to square the curve. They're going to get people closer to their maximum lifespan. Whether any of those interventions extend maximum lifespan or not is an open question. Now some of them do in animal models but if you look at the you know the human data analysis people like Peter Fedichev at Jerro are doing uh they might suggest that they're not going to affect maximum lifespan in humans and and that means we might have to think completely differently about how to get to 150 or longer and I think that's an open question in the field right now. It's really exciting research area ultimately I think it's possible but I'm not sure that the path we're on right now is going to get us there.

Interesting. And would you would you define the path that we're on right now as targeting the individual hallmarks of aging?

Uh that and also just I you know I look most of 90% of my research until recently was in animal models. Uh I've stopped torturing animals and now I'm torturing humans. We don't torture either. Don't worry. It's a joke. But uh um the uh all of that reliance on animal models identifies pathways that extend lifespan in animals. And certainly some of those pathways are conserved with humans. However, there may be key features of aging that are different in short-lived animals than in long lived animals. And uh we started a field uh called gerysics in the last couple years. Um which sort of brings the theoretical physicist into the gerontology research because ultimately I think if we're going to understand aging, we need to be able to write mathematical equations that define it. And that brings in you know concepts like entropy which is a complicated concept but you know it allows you to think about aging in a different way and it suggests that maybe if you really want to dramatically impact aging you have to look at different kinds of interventions. So

Yeah can you define entropy for anyone that's listening?

Yeah entropy is like a second law of thermodynamics. It's an increase in uh disorder of any system that over time and there are like 20 different kinds of entropy that are applied to different areas. But when you think about you, you know, as you're aging, you know, you are getting more disordered. You know, if you look at DNA methylation, for instance, you can see that, you know, it's highly regulated in a in young cells, but then it slowly breaks down over time. And so, um, that's happening in all your different systems and and uh um how to change that process is a at a conceptual level. It's a different way of thinking.

Yeah. Because I suppose a question would be is it is it just the let's say damage over time or is it more of a programmed you know um decline.

Yeah, I I think the the question of programmed aging is interesting. I I I don't tend to think of aging as being programmed. I think of health as being programmed. Uh and so to me that's a breakdown over time. Now there are models that suggest that aging is programmed and is part of our you know our evolutionary uh selection but um I haven't seen compelling data for that. So

Out of all the hallmarks of aging um you know the 12 that we have now are there you know one to three that you think are probably where we need to be focusing most of our energy.

Yeah, I I'm really focused on inflammaging and the increases in sterile chronic inflammation that are happening uh in individuals over time. I think that you can define increased inflammation in almost any process of aging. So, it's not not really the field I worked on my whole career, but I think it's just emerging every time we develop biomarkers of aging or we identify new drugs that target aging that are anti-inflammatory. And I think that uh that's something we need to focus on more. Now, it may be that chronic inflammation is something that's happening relatively late in the aging process. It may not be the early defining factors that are driving aging, but I think it's compelling that inflammation is touching on so many different components.

Um I I like to think a lot about adult stem cells in the body. I mean all of your tissues have stem cells that can replenish at different levels your your your tissues and they decline with function with aging. I think that's heavily linked to the mtor pathway and one of the things that uh reducing mtor uh signaling is doing is allowing adult stem cells to function later in life. So

You know and again that's very connected to proteostasis and you know rapamy is anti-inflammatory and so it gets really hard to like pull out one thing or another but those are two that that I think about a lot.

But isn't it like I mean it so we feel like suppressing the mtor could be really helpful but we also want to have muscle mass right which it's so it's like such a balance here and how do we achieve that?

Well, I think it's nuanced, right? I think what's what's happening with mTor is more complex. It's not just about turning it up or turning it down. This is a pathway that needs to be activated. For instance, when you do heavy exercise, you activate mTor in your skeletal muscle.

Uh when you have an infection, you activate mTor in your immune system. When you cut your skin, you activate mTor in your skin.

And it's there for a purpose. Um

The problem and when you're young though, you you can turn it off when you don't need it. I think that's the key thing. And as you get older, the data suggests that you can't turn this pathway back off.

And so mtor's on all the time. And so I think what's happening with something like rapamy if it's dosed right is it restores that dynamic range you have when you're young. You can still turn it on when you need to, but you can turn it off when you when you don't need it. And that's what's good for aging.

Now I noticed, you know, I've taken periodic. I'm not taking it now, but I've taken rapamy intermittently in the past. One of the things I do notice is that I feel like my exercise is not as good in the 24 hours or so after I take it because I I take it once a week.

Uh but then I feel like over a couple days my exercise performance is very good. So there may be some immediate effects of taking it that uh that's a personal observation but there may be some immediate effects of taking it in and the window 12 to 24 hours that means you can't really activate to the level you should. So

Yeah, I don't know if you have followed this at all, but um I believe that I think that Brian Johnson said rapasin aged him and so he stopped taking it. Did you see that at all?

I saw that. Yes.

Do we I don't know what his reasoning for that was, but um using biomarkers I believe. Uh but I think that um it's a little bit misleading. So, uh, and let me let me let me take a step back with Brian, you know, because I think that he's, um, first of all, he's he's I support what he's doing and conceptually. I have problems in the details.

So conceptually, he's trying to, you know, modify his himself, uh, modify his lifestyle, what he takes, what he eats, how he behaves so that he'll live a very long time. And he's testing that on himself. And, and I think that that's really interesting. I support hackers trying to do that. I think it's a, you know, it's it's their body first of all, and I'd like and I really think it's important that people take charge of their health and become their own best ambassador for their health.

Um, I think my concern with him is he's doing too many things at once. And if you're taking 20 or 30 different kinds of pills a day, um, then it's really hard to know what's happening. And for instance, you can go through his list of supplements and at least I I don't know what he's taking right now, but when I did this last year, at least seven or eight of them inhibit the mTor pathway on their own.

And so and then if you're adding rapomy on top of that, you may be turning it down too much. You're not you're not restoring the dynamic range. You're turning down activation at that point and that may be that's probably bad for aging. So,

You know, I encourage people to do one or two things. monitor what's happening to them and then if they don't like the the changes in their biomarkers and we can talk about what those biomarkers are. But if they don't like the changes in their biomarkers, maybe do some course correction, go off of one, try another one. If things are working, go off of one of them for a while, see if the effect goes away. I think that you really have to do that kind of experimentation to optimize your own health and and just taking a a whole stack of different things is just rolling the dice. If if I do studies in mice and I start combining two or three things together, I can't predict what's going to happen. Sometimes they cancel each other out. And so, um, the these these these supplements and drugs interact with each other, not just with your body. And so, if you're taking, you know, a pill that's supposed to have 10 things in it, unless they've tested those 10 things directly together, then I can't predict what's going to happen. So, that's what I'm concerned about with him. I I think that overall what he's trying to do is great, but the the some of the messages I think are misleading. So

Yeah, that that's super important. And that's also, you know, more of the direction that I'm trying to go is trying to do less. I mean, I also, you know, um have been doing this for so long, like over 10 years, and then I had, you know, I opened this like longevity medicine clinic in like 2019ish. And so you it's like a candy store, right? Like you have literally access to everything. doing every IV on the planet and all the things at the same time. And I'm like, I can't I have no idea. You know, you and I chatted briefly about the ovarian age test that I did and the result that I got initially is great. That's exciting. But I couldn't tell you what was it. I mean, obviously the lifestyle things I'm sure have been a big contributor if you know we believe this score is really accurate. But I have done so many other things too. I mean I was doing curcumin IVs at one point and all this other stuff. So it's like what helped what?

Yeah, I'm kind of like that too. my own experimental organism at this place. So

Yeah, I mean I love that what I do is like what you're doing now. I'm trying to do one or two things at a time and then and see how that's affecting my body. So

Yeah, I mean we were chatting about it, but I'm at this point we know what the science sleep, exercise, social connections, don't smoke, don't do drugs, but on top of outside of that it's so it's a little bit the wild west. We really don't know.

Yeah. So, if people are doing it in a controlled way, I think it's it's not a bad thing.

Yeah. I I tell people that the worst thing is to be doing nothing about aging, right? If you want to be conservative and say, "I'm just going to focus on lifestyle, maybe a couple supplements, and I'm going to wait on some of these other experimental procedures until there's more data." I think that's a defensible argument. Yeah.

If you want to say, "I want to be on the cutting edge. I'm balancing my riskreward uh differently maybe and I I see the the potential rewards of these things as higher than the risk and I want to be out in front trying it. I think that's great too. I think you have to find your your place on this spectrum, right? And from conservative to I I don't want to say risky, but to more on the edge. And uh the thing that worries me is when people are doing nothing, you know, and they're not paying attention to their health. And yeah, I think things are starting to change. Even in the US, things are starting to change. Every two months I go through the airports and so that's my monitor for how health is going. And I think it's beginning to change. But there's still so many people that just ignore, you know, their health until it's too late and they have some chronic condition that that is very hard to do something about. And and that's what I worry about.

Yeah. Well, I I mean, the stats would suggest that that's the majority of people. They're not doing too much. I mean, we do have GLP1s now, which I don't I was trying to recall um what the statistics are for how many people have taken them, but it's it's a very large percentage now that have taken some sort of GLP1 and I suppose now maybe we can even chat about if you are interested in those like GLP1s now retruditide or reda is like you know everybody on the internet is talking about this.

Um I I don't know. I tried a micro dose for a very short period of time and my weight is already pretty much where I wanted to be and it actually suppressed my appetite. I was doing five five units a week. Yeah.

Um and it was increasing my resting heart rate a bit so I just got off of it. But do you think that the the longevity benefits um are separate from the weight loss because it seems as if that's what it's indicating.

Yeah, I it could be. I think we don't know for sure yet and there's just not enough studies done in people that are already at their optimal weight and have good metabolic health and uh we that's where we're the data we're lacking right now and I think the longevity field though has to really pay attention to these drugs and also I'm currently taking lowd dose SGLT2 inhibitor uh uh also used as a as a metabolic health drug and um I don't have any metabolic problems and I'm may you could argue I'm a couple kilograms overweight, but I'm pretty close to healthy and pretty fit. And but I'm taking it just to see what it does to my aging biomarkers because, you know, this is a drug that inhibits glucose reabsorption in the kidney. So, you just pee out a little bit more glucose.

Um and a little salt, too, which is good. And uh for me, that that's probably a healthy thing that there is a slight in increased risk of UTI because you have glucose in your urine. But

Mhm.

Other than that, the side effect profiles are very low. Doesn't affect appetite. Um, and so that's the path I've chosen to go on. But I think these the this class of drugs generally is very promising. They're better than metformin in my opinion. And uh they're worth looking at in the context of longevity. I think the the muscle loss is the challenge. Uh and so if you're taking one, you need to be doing something to maintain resistance training. Certainly for people that are overweight or have metabolic problems, they should probably be doing something because get that's definitely accelerating their aging. For healthy people, I think it's still an open question, but it's certainly a promising uh both of those classes of drugs are promising, I think.

And what biomarkers, and we haven't talked about biological aging yet, which maybe that fits in here, but um what biomarkers are you looking at to see if this is efficacious?

I look at a wide range of things. I I think that we have uh developed this clock called lineage too uh at the National University of Singapore and this is Yan Gruber and Funong and a little bit of help from me uh so it's a big collaboration there at the university and the reason this was developed is we wanted something that was actionable. And so a lot of people are using DNA methylation clocks uh and other kinds of clocks uh to measure your biologic age and we can take a deep dive into that if you Um basically I don't believe that there's anything special about DNA methylation. You can measure biologic age from protein composition from RNA composition. You can measure it from metabolite composition. You can measure it from microbiome composition in your gut or even your facial structural changes with age. So you know any complex data set if you have enough people you can develop a something that predicts their chronologic age.

The challenge with that though is that these things are not actionable. If I say there's 10 methylation sites that are making you 10 years too old, the doctor says, "What am I going to do about that? Why not?" And so I thought they were not these these clocks are not getting enough traction in in a medical situation in hospitals with doctors um and even longevity clinics sometimes are scared of using them because they want to see their their clients doing better over time and if they don't know how to make that happen they're afraid to use measurements like this. So uh we decided can we take standard clinical chemistries things you measure all the time things you should be getting when you get a health checkup you know LDL HBA1C you know these are the standard stuff and can we develop a second generation biologic aging clock that predicts mortality so it gives you your uh risk adjusted age so if I say you're 40 it means you have the mortality risk of a 40 year old um and can we do that from these parameters Because if we can, they're all actionable. If you're if if LDL is what's driving your mortality risk, we can bring that down, you know. And so if blood pressure is what's driving your mortality risk, we can bring that down.

And so, uh, Yan and Fun have done a lot of work now to to optimize these clocks and I think they're working. We can take people, baseline them with these measurements, and then we use a linear strategy to so we get principal components out of it. Mhm. We can figure out which components are increasing their biologic age and then target those components and then over 3 to 6 months even with just on label medication over 3 to 6 months we can often bring down their mortality risk or with lifestyle. Now the next step is to see what do these ger protectors do? Are they even more effective than statins or something you know and and are they generally effective? Do they bring down biologic age in a wide range of the population? But for now, this works because a hospital looks at this and say we're measuring aging, but we know how to modify it. And we can do it using on label medications, which a lot of doctors can can get behind right now. And you know, with ger protectors and longevity clinics, there's still a lot of skepticism out there. I'm very supportive of them, but in the standard medical community, they're not yet getting widespread acceptance. So

Yeah, I um I mean I started doing biological age testing like the epigenetic testing um many years ago, but I actually pulled it like from what I'm doing on a consistent basis, you know, because a mutual friend of ours, you know, Matt and his whole situation of like sending out the multiple tests and at the same time and getting wildly different results and and also I feel like a responsibility is having, you know, an audience of some level to tell tell them to do something that is actionable like what are they going to do with and the test. Let's say it's like I don't I forgot like between what five and 100 $500 or something. If you're going to spend $500, you might as well do something that's going to be more actionable as you're saying. So,

Well, this is kind of a two-way benefit. You're you should be measuring all these markers anyway. In fact, a lot of them are reimbursed in your standard checkup. Um, but on top of that, we're measuring aging for you. I we do the methylation test in the laboratory. I think they're from a research perspective, they're interesting. Also, from, you know, we collect 100 500 samples and run them all at the same time under the same conditions. They've all been in the freezer in the same freezer beforehand. They're not being shipped across the country. And so we if you do that, you can really get reproducible results with something like methylation testing. The problem is if you're looking at it from a consumer perspective, nobody yet has convinced me they can get that level of reproducibility if you're taking blood or saliva and sending it across the country. And um I I I like what these companies are trying to do and but I I'm not sure I've seen compelling data yet on that. Um and again, there's an actionability issue with them.

So is it just I mean because like Matt setting off the exact same test, same sample, same day, same time, etc. Is it just degradation of the sample on the way to the lab?

Is it's unclear what happened there and and and I use that data in my talks too. But I think it the caveat to that is that's n equals one. You know, anything could have happened in that one sample. It would be interesting to have you know 50 people do that um and see how how how uh consistent the data really is. Now the other thing about methylation is it varies you know morning evening you know you can get slightly different readings at different times and so there is error in these measurements and that's you know up to four years average. So if you measure three months apart you know you that noise is something you have to take into account. So you really need to look at trends over time with these tests. And um you know I also really like the second generation test. The the first generation test predict your chronologic age and then the deviation from that your chronologic age is considered your biologic age. But what we really know is that that deviation is noise in the measurement noise in the experimental approach and probably biologic age. So, it's it's not strictly biologic age you're looking at there.

So I think the first generation clocks are interesting, but they're not the best ones to use. If you're really interested in your own health, I the second generation clocks that measure an outcome like mortality. Those are more interesting because they're predicting the future, uh, which is really what you want. You want to know how healthy you're going to be in five or 10 or 20 years from now, not, you know, what your current deviation is. That's less important, I think. So,

Yeah. Do you think that the um I've heard that maybe the pace of aging, would you identify that as a second generation clock? Is that one more accurate? And let's say if you have, you know, a 0.5 pace of aging, do you really feel as if you're only aging at like half the speed?

Yeah, I I think those clocks are less developed. The one So, you know, the clocks we've been talking about sort of measure the odometer in your car, how many miles are on the car. uh whereas this clock is trying to measure the speedometer in your car with and uh I think that those I think it's fascinating. I use that test uh the Denedian test and uh um I'd like to see more tests continue to be developed along those lines. The the challenge is getting I think we can make much better uh clocks if we have better data. And what's really still lacking is really good longitudinal data. So looking at the same people over time to see how they're changing.

Um but yeah, I think the pace of aging clocks are interesting. I think the Oregon aging clocks are also interesting. uh and it come there's like a fundamental question in the field right now that not everybody agrees on and some people will tell you you're just a set of different organs aging at different rates and we need to identify the organs that are aging the fastest and that's where we need to do interventions and other people and I guess I'm in this category would say that no there is a systemic aging process in the body and we need to measure that um and then when that process starts to break down then knowing the organ age is really important because it's telling you which diseases you're going to get at that point. Uh so to me it's a combination of looking at the systemic level and then at the specific level.

Um but uh you know, the so the organ aging clocks are also interesting. They're also less developed. They're getting better but I think you know if you're really interested you need to be looking at different levels.

Is the lin age available for anyone to use at this point or just something that you guys are working with in your lab?

It's being developed in in uh for widespread use in in Singapore through the NASA University system and we're commercializing it right now. And so we're typically looking at doing it through a B2B uh approach because we there's a lot of information in there and we want to work with doctors and longevity clinics and hospitals to disseminate that information. We haven't started going direct to consumer yet. I think that's interesting. But you know there also we need to comply with the uh regulatory issues around disseminating medical knowledge. So right now this is not a medical test you know uh and it and we give the information to doctors.

Do you guys anticipate using like u you know machine learning um to you know further because the test that I did for the ovarian aging you know it's like an ML model.

Yeah, that's what this is. It's a it's an AIdriven model. Uh so we had we took the inhanes data set which is um a large uh retrospective data set. So there's follow-up data for 20 years on mortality. We need that. We're trying to predict mortality. We're not predicting age. So you need a data set over time. So you have followup on people and uh so that then applied AI approaches to that and and you know you can we're looking at nonlinear AI approaches too but which may be more accurate but you give up explainability a little bit with that. So if you can't explain why it's happening then you can't intervene and it's not actionable again. So the type of AI you use influences whether the accuracy but also the the the actionability as well. So uh we're looking at those different approaches. Yan and Funan are looking at UK bio bank now too to try to get more data to improve it and different strategies. So

Yeah, I I love that. What do you agree with the idea that you know the aging is like nonlinear? So, you know, and it probably looks different for women and men, obviously, since women have menopause, and I'm so excited to get into all things like ovarian aging, but um what are the main spurts that it seems like we're aging at?

Yeah. So, so let me take those two questions separately. Um I think that the data is beginning to show that there's there are transitions, that it's not a linear process. And one of the reasons I tend to believe that is two very different kinds of approaches. is, you know, Michael Snyder did one study on this and and Peter Fedichev and Gerald did another study and they both showed that there's transitions around that 40 to 50. There's a big transition, then another one around 65. And so when you have two different kinds of data analysis that sort of converge on the same uh results, then I think it's something that's certainly worth following up and it may be real. Um so yeah, I think it's probably true that uh there are it's not just a linear progression um regard definitely men and women age differently and uh you can see this just in the animal models you know if you look at interventions that extend lifespan I'd say the majority of them differentially work in males and females some work better in females some work better in males there are a few that work in both uh but clearly there's something going on uh related to to sex and the

Probably it's sex hormones. Uh, and then if you layer menopause on top of that, because the animal models we study don't get there. Only a very few species that actually have menopause. For most animals, there's just a steady decline in estrogen over time. Um, and so when you layer menopause on top of that, I think it's even more important, uh, the differences between males and females. And we, I still think we, even even now, we underappreciate the acceleration of aging that happens, uh, with menopause in women and probably also with andropause in men. There's a big debate about testosterone supplementation that we can get into as well. Um, but I think that probably contributes to aging more in men than we, than we realize.

>> The decrease in testosterone.

>> Yeah, probably.

>> Because it's, it may not be affecting

>> Lifespan as much as it is health span.

>> Yeah.

>> You know, and and I think that may be true for both. You know, they women live longer, but they have a longer period of decline, too. And that's probably largely menopause related. And I, I think that

>> Probably if you look at testosterone levels, you would find something similar in men. People that the men that have low testosterone are probably having longer period of of uh, I guess six, six.

>> Yeah. Yeah. It's like suboptimal function as well.

>> Um

>> Yeah.

>> So, are are you a fan of like, um, bioidentical hormone replacement therapy for both or either sex?

>> I think again, for men, it's about measuring, you know, it's like we don't want to go to too high levels.

>> Yeah. Yeah. And and

>> Men definitely want to be there.

>> Yeah. That some of men want to be there, but there is risk associated with this. There's prostate cancer risk and other things. So, um, let me take a step back because I think this part of this comes into, uh, allowing the person to decide what they want to do.

>> Yeah.

>> You know, because you, you might make different decisions with testosterone supplementation. You might say, you know, I'm really worried, I want to minimize my risk of dying from some disease, and so in that case, I'm not going to supplement. You, you might say that I value, you know, my ability to function. I like playing tennis. I want to do that when I'm in my 80s. You know, I like having, being vigorous. And, uh, and I think that, um, I'm willing to take a little bit of extra risk for better health during that period of time. And that both of those are valid opinions and, and I think we need to allow people to, ideally, we educate people and let them make those choices.

>> Um, but if you're going to supplement with testosterone, I think it's really, uh, um, important to know where you are first and not go too high.

>> Uh, and certainly probably bioidentical is a good way to go.

>> Um, um, you know, I think I can talk about Matt. You know, he's been public about this, but he, uh, his testosterone was low and he, he took, I don't know what strategy he took, but he increased his testosterone and he gained like 15 pounds of muscle. And I saw him, I'm like, I need to do this, too. So, then I tested mine, but it's actually not low, so it's pretty normal. So, I'm like,

>> It's a chance to gain muscle mass.

>> Yeah.

>> Yeah.

>> Yeah. I mean, yeah, that's pretty pretty amazing. I mean, I haven't followed really the data on on men too much, but

>> With women, it seems also to be like

>> A a good longevity strategy for replacing those hormones, you know, from cancer and bone density and all all these different areas potentially. Well, not maybe not so much cancer, but like cardiovascular intervention.

>> I'm surprised that for, I mean, for bone health, for all all kinds of health in women. Um, I'm surprised at HRT hasn't taken off more than it has. I mean, I know there were some studies that were, uh, misinterpreted, unintentionally misinterpreted, you know, that suggested there was high risk of of hormone replacement therapy. And I know that triggered doctors not to prescribe it. I understand the history of this, but I mean, come on. For the the question shouldn't be, you know, should I do HRT? For a woman, it should be, is there any reason I shouldn't do HRT?

>> And there are reasons. You, the cancer risk and other things. There, there are people that probably shouldn't be doing it, but for the majority of women, I think it's

>> Especially if they started, you know, during that perimenopausal period or right after menopause,

>> I think it's beneficial. And, uh, you know, I go to countries, I always ask the doctors, you know, how much hormone replacement therapy. And you go to countries and it's still under 20% in a lot of countries. And I feel like we're, we're really, you know, hurting women's health by not not taking this seriously and pushing those numbers up.

>> Yeah. I mean, I heard the statistic is like ultra low. It's like 5% of women are on hormone replacement. But, you know, that really, the Women's Health Initiative really did do so much damage because even, you know, my mom, my mom is 53 and she went into menopause at, um, 47, so early.

>> And but we live very different lifestyles. But, you know, I told her, I said, Mom, you know, you got to get on like hormone replacement therapy. And she went to her doctor and she doesn't have any risk factors that would preclude her from being on it. And he said, oh, no, it causes cancer, you can't be on it. And I'm like, what?

>> And

>> We're still pushing that narrative like in 2026.

>> I agree. And I, I think on a broader perspective, this is a a real problem. And we have this like idea of the Hypocratic Oath, right? And nobody's read it, but everybody, everybody says they follow it.

>> Yeah.

>> I actually read it, you know, because it's, they have it plastered all over the walls of the medical school in in the US. And so I stopped and read it one day and, um, it has some interesting things in it. First of all, it says that, um, if you have a knowledge of medicine, you should convey that knowledge of medicine to the next generation at no cost. Basically,

>> I don't think Harvard Medical School read that part.

>> I don't want to single out Harvard or all of them do that, but

>> I think it nowhere does it say really first do no harm. I mean, it's kind of a little bit implied, but that's the thing that comes out of everybody's mind. And then they, the next step people take is that well, if people aren't sick, we're not going to do anything for them because we could harm them. And I think doing nothing for people is harming them. You know, we should be trying to really focus on people's health throughout their life course, not only after they get some ICD code, you know, and the fact that we ignore people

>> Uh until they get sick is a really bad way to do healthcare because once they get really sick, it's really hard to fix them.

>> Whereas, I think there are a lot of small adjustments you can make during the life course that will keep them from getting sick until later. And so, you know, if, if you're not getting any medical, uh, advice or any health done, help not being supported in your health now, uh, you need to go find some way to do that because

>> Not only is it about preventing disease, it's about optimizing performance.

>> Yeah. You know, if you're taking a good lifestyle approach, maybe some of these supplements, maybe some of the devices, it's going to improve how you think, how, how much, how you exercise. Like I have a couple supplements that for me improve how I exercise. I, I take it not because those supplements, not because 20 years from now I'm going to be healthy. Well, a little bit because of that, but a lot, a lot because of the fact that I feel better and function better now. And one of the things is that we don't tend to talk about is I think improving performance and enhancing longevity are highly overlapping strategies. Maybe 80% of the things you do for longevity also will enhance your performance now. And so we should focus on both of those together, not just, you know,

>> What do this stuff in 30 years from now, you're not going to be sick. That doesn't motivate most people.

>> Yeah. Um, but do this and in three months, you're going to be, you're thinking more clearly, sleeping better, maybe your stress is down, your exercise is more effective. That motivates people if they feel that, you know, and so I, I want to focus more on that.

>> Yeah. I mean, I think that's what we have most in our control at this point anyways. What, what can we do right now? What, what are some of the things, what are some of the supplement or exogenous molecules that you're interested in right now?

>> Well, right now I'm doing three things. I mentioned the SGLT2 inhibitors. I'm taking that off label.

>> The, um, the other two are supplements and I, I have to, full disclosure, one of them I helped develop. So,

>> It's a product called Rejuvenant, uh, by PDL Health, and it contains a sustained release alpha-ketoglutarate.

>> Um,

>> And, uh, for me, that's lowered biologic age and, uh, I've been taking that for a long time. It also contains, it, there are different products for men and women. Uh, so they both contain, uh, B complex vitamins because we noticed that

>> AKG doesn't work well, what if your B complex levels are low? And then, uh, for men, it contains low dose vitamin A and for women, low dose vitamin D because we saw synergies in preclinical studies with those compounds. So they're all natural products in it.

>> Um,

>> So I take that and then

>> May I ask what's the, um, mechanism for AKG?

>> Yeah, that's no, you can't ask that. This is a, you know, a real challenge because this is a central metabolite in the body. Your body makes a lot of it and uses it.

>> Um, you can't get it in food or diet because it's consumed as fast as it's made in animals. So,

>> Uh, but the problem is you make less of it with aging and, and it participates in hundreds of different reactions in the cell. Uh, and so when it goes down with age, you could, at a simplistic level, you could say that the cell loses its sort of metabolic flexibility. Okay.

>> It's not so easy to convert amino acids to energy or glucose to amino acids. And, uh, uh, supplementing that back up, we think that helps. Now, we can find specific improvements in say, microbiome, it improves red blood cell performance. And getting to specific mechanism is a real challenge. And, and actually the other supplement I was going to talk about is also true. NAD.

>> Yeah.

>> People assume NAD does certain things and it may do those things, but it does many things and what it really does for aging is still an open question. But again, this is a central metabolite that goes down with age.

>> And it, it stimulates hundreds of different enzy, enzymatic reactions in the cell.

>> Yeah.

>> So, uh, and that's the other product I take. I, I've struggled with inamin and NR. I kind of, Matt and I are kind of in the same boat there. I think it's, uh, the taking it orally, unless you take a lot of it, doesn't increase NAD levels that much.

>> Um,

>> And so, uh, there's a company called Ex Bioarma that produces a sublingual version of NAD that goes directly into the bloodstream.

>> And that, when I take that with the AKG, it changes my endurance performance.

>> Oh, nice. I love that. With ND. I mean, I was reading a review, um, of, you know, the ability. So, I, at one point in my life, I was doing the NAD IVs. I just had access to them. Now, I have a whole different like subset of concerns around microplastic exposure with these IV therapies, which actually curious. I mean, that seems to be like a real problem.

>> Yeah.

>> Yeah.

>> These elective IV therapies and the microplastic

>> Exposure. I think that's a, that's a concern. Uh, I don't know that we know how much of a problem it is. Certainly a concern at this point.

>> Yeah. Yeah. The other thing I'm concerned about is I, if you're not doing IV therapies fairly frequently, I'm not sure how much is helping. Like one large bolus of NAD, you come back a month later. I mean, I don't know how often you were doing it, but if you

>> I'm doing it a lot, but most people are not.

>> If you come back a month or two later and do it again, you have, you know, most of that time in between, you, you're not changing your NAD levels. These things get consumed.

>> Mhm.

>> Um,

>> So I, that's why I went to the sublingual approach because every day I can take a gram of it and it, you know, it's

>> And is it NRMN or N itself?

>> Okay. And that makes it into the cell. Okay.

>> It, yeah, that's an interesting question. It makes it into the bloodstream. They have good evidence on that. And, uh, how NAD, NMN, or NR gets into different cells is still a research question. And, you know, there's a huge debate right now between whether NR is better or NMN is better for doing that and how those molecules, uh, get into cells, how much they change NAD levels in different tissues. Uh, I'm, I haven't generally taken sides on that because we haven't done a lot of research on it. Then, you know, the NAD IV or the NAD sublingually is putting NAD in the bloodstream and,

>> Uh, the, there's a lot of skepticism about how that gets into cells. Um, there are papers suggesting they're receptors that can take NAD up directly, but they're, they're very preliminary data so far.

>> And maybe it has to get converted back to something else to get in. These are still open questions. What I know is when I take this, you know, what happens to me is that, um, and I have to take the AKG too. If I go off either one of them, it slowly goes away. So, if, if I take this, my heart rate goes up normally when I'm run, I'm a runner. Heart rate goes up normally.

>> Um, my respiration rate doesn't go up at the same pace.

>> So I'm breathing more slowly and exercising at a better, higher level. So for me, it's improving exercise performance.

>> Great.

>> Maybe that's a vascular benefit that I'm getting better oxygen delivery to tissues. I don't really know what's happening. And I also, you know, again, this is very personalized.

>> Yeah.

>> Whether those two things would have the same effect in you or someone else's, we don't know. But I think that's one of the points I want to make is that

>> You have to find the things that are working for you. You know, don't just take things and don't test and don't measure. Don't observe how your, your body is changing.

>> Yeah. I've taken a lot of other things I didn't notice an effect of, so I quit taking them. So, so I think that, um, I found things that seem to work well for me and that's really the challenge for people.

>> What about some of these? So, I'm so fascinated because now I've kind of like I flipped my entire longevity strategy to be about ovarian aging at this point, you know, because I feel as if I can push that out. Obviously, we know that we can push out a whole bunch of other things

>> That come along with it.

>> Yeah.

>> Um, so mitochondrial function is is huge on my list because as we know, in the oocytes, there's the highest density of mitochondria in the entire body. It's really wild.

>> Um, do you think that there's any,

>> You know, I have some mitochondrial function tests here.

>> I actually haven't done my first one. I will be doing it soon, but do you think that those are are valid? Have you seen those at all? Um, and then what about some of the mitochondrial, I suppose supplements? Maybe like urolithin or something of that nature?

>> I, I know about the testing, but I haven't looked into them deeply enough to to really say. I think it's an interesting avenue if, certainly if they're accurate, I think they're probably interesting tests for people to be doing.

>> Um,

>> Mitochondrial function is important for ovarian aging, but it's probably very important for general aging as well. So, you know, what I'll come to urolithin in a second. One of the things that I wanted to mention though is that we have a paper that's being reviewed right now and it, we took a lot of geroprotectors. So these are drugs and supplements that have been reported to extend lifespan somewhere in animal models, usually worms, flies, or mice, or or there may be human data, and then we tested those for ovarian aging. So, first we started in worms and hermaphrodites and showed that it, in whether it increases their period of fertility or not.

>> And then we have retested that in stem cell models and and mouse.

>> Um, and the, the, the take-home message is a large percentage of these geroprotectors also delay ovarian aging. So, you could interpret that to mean, well, the things that are affecting aging in the whole body are relevant in the ovary as well. Or you could interpret that that

>> Some of these interventions are actually working because they're slowing reproductive aging and that's having a knock-on effect on the rest of the body. We don't have the answers to that yet, but it means that most of these molecules that are geroprotectors are good candidates to, um, delay ovarian decline, potentially extend fertility, uh, delay menopause. So, um, there's, and, and if you look at the literature, there's already data on AKG, there's already data on NAD precursors, there's already, and not our data, there, there's already data on, um, um, metformin and rapamycin. And there's a clinical trial going on with rapamycin with eudaimine so at Columbia, good friend of mine.

>> And so that's really interesting. Um, we found a lot more molecules, one of which is urolithin, which is a very robust effect on frailty in our studies, but also on, uh, female fertility. Uh, so, um, I think urolithin is a really interesting molecule. It enhances, uh, autophagy and then turning over damaged mitochondria leads to production of new mitochondria. So it enhances mitochondrial biogenesis as well. I think it has other activities as well, but it's a,

>> I think it's an intriguing molecule. I haven't tried taking it myself yet, but it's certainly on my list. So,

>> Yeah.

>> So, what were, can we walk through all the things that you have kind of tried on the animal models with the ovarian so aging? So, NR or Nmen or NAD, one of those?

>> Yeah. Um, we see small effects with that, but not big effects. Um, uh, we see rapamycin, and we can repeat that in our animal models.

>> Um, and, uh, we've seen that metformin can be repeated, as I mentioned, urolithin, a, um, spermidine is another molecule that seems to have another molecule I think is very interesting and it has effects on, uh, fertility as well. And then a range of drugs that we tested as well. So, not all of this is published yet, but, um, we're still looking at IP, so I can't talk about the drugs in too much detail, but the, um,

>> Are any of, I can't, maybe you can answer this, but are any of the drugs like anti-fibrotic drugs to help with some of the thickening?

>> The molecules we took drugs that have been reported to affect aging generally. Okay.

>> And so, I'm not sure we tested any of those. I have to go back and look. So, there, we tested a large number of things. Are not all in my head at the at the moment, but, yeah.

>> Those would be interesting candidates for sure.

>> Yeah. I mean, because it seems as though one of the mechanisms we have, the mitochondrial decline,

>> The stiffening of the ovarian tissue itself,

>> A shift to more sympathetic state in the ovaries.

>> Um,

>> There's, I mean, we, we were trying to ask a specific question. Do

>> Are geroprotectors more likely to affect ovarian aging than just random molecules? And, and, and we found a very strong, robust connection there. But, uh, we didn't look at the wide range of things just from an ovarian perspective. So we could go back and try to do that. What, one of the things we're doing right now, um, I never thought I would say this is that half my lab is AI now. So,

>> We're doing a lot of, uh, drug screening sort of in silico, looking at, um,

>> Um, large language models and interrogating drugs that might affect longevity. We're doing that with peptides now. I think peptides are a really exciting space too.

>> Um, and, uh, we're also using transcriptomic data and omics type data to try to find new drugs that affect longevity. So we have a couple papers that are under review looking at that now too. I think that that's really exciting. The, the uses of AI are, or in the field are just expanding as we go. I'm not sure I'm going to be necessary much longer, but that's okay.

>> No, I, I don't think so. Um, to go back to the ovarian aging real quick. So, what have you found most efficacious so far?

>> Yeah. Um, well, we're really looking at, um, I, I mean, I think first of all, I would, I would start with you study on rapamycin. Um, you know, that's a, the short-term clinical study in women looking at AMH levels and other, uh, hormone levels. It's not looking at fertility. I mean, there might be, there's some concern about using an mTOR inhibitor in women that are trying to get pregnant because it could affect early development. I,

>> So, um, but I think in terms of the data, it's very promising for ovarian aging.

>> Um,

>> And then, you know, I think some of the supplements look really promising as well, and those are things that people could take. So, and are less risky. So, the AKG, the NAD, you know, the, the precursors, those things are available and may be beneficial. Spermidine's available.

>> So, you know, we try to balance it, right? Because ultimately finding new drugs might have bigger effect than supplements.

>> Uh, but supplements are available now,

>> And can be commercialized now. And so we want to have an impact now,

>> And also look at things that might have a bigger impact later.

>> Um, we've also looked at strategies where we could target things specifically to ovaries. So, and, and we're trying different antibody driven strategies to do that. So, that might be a way to get a bigger effect specifically in ovaries because if you have a molecule you can't dose too high,

>> Then you could, if you target it directly to ovaries, you might get rid of some of the side effects associated with it.

>> Yeah. Well, is it reasonable to say that the ovaries also could be a good model to understand aging better as a whole, considering it is an organ that ages so rapidly in comparison to?

>> Yeah, the ovaries and the thymus are the two things that a seem to age very quickly in the body.

>> And that some of the, the thymic effects may be having a lot of downstream effects on inflammation, you know, later in aging. But, um,

>> You know, it, it's crazy. We've, we've ignored, um, reproductive aging, particularly female reproductive aging.

>> Uh,

>> Um, people probably over the years doing research with not enough X chromosomes. But, uh, the,

>> But we need to go back and rethink about that because it's really an area that's

>> Ripe for, uh, experimental exploitation. And I think we can learn a lot about, um, reproductive aging, about aging in general, uh, from from doing studies and looking at ovarian function.

>> Yeah.

>> And male reproductive aging too. But, but I think that, what's missing right now is the ovarian studies. So,

>> Yeah. Yeah, I agree. I mean, I think, um, you know, big thing that I've always been about is like this mitigation or reduction of like environmental toxins. But there's, you know, some some good research out there that shows higher levels of different PAs, environmental toxins

>> Equals shorter reproductive, you know, timeline. So I think that's, that's a big, that's again, something we can do now. We can have less of that in our environment.

>> Yeah. And I, I really hope that that becomes more mainstream because, you know, as an individual, it's difficult to do that. You know, you, you've accomplished a lot of that, I think, but there's a lot of effort that goes into that.

>> Yeah.

>> How do we scale this so that everybody's exposed to less toxins? And, um,

>> Yeah.

>> Right now, there's just not enough acceptance and, and we have, you know, politics around the world that are driving us in the wrong direction in terms of, you know, cleaning up our environment and, and, and the exposure we have to different things. And I hope we can start to change that.

>> I know. I mean, and also, are you friends with David Sinclair?

>> Yeah, David and I know each other pretty well. Yeah, he was on the pod, um, a while back, I think, and like when we were both in Gstaad for the longevity masters conference or something.

>> But, um,

>> I didn't go last year, so.

>> Yeah, I didn't go last year either, but I, I think it was the year before David and I were both there, maybe.

>> Um, but he was, he told me he thinks like that microplastics are like one of the largest threats to humanity.

>> Yeah. Yeah. And I think a lot of doctors are talking about this now, you know, like Jordan Schlein and, you know, he spends a lot of his time trying to, uh, reduce, uh, microplastic exposure and it's not as easy as as you might think. I, I think that, um, we need to, you know, we've just, and that's an emerging field. We need to pay attention because it's probably accelerating or aging. Although, you know, sometimes people are very resistant. You know, one of the things that strikes me is how much life expectancy was going up in China

>> During this, you know, heavy pollution. I mean, pollution's gotten better in China recently, but life expectancy from like 1990 to to 2010 was going up dramatically. And arguably,

>> People in China live as long as Americans do, and they, they're exposed to a lot more pollution on average.

>> Um, so we need to be more nuanced about it, too. We need to understand what the toxins are,

>> What the effect is, and which things we need to get rid of because we're not going to go back to Eden. We, we need, we need to be strategic about how we reduce exposure and so there's a lot of research that has to be done. But I agree with you. I think

>> Microplastics are a big concern right now.

>> Yeah. Well, I mean, I, you know, I try to test like kind of everything that I can, and I've been doing this total toxic burden test. Have you ever done that one?

>> I, I haven't done that. And I've had some toxins measured and so,

>> It's pretty comprehensive. I mean, I love it. I always want to be on the side of caution, like let's just have no high level of toxins, measures BPA and glyphosate and parabens and phthalates and Pfas and,

>> You know, molds and microtoxins, all sorts of stuff. So I love that test, um, because a lot of times people can be living next to, let's say, you know, some sort of manufacturing plant. They have no clue that they're getting exposed to this really high level of X chemical, you know, and if you know, then you can make different life choices.

>> And also just mold. I mean, that, that's the big effect on people and a lot of people don't realize it. It's, uh,

>> Yeah.

>> Yeah. So, but all of these things, I think are relevant and I think we could stop worrying about windmills and start worrying about these things. It would be great.

>> Yeah, I agree. Um, to go back to the rapamycin, is the mechanism of why it could be extending the ovarian longevity? Is it because there's less eggs being recruited and then less eggs are?

>> Well, there's certainly anti-inflammatory stress going, or inflammatory stress going on in ovaries. So, it's doing that. It's probably stimulating more, uh, egg prod, well, better egg development, let's say in ovaries. Uh, and so you can see better egg quality in preclinical models when you look.

>> Um,

>> >> And, you know, better proteostasis is going to be, you know, beneficial, increased turnover of damaged proteins, oxidized proteins, all of these things. Rapamycin is linked to all of these things. And this is this is why people don't like interviewing me because, uh, you know, all of these longevity interventions, I can point to every hallmark of aging with them. And so it's hard to give a specific answer, but I think that

>> You certainly see elevated mTOR signaling in ovaries, you know, with age.

>> And, you know, elevated baseline signaling, mTOR signaling in ovaries, whether it's in muscle, whether it's in the brain, it's contributing to aging. So turning that back down is going to have broad stream benefits.

>> Yeah. Yeah. One of the interventions that I want to, you know, test after hyperbaric is red light therapy. You know, strategically maybe knocking down the oxidative stress and because we know that we have that inflammatory cascade that occurs in the ovaries at X periods of time,

>> Maybe if you dampen that, that could be beneficial.

>> Yeah, I think that it's how to penetrate the red light to the tissue is the challenge. Uh, so I, I've tried red light therapy just on skin. You know, there's some good data on that. I don't think it's completely convincing yet, but I, I think it's, it's, it's worth looking at more and maybe worth trying. Uh, but delivering it sub, you know, into the body is a bigger challenge. And so that, that, that's the concern there.

>> You know, I think cryotherapy is interesting too. I don't know if you've tried that.

>> Yeah. Try it for the going into the minus 87 room for three minutes. It's

>> Yeah.

>> It's, you, you definitely feel better immediately after you leave the room.

>> Oh, yeah. You feel it increases dopamine. I don't know that there's

>> It does, I think.

>> Yeah. I mean, we know that we have, um, like data on cold water immersion. I don't know if we have as much on cryotherapy, but I would assume it's like somewhat similar, but, um, yeah, I mean, the increase in dopamine and like norepinephrine, you know, really, really good. But yeah, I mean, that makes a lot of sense to me, you know, because we don't have a lot of information on this. I kind of just have to, you know, I do a lot of like first principles thinking, I suppose, like how, what could potentially

>> Yeah, I think that's good. Yeah, it's good. I mean, it's all we've really got right now. So,

>> Yeah, it's good. And, and I, one of the reasons, you know, we started a consulting company, Live Beyond, and one of the reasons we did it is because we want to work with clinics that are doing these things. Uh, we want to see what they're doing,

>> Uh, and, you know, whether they're effective or not. So, we get to look at data.

>> Uh, and we can't always publish it. Sometimes, sometimes we can, but we can at least see what's happening.

>> Because a lot of these therapies are really expensive right now,

>> But you could scale them, you know, if you, if we had data that they're working, we could really scale it. And

>> What we're doing at in US is really about, you know, democratizing longevity. The interventions we're testing are repurposed drugs or their supplements that are relatively cheap. The biomarkers we're losing using, we're trying to keep that at a cost-effective level so that you, we can deliver something to the whole Singapore population.

>> But at the other end of the spectrum, you have stem cell therapies and gene therapy and and all kinds of other things that right now are not scalable to the population, but I just want to see the efficacy data there. If they work, we'll figure out a way to do it. So,

>> Yeah. What are your thoughts on therapeutic plasma exchange?

>> I, I think it, I think it's really intriguing. Um, the, uh, uh, we, I haven't tried that myself yet. Uh, but, uh, people that have, I think are pretty positive about it and, uh, there is some, I think pretty credible published data that you get longevity benefits from it. So I'm, I, I'm not ready to say I'm 100% behind it, but I think the data is getting there.

>> Yeah.

>> Yeah. I did it. I have a, I had like an interesting end of one experience because I did it smack dab in the LA fire. So I had had the highest toxic burden.

>> Maybe a good time to do it.

>> Yeah. I mean, it was a great time for me personally, but also the information I thought was so, I had about an 11% reduction. So, I did a total toxic burden the day that I got the TPE before it and then I did it a week after. So, I had about an 11% reduction. Obviously, some of the categories higher than others.

>> Um, but then I had another interesting thing. So, after that LA fire, for the first time ever, my TPO antibodies started to increase. You know, they became detectable. They were 12 and then 20. I just think that was kind of like a massive overload.

>> But after I did the TPE, they went back down to undetectable and they stayed there. So that was a pretty cool finding for me personally.

>> Yeah, that's, you know, I, I have Matt and I, a lot, Camberlin and I debate sort of what tier we put different interventions in and I think we both are pretty positive on on TP.

>> So, and do you think the in-use phoresis? Do you know about that as well? So in-use phoresis, it's, um, not available here, but in Europe.

>> Not yet. What, what is this? It's more of like a targeted. So right now with therapeutic plasma exchange, you can either do it by removing all your plasma and then replacing it with albumin or partial. But this is supposed to be more of like a targeted, like let's say you want to,

>> You're filtering out specific things.

>> Yeah. Microplastics, but you also get the plasma back, which I like because I do have some questions about this albumin that's going back into the body, you know.

>> Yeah. Yeah. I, I agree. I, I haven't looked into those specifically, but conceptually, I think it makes sense.

>> Yeah. Question is, you know,

>> Do we know exactly what we should be removing? You know, we know some things that are good to remove, but

>> Will you get the same benefit that you get from removing everything? On the other hand, you're keeping your plasma, which is good. So,

>> Yeah.

>> We just don't know when we're comparing these things right now, which are better. And we, that's why we need to get serious about measuring this data. And I think that everything from supplement companies to device companies, they're, they're less motivated to do the full-scale clinical studies that need to be done. And I understand why. They don't have a billion dollar, you know, pot of gold at the end of the rainbow. If you're developing a drug, you can spend a lot of money on the clinical trials because you make a fortune if it, if it gets approved for whatever indication. But with, with these sectors of the of the market, there's that the, the econ, economic profile is different. So a supplement,

>> You know, you're going to have competition. Other people are going to be selling it. It's going to be hard to capture the market completely and raise the price to wherever you need to to make a profit. So at the beginning, you do less clinical studies and then there's less data on whether it works or not. We need to find some way to deal with that. I feel like, you know, the drugs, um, we've put the bar too high on getting them approved. It's almost impossible to get a drug approved now.

>> Uh, and we're probably missing out on things that work for sub-optimal with different diseases because we're setting that bar too high.

>> Uh, on the supplements, we need a way to get more rigorous testing done.

>> Uh, to figure out what works in which people. I mean, like I said, I found things that work for me, but that combination may not work for you. And we, we need to figure out what works in which people. And we need, there has to be resources that allow us to test that. And right now, either on the private sector or the academic sector, there aren't sufficient resources to test these things.

>> Why does it cost so much money to get, you know, some of this research done?

>> Well, it depends on what kind of research you're talking about. If we're talking about preclinical research, it, um, animals cost a fortune to keep. You know, it's a couple dollars a day for every mouse I have. And if you're doing a longevity study, they're alive for almost three years, or some of them are alive for longer than three years. So,

>> Um, and you have to do a lot of animals to show an effect. So, it might be 200 animals. So, you can add the cost, cost adds up really quickly.

>> Why do they cost so much money to keep alive? My team recently told me that only 50% of you that actually watch this video are subscribers. If you watch this content and you enjoy it, I would really appreciate a quick subscribe. Take a second to do it now because the more subscribers we get, the better the podcast, the better the video content can be. So, would really appreciate that. Now, back to the video.

>> Um, because you have to keep them in a in a pathogen-free, uh, vivarium. So they're highly monitored. They're, they're, it costs a lot of money to keep the, the, the airflow correct in the building. And you, there, there are a lot of different things that you have to do in a, in a re, in a high research grade animal facility. Now, there, there, there are people that do studies at universities and other parts of the world that don't have those facilities.

>> Typically animals don't live very long in those conditions.

>> So, you could think of that as a good thing. Your studies are faster, but the problem is you don't know they're dying of normal age-related,

>> Pathologies. They could be getting some kind of cancer from exposure. They could be getting viral infections that are killing them.

>> So, we tend to work in pristine settings where we have a long wild type lifespan and then if we can extend that, that means that we're probably slowing aging. If we're doing things to shorten the lifespan and then compensating for that, we don't know why they're dying in the first place. So, it may not be aging. So, that, that's one of the reasons. Uh, the human clinical trials just cost a lot of money, recruiting people, you know, all the controls and ethics approvals that go into that and the money adds up fast. And if you're doing a phase three clinical trial on a drug, you know, you've got a large number of subjects, probably multi-center study because you want to see that the findings are reproducible across different sites. And so it's, uh, um, money. I mean, I'm, I'm generally supportive of pharmaceutical companies. Okay. I think the vast majority of people in these companies are really trying to do, uh, the right thing and they're really trying to make people have better lives.

>> Um,

>> Yeah.

>> But the industry has gotten skewed toward taking care of sick people and not keeping healthy people healthy. And we need to do something about that. And, you know, I've even had conversations where I talked to a high-level person at a pharmaceutical company and they actually said to me, "Well, great. You know, if you give me a a drug that slows aging, uh, that's good. I'll make a lot of money off that drug, but I'm going to lose money on all my other drugs to treat these chronic diseases."

>> Um, you know, we need to fix that problem. It's a, that's a, you know, they're problems driven economically. You can say that about hospitals, too. Hospitals make money in the US off doing procedures on people.

>> Yeah.

>> If you keep everybody healthy, the hospitals are going to have less business. You know, it's, and so there has to be some sort of strategy that focuses on people's long-term health.

>> Uh, and I don't mean sick care, I mean health care. Uh, and right now the, the economic incentives are not aligned with getting that done.

>> Yeah. Yeah. Yeah. I mean, for now, it just needs to be like a lot of personal responsibility.

>> Yeah, that, that's right. And, and I, the, like you have to invest in your health and, uh, I know that's easier for some people than others. And I know it's expensive for some pe depending on how far you want to go down that path.

>> But, you know, finding a little bit of time during the day to make sustainable changes, if that's all you can do, that already helps. You know,

>> Eating a little bit healthier.

>> Um, another thing I think is people should be wearing these continuous glucose monitors.

>> Um, not all the time, but maybe once a year.

>> Because they tell you how your body reacts to what you're eating.

>> Yeah.

>> It's an ed, it's it's an educational tool for the person wearing it. And

>> It, it helped me have a better diet after because I learned that what I react to and what I don't react to. Like,

>> Yeah.

>> I mean, I love those. I think

>> Yeah.

>> So, these are little things that don't cost much that teach you how to live better lives. And, and I think that's a good place to start for people that don't have a lot of time and money to to to target the, the, the, the more cutting edge things right now. Of course, if you can do that, that's great, too.

>> Yeah. I mean, realistically, the things that move the needle the most are like free or low cost. They just require like a consistent discipline with them.

>> Yeah. Yeah.

>> And I have found, you know, that people, cuz people always just want to ask me like, what supplements are you taking or NAD protocol, you know, and it's like, well, you shouldn't even be thinking about that right now. I mean, if you maybe if you want to, but you got to master these other like, go to bed at the same time every day and, you know, the basic things. But people don't want to do that.

>> That so don't tell me.

>> People don't want to do that because that's hard and it's not fun.

>> Yeah. And then, you know, I think a lot too about like the industry, I feel like right now is being painted as a very like rich person only situation,

>> Which, you know, obviously, like we're sitting in front of a hyperbaric chamber, it can be, but

>> There's also just so many things that you can do that aren't. And also, you know, people should think about, and not saying this in any judgmental way, but, you know, like what is your budget for alcohol like per month?

>> Comment.

>> Yeah. You don't have an alcohol budget, do you? I drink wine.

>> Yeah.

>> Okay. You drink wine? That's okay. I mean, for me, it's zero. So,

>> Yeah. No, that's a big discussion we could have, but I think zero is healthy. I, I'm not sure whether moderate intake is healthy or not, but we, we can come back to that.

>> Well, I mean,

>> You're making a different point.

>> Yeah. Yeah. It, it's, I, I thought that was answered now. Has that not been answered now? Isn't zero better than

>> It's like a pendulum. It swings too far in one direction and everybody's saying, you know, three glasses a day is good for you.

>> I know. That's crazy. But then it swings too, probably too far the other direction and saying that you should not have one drop. You know, I, I'm happy to delve into that. But I, I think your other point though, is, yeah,

>> Where are you spending money and where could it be better spent is a really good question to ask. And

>> And I think, you know, people, people are busy, they've got stressed out lives, but little things make differences. You don't have to accomplish everything at once.

Yeah. If you can find little changes you can make that are sustainable, ideally they're things you enjoy, some kind of exercise you enjoy, yeah, is better than the perfect exercise you don't enjoy, at least to start, you know, and uh um so those kinds of things, if you can accomplish those things at small levels, they fill you with confidence and they allow you to do bigger things. And so I I everybody should be starting somewhere, you know, and and it it's very personalized, but it has to be, you know, something generally that you don't mind doing, you know. I think most people if they don't like doing something, they won't continue doing it.

Um, and I would also say at that point like maybe changing your mindset a little bit like like I have this mindset, you know, obviously a lot of people think I have a super boring life. They're like, how do you even have any fun whatsoever? But I enjoy like going to bed early, feeling amazing. I enjoy like I have a I get to mentality around working out. Like I get to work out. I get to push my body. That's so cool. How many people on this planet don't have that opportunity?

Yeah. I I I feel the same way about the exercise especially. Running is mindfulness for me. So good. And I I started doing resistance training about 5 years ago and it it it builds confidence in me. You can see the effect of it, you know, and there's certain aspects of it I don't love, but I love the effect I get and it's worth. You feel better too, right? I feel a lot better. So, it's like compounding on on itself, which I I love.

Yeah. And when you can start doing pull-ups again and things like that, it just feels good. It gives you belief that you're going to, you know, can do other things that'll keep you healthy. So, I Yeah, I I agree. Um to me, exercise is like especially running because it I'm not good at meditation, you know, I can't, you know, my mind's in 20 places at once. But when I'm doing a long run, that's when I can really focus my mind and and sort of let a lot of stuff go. And uh so to me, it accomplishes multiple goals at the same time.

Yeah. What do you think about biioarkers such as V2 max? I mean, we've heard a lot of chatter about that being one of the best biomarkers for longevity, grip strength, gate speed, all that stuff.

Yeah. And I I think we can take those one at a time. I think V2 max I I on the one hand it is a great biioarker of long-term health. On the other hand, you need qualified individuals to effectively measure this. Now my Whoop estimates it and my Garmin estimates it. They don't agree much with each other, but they estimate.

How far? I' I've never used a garment. I think by uh Garmin, well, right now I'm 44 and Whoop is closer to 40, so I guess it's not that different, but um these things are are imperfect measures. And so trends probably might be interesting, but I I don't think they're great at measuring. They're they're calculating it based on other parameters. If you're really trying to measure V2, and by the way, I'm I really like Whoop. I don't get paid by them. I just I like the sleep data I get from it. I like the. Yeah, you got I like the um uh cardiovascular data I get from it. It's starting to try to measure health span and I don't think it's very well. It measures a very limited set of parameters so it's not very accurate at biologic age yet but for the other parameters I think it's great. I think aura is great too. I I just don't like rings so I I like this personally. I I mean I love Whoop for like performance stuff but from a like measuring basil body temperature as you know ovulation stuff it's it's great with aura but I love the the component of whoop that it can tell you what to do to improve your biological age I think for the general population that's like super powerful.

Yeah, although I get it I get in arguments with it because it's like it's always saying to me your your physical function is great everything's great but your sleep's terrible and um because I'm traveling all the time for one. And the other thing is I've slept five to six hours a night ever since I was can remember. That's just the amount of sleep that I can normally get.

And some people have that gene, right? The short sleep.

Yeah. I mean, some people are much more extreme than that. I've never tested my genetics on this, but that's just how I'm I I sleep very deeply for five to six hours and then that's it. I don't sleep during the day. I'm not tired. And then on top of that, I'm switching time zones all the time. So it's like constantly telling me my sleep debt, you know, and so eventually I said, "Listen, you know, it's not helping me to tell me my sleep debt all the time." And cuz I'm not going to change it. This is how I've always been. You need to work around that.

Yeah. To to give me, you know, advice that helps me, you know, and and it came back and it conversation with me and it said, "Oh, I understand where you are and everything." And then two minutes later it said, "You need to get more sleep."

Well, I don't think they're there yet. they're not like at that. B. But I'm being critical, but I actually really like using it. And uh and it, you know, integrates um you know, with I can enter my a lot of my behaviors. Uh some are a little too personal, but I can enter a lot of my daily behaviors into the Whoop and it tries to correlate that. What I would really like to see is it the statistics it does on your behaviors like, you know, did you do Hbot today or you know, what what drugs you took and it it asks a lot of those questions. But then it does sort of one-off statistics if you took this drug your sleep was better or something. What it needs to do is integrate all of those things and find patterns among the behaviors and not just one versus one.

Yeah. So I'm hoping it can do that in the near future. But generally I'm very positive about and I think people wearing them they get a lot of information that's useful.

Yeah. One thing that I found super cool about HBOT is um that as soon as I get in it logs me as soon as it's pressurized it logs as restored. So really seems to be ultra parasympathetic for me and I've seen that repeat on a lot of people that have come over and done it. And I find that to be so beneficial because we know stress is a big one and specifically for women reporting higher levels of stress.

What about HRV? Do you do you follow that closely?

Yeah. Um it I think that's an important one to look at. Oh yeah. Varies a lot. You have to look at averages, but I think it's an important measure of health.

Oh yeah. Yeah, I did a whole like so from 2023 to 2024 to 2025, I was benchmarking my stress levels. So stress logged in HRV and I was able to make such a meaningful you know change in HRV with just some relatively simple practices to be honest. So, yeah, that's another parameter I look at pretty closely. So, yeah. Yeah, I think that's a good one.

Um I I think resting heart rate's another one that's good.

Yeah, absolutely. I mean mine's like four high 40s, mid-40s. So yeah, it's pretty good. But a lot of people just significantly higher.

Yeah, I think coming back to the V2 max, I didn't answer your question though, is that it's a measurement challenge. So, if you're measuring on a treadmill and you're ramping the treadmill up or stairs or bike or whatever, um, a lot of people they don't want to go, they don't know what exhaustion is. You know, you need to go to exhaustion.

Yeah. But they quit too early and then you're trying to extrapolate and guess. And so, I think B2 is max is great, but it it's really it's easy to measure in athletes because they know where their exhaustion levels are. Yeah. But it's not so easy to measure in a general population. And so you really need good qualified people to get an accurate measurement there. But I think that it's a very meaningful number. Grip strength is a little bit like that too. I mean it's a if you try grip strength test it's painful, right? And so it's it's really combination of strength and pain tolerance, you know.

Yeah. And so um but these measurements are I I think V2 max if it's done right is a better measurement than grip strength. But all of these strength measurements are have value.

Yeah. And grip strength is so easy to do at home. It is. It's like the the thing costs like $30 and you can just do it at home, which I I enjoy. Like I have a set of things that I do at home like long health, like a spometer, grip strength, which I mean my grip strength is like 106. So for like a woman it's incredibly high. Yeah. Um and I don't train grip strength obviously. Um but yeah, these are like nice things. I have this new cool blood pressure monitor too. It's called Connect. So it also looks at some other measurements. It's supposed to be looking at some like arterial flexibility. I'll show it to you if you have.

Yeah, you have to tell me about that one. I I want to get a good blood pressure monitor.

Yeah, it's really nice. Um and but you know, it's interesting because the ranges are based off of like a general population. So like I'm falling below the range like every single time, which is good, but you know, according to my cardiovascular friends and you know, doctors, but um yeah, we need to have better longevity metrics on all of these type of things.

Yeah, I agree. I mean you they fit things to averages. Maybe that's all they can do, but we don't want to be average because the average is like not good at all.

Yeah, I agree.

Um what are some of your favorite biomarkers to look at? Like if someone's listening to this from a longevity standpoint, if you had, I don't know, five to 10, what would they be?

Well, we mentioned a bunch of them already. If you can really go get that uh V2 max, I think that's important. um HIV, uh heart rate, uh all these things are highly relevant at least to many aspects of aging. They may not be telling you everything. Um I'm looking a lot I I would say the biologic aging class you should pick one or two of them to measure if you're going to really go all out. So line age we love course, but there are others available. Yeah. Um then uh you know I'm I'm looking into the the some of the cancer screening tests right now. I just did loosens uh which is uh they screen for circulating circular DNA markers of different cancers of cells. The different cells in the bloodstream. Uh, I've been doing the Grail liquid biopsy, but I think they just got some I feel like they just got a bad.

Yeah, I I don't I'm still not sure how accurate those things are, but I think that we're talking about people that want to go all out. That's a good thing to do.

Uh I'm I think DEXA is good. You know, biopedence is okay, but it's variable, but DEXA is great to tell you about your health.

Yeah. Especially I mean especi for women, you know, so important to do early. think most women are getting a DEXA scan at the age of 65 which is when it becomes. Yeah, it's pretty late. Is super late I mean, what bone density peaks I think at 30. So, yeah, even a little earlier. And and um there are other types of bone density measures that are good. I mean, certainly you should be doing your standard screening. I mean, colonoscopies and you know, those things are are are I'm I'm not talking about those because we're talking about longevity but yeah, you know, don't don't skip the basics to go to the advanced. I don't know about full body MRIs. I'm I'm more skeptical of those because the people I know that take them, they always get some finding. And then it increases their anxiety and then most of the time it's a it's not a meaningful finding for downstream pathology. So it it's uh I I don't necessarily recommend that.

Um yeah. So what else?

I'm you know I'm on the fence because I I'm in such a unique position. So, like I've had I've gotten full body MRIs now every year for the past six or seven years. First one I ever got did, you know, they found a couple of white matter changes and they've never progressed or anything. Something must have occurred when I was younger. But anyways, at that time they didn't really have much data on it. So, they sent me down this like crazy rattle.

You're doing all this testing and.

Yeah, exactly. And and I I don't get rattled too easily. So, I think but some people really could.

Definitely. And then there was another time like you know the last one that I got they they thought that they found a finding I but I was able to just pick up the phone and get in another image the same day. So I was really quickly but yeah for a a standard person not able to do that then they would be like stressed about it.

Yeah, I'm not sure I I think it's a it's a mixed bag definitely.

Yeah. Yeah, I mean I I think the future of it could be really interesting for early detection but I think and then you know there's genetic screening and other things that are pretty standard now that are if you really want to know I mean these are things to be you know you're you need to know your APOE status you know I mean it's like you know your risk for Alzheimer's is you know if if you have this is another thing that people say is non-actionable they say oh if I what if I have two APOE4 alals it's 12fold increased risk of Alzheimer's what am I going to do about it? Well, one thing you can do is take lifestyle much more seriously. Exactly. So, there are things you can do about, you know, we know that exercise impacts onset of dementia, you know, and so there are things that it is actionable and and you should know, you know, I I think that, you know, these kinds of things are I I want to know as much information as I can. Uh same and but, uh I think that's generally a healthy approach. If you were to choose like one, you know, I guess blood chemistry marker from each kind of section, like would you say like um LP little A and then maybe APO B from a cardiovascular standpoint from like a metabolic health standpoint? Would you want to look at like insulin or a home IR? Like what would that kind of look like?

I think those are all good. You know, it's like I I think, you know, HBA1C is a simple marker. It doesn't change that much. It's easy for people to do. I think it's a pretty good parameter for to start at a entry level for for metabolic health. Certainly going to you know more you know you know insulin uh gl glucose tolerance insulin resistance all these things are are better uh but just HBOC is a good start and I use that a lot you know I'm I was at 5.2 and then I'm taking SGLT2 inhibitor now I'm trying to see if I can get it how much down it's going to come.

Nice. You'll have to tell me what the results are on that.

Yeah, it's it's it's only down to 5.1, but it only took you like two months, so it's not not really enough time for it to change yet. Um, and I don't know if that's meaningful yet. U, but um, so that's simple. You know, I I I think the question is what are the good entry point measurements, you know, and I think Apo and LPA are both like the data on those are are really compelling and uh, not enough people measure those markers. people still measure cholesterol and and uh and HDL and LDL maybe and think that's enough and and you know I have high cholesterol but my LPA is very low really low and APOB is not that bad so I'm like not ready to go on a medication for that you know so it's it's um my HDL is super high you know so I triglycerides are really low because I run a lot so I it's you know for me it's like I want to go get some imaging to see what my my arteries look like but.

Like a clearly or something.

Yeah, that I'm going to I want to do clearly. That's the what I've been told. I haven't tried it yet, but that's something that.

I've done that one.

I think if I look fine there, I'm going to just not take medication for it.

I mean, it's such a gosh, the cardiovascular conversation is just all over the place. Um but I mean, it seems like it's a bit seems that there's an indication that it's a metabolic issue, not just a cholesterol issue on its own. But um yeah, I mean, where do you fall on that? So I mean, there's obviously different schools of thoughts on where I I genetically have an elevated um LP little A. So there's that. So I have to have that risk profile look a little different.

Yeah. But um where where do you think like apopy needs to be you know, where would you feel comfortable like at like 30 or 60 or.

I I you're I I'm hesitant to answer that because I don't have enough knowledge of the actual numbers. Certainly the lower the better but I don't know uh I haven't looked at it carefully enough. So I'm just transparent, you know, you know, it's like I I work in so many different areas of the field that I I don't have the detailed knowledge sometimes. So I'd rather just be honest about it to give you an answer.

I think that the the lab cut off is like 80 or so and then but you know there's but I don't know whether 30 is better than 60 or not. I assume it is but I don't know the date on it. So.

It's a good. Yeah. But then it's all like going I mean we believe that AOB is causal for cardiovascular disease but then where is this metabolic role come into.

Yeah, I don't think we have enough understanding of that. I you know I I would look I think the link between metabolism metabolic function and aging is super strong. M you know if I think if you're just going to fix one thing you know make sure your metabolic health is is ideal because you know and that can be done with lifestyle or drugs or supplement. There's a lot of ways to do it but you know if your metabolic health isn't ideal you're taking a big risk for aging. So.

Yeah, and I think the stats on that are pretty grim. I think it's like 6% of Americans at least have like between the five criteria have optimal metabolic health.

Yeah, I mean this this is what's so frustrating about the American health care system. I mean, there's lowhanging fruit here, you know, but there's so many perverse incentives like people selling unhealthy food and and health care system designed to treat sick people and, you know, and politicians that may or may not care about the population. It's just so frustrating that that we can't do better than what we're doing. I can't believe that life expectancy in the US is some the last statistic I saw, we were 60th in the world. I mean, seriously, you know.

60th.

Yeah. And it's going down. Is it going does that real that it's going down now?

Well, you know, it it it was starting to trend down and co kind of complicated that, but it it was starting to trend down. But it's going to trend back up with these GLP1 and SGLT2 drugs and it it they're you know treat they're affecting I I read there were 18% of American households somebody's taking it.

Yeah. It's crazy.

Yeah. And for people that are that need it, it's going to help them. I think so. Um this is uh um going to probably have a positive impact on life expectancy but it you know it's going to be affecting the life expectancy by hitting the people that are dying earlier and pushing them more toward normal.

Yeah. Whether it pushes normal further or not as we discussed is still an open question. So.

Yeah. Yeah. And I hope just like you know sarcopenia rates don't just like start.

Yeah. Um, I I've asked like 20 doctors now, uh, do GLP1 agonist accelerate muscle decline faster than other weight loss strategies? And I've got 20 different answers.

Is there any grouping that you like is.

Well, I mean, I most doctors will at least say that anything any strategy you use to lose weight, diet, metformin, they will cause loss of muscle mass. Uh, and so you need to complement that with things that increase muscle strength. Um, for people that are not psychopenic already, that's exercise. Even for people that have psychopenia, exercise can probably help. Um, but in terms of whether you lose proportionally lose muscle weight more with GLP-1 is I don't I haven't heard a consistent answer yet. So.

Yeah. Yeah. Yeah. I mean, I wonder how many doctors are actually measuring the muscle loss on.

Yeah, they should be because, you know, if if if you go from obese to, you know, less obese with less muscle, I don't know how much better that is. So, muscle is highly protective.

It's metabolically protective and certainly strength protects you from a lot of other complications with aging, too. So.

Yeah, I I agree. Um, do you think these GOP ones are things that people are just going to be on for the rest of their life?

Um, depends on the person.

Yeah. Um, you know, I think that the problem is a lot that people go off of them and then they gain weight again, you know, and so. And they don't add on a lot of the muscle that they. And they don't add back the muscle. So, it can be worse. Yeah. Um, maybe they they may be, but that's still probably better than at least for people that were obese and had poor metabolic health, it's still probably better.

Okay. Yeah. Let's talk about peptides. Um, super controversial. Feels like they just became ultra uh exciting to people like relatively recently.

Yeah. Um, what do you what are your thoughts on peptides? Then there's some legislation change that I think we're going to get a bunch of peptides back now.

Yeah, I I look, first of all, the promise of peptides has been totally underappreciated. Let's look at some of the insulin GLP-1. Yeah, these are effective drugs. And this is just the tip of the iceberg. There, you know, 20 thou 20,000 50,000 proteins in the cell depending on how you define one distinct protein from another. um there any of those proteins could be parsed into small peptides. So there's almost an infinite collection of different peptides to use and we haven't done enough research on them. These are active molecules. They stay in the around in the body. They do things that the body makes them to do things. You're just augmenting that, you know. In some cases you're using peptides from plants and stuff too I realize. But these are natural things in the body that are have activity. So the promise of peptides I think is tremendous and unfortunately most of the research has been done in in places that didn't have the resources to really test them. So and and the big challenge right now is I don't even you know we we're just doing a LLM based screen for drug for peptides that are likely to affect longevity. And first of all we found over 200 peptides that have been linked to longevity in some way or another in the literature. U but the amount of research on them is for the most part I mean there are excluding GLP-1 and stuff the amount of research on them is extremely small. So um we don't have enough knowledge to know which peptides are are doing that but I think that field shows a tremendous amount of promise. The other challenge right now is where you source your peptides from.

Yeah. You need to get them from some place you trust that can make them and and usually they're injectable. Um there's some peptides now that are being developed for oral delivery, but I still think that science is even more untested than the direct delivery subcutaneously. So.

Yeah. I I'm worried about safety. I mean, so I think you need and I think most of the safety probably comes from contaminated material, not from the peptide itself, but that's a big concern. And and um and then we need more data to figure out which peptides are having the biggest effect on aging. I'm very confident some of these peptides are are likely to be working, but I'm not willing to make bets on specific things right now because there just isn't suffic there's not sufficient data. And one of the things we're thinking about in our lab, even in the pre-clinical setting, is to to focus much more on peptides now because there's a lot out there we that's promising, I think.

What are the LLMs identifying as the top potential longevity peptides?

Yeah, well, we're just working through that process right now, so stay tuned. Okay. I can't even tell you because I haven't seen the latest data. We're not We're getting different iterations of that data, but we're not at a level of confidence yet that even I believe it. So.

Okay. Well, you'll have to let me know. Um, have you ever tried a peptide yourself?

Yeah. Um, I uh see I tried I had a really bad viral infection. So, I took uh I think it was BPC. Okay. And 157, I think. Okay. And then a couple other peptides in combination. And it reduced uh.

Diamond and alpha was that another.

Yeah, that was one of them. And it reduced um uh my uh it didn't stop the virus but it reduced the the the side effects, you know, so I got less um nausea and uh things like that almost very quickly. So yeah.

Um, I've been doing peptidism on and off for I don't know seven eight years always doctor prescription compounded at an FDA approved facility. That's the key, I think. I mean, I've been offered so much, you know, so many so much money by like these gray market peptides and I'm like, absolutely not. I don't trust it at all. And some of them are probably fine. It's just really hard to know.

Yeah. Yeah, exactly. I mean, unless you do your own independent testing on them. I mean, you just don't know. And it's I get again, I I fear about that for safety. Actually, a huge one of those companies.

Yeah. Now that you know, it's been announced that those 14 peptides are coming back. Yeah. They've shut down now. It's interesting like Peptide Sciences was the biggest one. I've never ordered anything from there, but they've been like historically know that. And they're shut down now.

Um maybe they feel like they made all their money and they're just good for who knows. I don't know the story.

Um but I will say so when I did all my international travel last year, I was taking thy Alpha. And I did not get sick one time. I was really astounded because all those planes, all those people, yeah, time changes, lack of sleep, all that. Not even a single time. And even when, you know, my husband and everybody else that I knew was like ultra sick. I didn't get sick. I mean, it's just end of one, but um there was that. And then I um at my old house in LA, I smashed my finger in this like ultra heavy door. And I started injecting BPC into my hand and it it fractured. So I had an X-ray that it was fractured. And two weeks later from doing that injection, it was like I mean, not only did it feel great, but it also looked great on the X-ray. So like that's pretty crazy.

No, that's I mean, that I think that we don't we're we should pay a lot of attention to these peptides and and we're trying to work much harder to you know, figure out which ones to test for which things and and really how do we get real meaningful data on mechanism and and uh credibility to improve credibility because look I think they're going to be as good as drugs and and we've just ignored this for the most part relative to drug development.

Absolutely. What are your thoughts on gene therapy?

Also very promising. I I'm not supportive of doing it now because I'm not sure that the technology is there yet to to to cause an effect. I mean, certainly gene therapy. Yeah. The funny thing is that when I was in the eighth grade, I decided I want to be a molecular biologist. And uh probably a bad time to make that decision. I mean, it turned out okay, but but I read this book on gene therapy. So that you know so that was you know 1980 and uh it was it was going to change everything and I'd say only in the last 5 to 10 years do we have effective gene therapies to treat sort of rare childhood diseases and stuff. And so I think we're on the steep edge of the of the learning curve now or not the learning curve but maybe the the the usage curve for gene therapy but still at that early stage. And you know, you can make a case for talres. You know, I Liz Parish is a good friend of mine.

Yeah, she was great.

Yeah, you can uh make a case for um the muscle fallatenistatin. I think, you know, they're interesting targets. Uh but I'm not sure that phosatin is going to extend lifespan. And I just I'm not convinced that they're that efficacious yet. So I supportive of the concept. I want to see it develop, but I'm not encouraging people to go spend a lot of money doing it yet. So.

Yeah. Yeah, that was one of the things I'm always gauging risk and reward, and that was one thing that I decided to definitely hold off on because I mean, number one, I haven't had kids. Number two, I'm 35. Like, there's a whole bunch of reasons, but.

Yeah, it was curious to hear.

Yeah, I kind of feel the same way. And I I also think there's a huge uh uh rejuvenation uh stem cell rejuvenation therapies I think are are very promising and and they have the potential maybe to have even bigger effects than the other things we've been talking about. But how how easy it is to develop that into a safe therapeutic approach I think is unclear yet. But that that concept I think is very interesting. And do you think well number one curious any sub type of stem cells that you're most excited about whether that be you know.

So yeah, so that's a so this is sort of reprogramming I'm talking about. Okay. But we I'm happy to talk about stem cells too.

Well, first let's talk about the reprogramming isn't there something did something major just happened I haven't read it but you know there's specific researcher that something yeah I think something just happened with cellular reprogramming that it was a big deal but I haven't seen the latest studies I you know I think that the challenge is how do you reprogram cells so that they are you know promoting youth again repopulating tissues without being can carcinogenic on their own um or and I think that we just don't know how hard that's going to be you know when it's the same way with synolytics right so like 50 years ago we said oh even more than 50 years ago we said cancer cells are different than normal cells. If we can just exploit the differences with cancer cells, we can kill the cancer cells and leave the normal cells and we'll cure cancer. And so, and over the years, we've declared war on cancer. I don't know how many times now. Um, still have cancer. Uh, it's not that that concept is bad, it's that it's really hard to specifically target cancer cells and not harm normal cells. I mean, don't I don't want to criticize the field. We're much better at treating cancer than we were 50 years ago. People live with a lot of different cancers they would have died from now. So I'm I think progress has been made, but it's hard is what I'm saying. And so then when you say we're going to kill scinsesscent cells and leave the normal cells, the scinesscent cells are probably closer to the normal cells than the cancer cells are. So it's an even harder question. Got it. And then when you say we're going to reprogram the cells um so that they're younger but they still function normally and are not don't lead to cancer. We don't know how hard that's going to be but conceptually I think it's great and if it works it'll could dramatically impact aging. I think now there's stem cells you can get today too. That's a different question. I don't know if you've tried that yet. I've had MSC's IV a couple times. Uh.

Yeah. Yeah, I've done a couple. Um I am and I also banked my own stem cells. So had that derived from fat and then they've been multiplied out and then I might use that as like I don't know just general IV for myself. I'm more Yeah, I would love to hear your opinion really quick to go back to the reprogramming. But then you would have to reprogram the cells in every single organ, right? Like what.

That would be. Well, we know how to reprogram cells. we can make IPS cells and so the the question is how do we do that in vivo in an organism in a way that's safe and uh there are lots of strategies to do that there gene therapy strategies there uh drugs that mimic the effects of the genes that do the reprogramming people are developing uh so uh it's early days right now you probably don't have to reprogram every cell you know if you can reprogram some cells in a tissue you may get a lot of benefit from that so um so You know, tissues are good at rem remodeling, some better than others. I mean, like brain has a very low turnover, but but other tissues turn over relatively quickly. Um, and you may not need to fix everything. You may just need to fix enough to get back over a threshold and then the the tissue can autoregulate itself again. So. So um we all interesting questions. I think that's a fascinating area of research.

Um, yeah. Yeah, that's definitely exciting. To go back to the stem cells that are kind of available now, um what I mean, do would you think those have promise as well for longevity?

Yeah, I I haven't seen compelling data that that systemic MSC's uh slow aging. I I can believe it might happen. I they're certainly anti-inflammatory. Um but I I haven't seen data that I think is really robust yet. So uh optimistic but but not convinced yet. Uh question is same same issue with the peptides. Where are you getting the stem cells from? Are the stem cells really good? What's the source? You can get them from umbilical cord. You can get them from your own bone marrow um or your own atipose. Uh these cells are they're not all exactly the same. They're similar. Uh and which ones are going to be more beneficial? Well, is it better to get stem cells from the umbilical cord of a baby, you know, that are young, or is it better to use something from your own body? Um.

Yeah. I I hear a lot of again, it's a lot of noise and not consistent opinions on that. Also, there are a lot of different isolation of stem cells now, these very small stem cells and other kinds of stem cells, and those are just emerging, and they may be better than than MSC's. So um then there's you know ENK cells and other things that people are doing that I think also are promising but again a lot of this is happening in places where there's not enough resources to get the real data so people believe it and they're marketing it and but I can't point to studies that say yeah this definitely works. I think the first principles it makes sense.

Yeah. Yeah, I agree. I mean, and I guess placebo also is like a real thing. So maybe.

Placebo is real. Every study we do, you know, whether people get the pill with the with the active ingredient or not, they get better. It's I think aging is very and and in a way that's a positive thing, right? It's telling you your aging is influencable. Yeah. You know, your mindset has a big effect on your age. And you know, we haven't talked about psychology and and and mental mindset and and other kinds of drugs that may not quite be legal, but I think some of these things are probably good.

Uh oh, yeah, the psilocybin. What are your thoughts?

I think the data is really strong on psilocybin. There's animal data. It's not the best animal data. There could have been more mice and stuff like that, but it extends lifespan in mice. It looks believable. Um there's a lot of data on PTSD and on on uh depression, hospice care for and and the interesting thing about it is single dose tends to have a longlasting effect and there's data that these drugs cause synaptogenesis. Um so it sort of rew helps rewire your brain. So I I I think we should be doing a lot more research on it. You know, we've this is another example, right? We took a set of drugs and we classified those as illegal and dangerous and some of them are dangerous.

Sure. But you know, psychedelics got put into that group. Uh whereas I think there's a lot of therapeutic benefit from psychedelics and uh um we should maybe stop siloing molecules and start thinking them more holistically and and uh I don't know I I think that's a very promising set of drugs for longevity.

And why why is it good for longevity?

Um I think it it reduces anxiety in a lot of people. Yeah. And not not just short term when you're taking it, but over a period of time. I think it allows you to see the world differently and be more accepting of the world you're in and and uh integrated with it. I think that I think that's one thing. It if it creates synaptogenesis, that could be good. Uh and there are other potential benefits as well. But even mice, you know, mice are very have a lot of anxiety as they get older.

Oh, really?

Yeah. It's hard to measure, but you but you know, it's like you can sort of see it, you know, you can sort of measure it by the time they spend at different parts of the cage. Are they out in the open exploring things? Are they huddled in the corner? That sort of thing. Uh, and so even in animal models, I think things like anxiety are important. And so, and we haven't paid enough attention to it. uh a lot of you know a lot of people say that you can control a lot of your health by your mental state and I think there's some truth to that and psilocybin may be helping people get there.

And the dosages for people doing that that seem to have or in the mice models it's a large dose right now like a micro dose over.

Time. Yeah, and a lot of the human clinical trials are are larger doses sporadically or even single dose. Uh I I don't haven't seen much data on micro doing Um it's uh may I maybe I missed it but.

Yeah, I haven't looked at that too much. I'm kind of neutral to that. I don't know you.

Yeah, that's something I have not tried but maybe. Yeah.

Well, yeah, there's always a first time.

Yeah. Have you tried this?

Uh possibly.

Okay. Okay. Um well, I mean, no, that's super exciting and it would be I think everyone could benefit from less stress and less anxiety and trying to like rewire the brain.

Yeah, I mean, like any drug, it I think it you should do it with a qualified guide.

Yeah. Yeah. Uh because there are bad trips. I don't think there's a lot of risk biologically to them, but but you can have bad trips from them. And.

And how long does How long is a trip?

Well, you I we're getting down a path where my uh not sure how much I want to be an expert. This is outside of your expertise. depends on the dose, but they're they're they're interesting books if people are interested on psychedelics and uh um there's a lot of information out there and uh you should uh do it in a controlled way.

Yeah. If you do it, I'm not advocating.

Yeah. Well, I mean, hey, if the data is so strong, I mean.

I would Well, I am advocating for more research and control trials because I think there is a huge amount of potential.

That's amazing. Um should you go back to a basic thing real quick? exercise. Um, what type of exercise is ideal for longevity? Uh, highintensity interval training, strength, both.

Yeah, I this is a a minefield, too. Let me start by saying that it's not just endurance or not just resistance. You need to be doing both. And um but uh I think that you can wade into that pool or go to the deep end. And it's a it's a real challenge to figure out where to be. I like doing interval training personally um because I feel like it really improves my cardiovascular parameters and my endurance performance and so I hate doing it but I have so I hate doing treadmills so I I like to run outside and I also hate doing intervals. So now I just I realize that hate squared is not more than hate. So when I'm on a treadmill I do intervals.

Yeah. But when I'm outside I run distance. Uh.

So that that works for me. Um are you doing like a 4x4 kind of situation?

I I try different strategies, you know, I try to do four or five minutes at a high speed, which you know, I I run 8 to nine minutes a mile when I'm doing like a 5K. So, so then when I I try to elevate 10% above that or something for four minutes and then I I walk, you know, at like a brisk walk and just oscillate back and forth between those two. I'm not sure that's optimal for me. I'm comfortable with it.

Okay. Um I think comfort is really important with exercise. It has to be something you're comfortable with. You know, suboptimal that you do regularly is better than optimal that you don't do.

Yes. Absolutely. Um the other thing with resistance training, you know, I had never really gotten weight training lessons and uh it's funny. I went to uh started doing this about five years ago and I've definitely added muscle mass doing it. Great. So, it's good. But, you know, I went to one of this uh uh fit high level bodybuilder that has a fitness gym in Singapore. She uh came to one of our conferences and she said, "I want to figure out if we can work together because," you know,

Even if you, if you go to a fitness center, if you don't know how to do the training right, you're not optimizing." Even the people that are training you there, if you hire a trainer, most of them don't know what they're doing. And, yeah, and so I'm like, "All right, I'll do it. Yeah, I'll come to your center and and do this." And so I've just started doing this. And it's like relearning.

I I'm not going to be in any bodybuilding competitions and that's not my goal, you know. But I don't know if bodybuilding competitions are optimal for a long time. I am not sure either. That's, uh, but I think that when they look at me and and they're not trying to do this for that. They're trying to take middle-aged people and get them strength that's going to help them maximize their benefit as they get older. So, they look at me and they're saying, "All right, you you have muscle mass, but you're asymmetric. You're hunched over. You know, you're you're not training the right muscles. You know, you and I focus on core, but they're saying you're still not training the right muscles." So, yeah, they're like retraining me and like everything like the low row thing, everything. They're like retraining how I do it. Get the body right move.

Nice. Yeah. And uh, it it I just started doing it, but already I can feel a difference. Yeah. So, I I think that really going out and finding, if you really want to do it, finding real expertise that people that know how to do it is very important. You probably get benefit from doing it suboptimally as well. But, you know, it's worth uh learning. It's worth really becoming knowledgeable so you know what you're doing. I think that to maximize your benefit and, yeah. So, I'll let you know. But it's we'll see if I'm straighter next year. You see?

Yeah. I I love that. Yeah. I mean, it's all these like little tweaks over time, you know. Yeah. I feel, I but I think it's kind of fun and I think you I'm sure you feel that way, too. It's fun to like learn about things and make changes and see benefits from it. Yeah. It's I mean, the best.

So, out of all the things we kind of discussed today or anything new, I mean, what are you most excited about in the future of longevity? Um, I I think what we're going to see in the next few years is that really strong validated evidence we can modify aging and it may be small effects, like we have some a study coming out uh showing a very small effect with uh uh AKG, but it it's good solid study, right? And I think that's going to really help um get more widespread use. I I want to see all of medicine thinking about aging just a tiny little segment of it and and so that I think that'll help. The other thing is biologic aging clocks, like the one we're developing, that can be put into a medical practice and understood by doctors and used to create actionable outcomes. I think that will help the field gain traction, hopefully.

Yeah. Yeah. Um, so, you know, it it's funny. 10 years ago, nobody was talking about aging. Um, or maybe 15. Um, and now there's this explosion and and I love working with the longevity clinics and everything. Um, I think they're really the most of them are do trying to really do cutting-edge approaches to help people. There's some things pe some clinics are doing I don't really support, but generally speaking, I'm supportive. Mhm.

Um, how do we take that and put it into mainstream medical practice? I think that's the real challenge. Yeah. Because I I want to see the population numbers change. Yeah. Yeah. And, uh, I'm happy if people that can afford it have a big effect. That's great. But, uh, I want to see the population numbers change. And so, I'm thinking about the things to get to that stage. You know, I'm I'm like, it's funny. I'm 59 now. So, um, I think of myself as immortal. Not not because I really believe I'm immortal. I just like the mindset it gives me. I don't worry about the future. I just I I if I if I see something I want to do that's going to take 10 years to come to fruition, that's fine. I'll be here. I'm still researching in 10. You whether that's true or not is almost irrelevant. It's the mindset I get from it that I think is so beneficial.

And that's been that's been proven out in research too, right? Yeah. I had to I had, you know, I've had a lot of things happen to me. You know, I had a major birth defect that created a lot of surgeries. Oh, wow. Then I got in a car accident at 22 that um also uh led to a bunch of surgeries and broke for 14 bones and tore my nose off and all head to toe problems. Uh, and uh, so I you know, living through those things changes you and not always for the worse. I think the especially the car accident, it changed my mindset. I went from being more introverted and and worried about things to like realizing that, you know, I'm going to try to do what I want. If I fail, trying to do what I want is better than not trying to do what I want. Yeah. As soon as I took that mindset, everything became easier. And over time, I've, you know, had stressful periods that I've had to deal with. And, you know, I I may get sick tomorrow. Who knows? But but I think that what I've tried to do is find a a path that I'm manage my stress, try to be healthy, try to enjoy life, work hard, but still enjoy life. And uh, I'm getting better at it. Maybe I'm not great yet. So.

Well, I love that. We didn't talk too much about why did you move from, you know, you obviously you were at the Buck and then you went to Singapore. What was the compelling? I think the mindset in Singapore toward healthy longevity is is really good. Um, even when I was coming there, they were already saying, "Oh, you know, we're only going to have four workers for every retired person or two two, sorry, in five years, two workers for every retired person. 30% of the population is going to be over the age of 65. We're a small island. We can't just take more and more immigrants because we're running out of space." Uh, so um, what do we do about it? And uh, the idea of keeping people healthy longer was in the mindset when I came in 2017. So I could move to a world-class research institution, you know, in US is always in the top two ratings in Asia uh for universities uh that has great medical school, good clinical studies. I could take my research from preclinical to clinical um and also um a government that's progressive minded. Now they're a bit risk-averse at times and so only now are they really committing a huge amount of money to to sort of research on healthy longevity. But they have a new program called RA 2030 where they're going to put 350 million Singapore dollars equivalent about 300 million US focusing specifically on aging and keeping people healthy. Uh, and you know, and not many governments are doing that. So it's a good place to be doing longevity research. It's a supportive environment.

It's a small island and so if you develop something you could imagine it being instituted in a whole population and yeah making Singapore sort of a model for keeping people healthy and functional as long as possible. So, I'm happy to be a part of that. And and uh, you know, also Singapore is a really nice place to live. It's it's super safe. Uh, and uh, great food. You know, it's a good place to be.

Yeah. Where where do they land on the like longevity spectrum or span spectrum? Uh, in terms of lifespan in Singapore, it's it's in the top three. You can argue between top three, Hong Kong, Japan and Singapore, but lifespan is life expectancy is already in the mid to higher 80s in Singapore. Much higher than us. Goodness. And it, you know, it comes back to having a good healthcare system. Yeah. Um, something that the US has a good healthcare system if you can afford it and you have insurance, right? Yeah. But if you can't, you know, you're in trouble. And um, Singapore has a good baseline. Everybody gets a certain level of healthcare and it's I it's not perfect. There are things I don't love about it, but generally speaking, it takes care of people. And um, they benefit from that. I think the diet's better in Singapore. Yeah. Uh, it's better everywhere in Asia. It's probably better everywhere than US, right? Yeah. Like the absolute worst maybe. I don't even know. It's not ideal in Singapore. There's certainly challenges in the diet, but it's healthier and so and and the government cares about its population. I it I don't agree with everything any government does, including Singapore, but I do believe that they actually care about improving the health of their population. So, that's a good place to start. That's Yeah, that's a great that's a great starting spot for sure.

Yeah. Yeah. Um, well, one ex I mean, I've heard that now nutrition is going to be taught in medical school, so maybe that's one step forward. What about aging? You know, it's like I how can the one thing that happens to everybody that walks through the doctor's office not be taught in medical school? It's incredible. It it just shows you how slow things are to change. And um, it's a mindset issue. I But trying to change curriculum in medical school is a Yeah, I'm not sure I want to die on that hill. It's hard. I'm not an MD either. I'm a PhD. Yeah, but um, yeah, nutrition is a good start, but there should be like a whole course on aging, you know, because it underlies all the pathology that you talk about at medical school and and and it's still being ignored most schools.

I mean, also from what I've heard, you know, menopause is like not even discussed whatso. It's like, yes, this thing happens, but there's no education as to why or how or what or anything as it relates to you know, things just become systemic and and and unmodifiable. You know, the fact that we do sick care and not healthcare that you can see how that developed and and it at the times decisions were made, you can see why the decisions were made, but now we're in a place where we know it's not the right strategy. Obviously, when I get sick, I want to be treated, but I'd rather not get sick. And and that's what we should be focusing on. Yeah. But once systems get entrenched, they're really hard to change. And uh, you can talk about that from the perspective of the NIH or from insurance companies or hospitals or or pharmaceutical companies. And all of these places are full of well-meaning people. Yeah. But the system is like set up so that they're it's not optimized to keep people healthy. And I you know, I guess we one of us needs to be made king for a day and we can fix it. There you go.

Did you there was that recent woman that passed away who was you know like I believe a super centenarian? Oh yeah. Did you like was there anything interesting there that they found? I didn't I don't know which one you're talking about. You know the uh um the the longest lived woman of course was Jean Kon although there's a lot of controversy about that but if you believe the birth record she was 122. Yeah. And so generally the the oldest lived person is somewhere between 116 to 119 and almost always women. Yeah. Um, and uh, the uh, but I don't know the specific one you're referring to. I I will tell you one story though. I was uh in Nicaragua and just on vacation, some remote area and uh one of the people there said, "Oh, well what do you want to go horseback riding?" So I'm like, "Yeah, sure." They said, "There's a woman with a farm outside the outside the little town we were in that has horses. We can go there." And they said, "She's American, too." So, we went there and and we got on horses. And and I'm riding with her. And she's saying, "Oh, what do you work on?" I tell her aging. And um, generally when you tell somebody you work on aging, they always say, "People in my family live forever." You know, my grandfather was 88. And you know, yeah, sometimes I don't tell them. I do that for that reason. Anyway, she said, "No, there's a a man in a little village, one of the farmers that's 105. Uh, and do you want to go say hello to him?" And um, I'm like I'm like, "This is highly unlikely, right?" Yeah. I'm not even sure there's any 105-year-old male in Nicaragua right now. And on top of that, the fact that I would be next to them is very, very unlikely. But I'm like, "Sure, sure." So, you know, we go to the his house and he's got it's like one of those westerns. You get off the horse and you throw the the rope over the Yeah. over the over the little wooden log and we walk into the house and he was on a bed and he was um not couldn't see well or hear that well. Uh, and she walked up to him and said hello and he took her hand. He's like, "Oh, gringo." Cuz she has big hands. Oh. And so, uh, so I started talking to him and, you know, I'm asking him questions that to what I know to see if he, his answers are consistent with being 105, but I don't know my Nicaragu. So, but anyway, the questions I was asking, he was giving answers that were very consistent with that, and he was very clear-headed, actually. Um, and so, finally, I said, "That's possible. Maybe he is 105." So I said, "So what's your secret to being the 105?" And he's like, "Wife 38 years younger." Oh, wow. That was So I don't know if that's the I'm not advocating that behavior.

I mean, yeah, that's interesting. So, do you did you land on you think he's 105 or uh, there's I mean I I wasn't in a position where I I mean I'd have to go back and get like medical records and exactly in countries like that especially at that age you know it's it's really difficult even in China you know we I was a one of the editors and chief of aging cell for a number of years and so we're publishing papers on aging when they did studies on centenarians in China it was a challenge because you know when they they didn't go to modern calendars uh until you know 40s maybe. So people that were born before that they were using Chinese calendars and we had to hire experts to like look at the birth records to even get a good estimate on when people were born and that China has better records than Nicar. So you know it it gets hard to really validate people's ages.

Well, the whole blue zones thing kind of did that like fall apart a little bit or I I think I think that some of the data is more aspirational than real. I I do believe Okinawa was a blue zone and uh it was really an interesting one because um that was the poorest prefecture in Japan. And yet it had longest lifespan. That's extremely rare. Usually the wealth is associated with longevity. The zip code get determined for longevity like in the US. Yeah. So, uh, the uh, so there was that was really interesting. Of course, the current generation of people in Okinawa are not long-lived anymore. And so there were behaviors that a lot of American military bases and influence and stuff doesn't help but it's also not a wealthy prefecture. And so the uh um, but there were definitely traits in behavioral traits in the older population uh that suggest that they were doing things that made them live longer. So that research is really interesting. Some of the other zones I certainly people lived long in those zones. Whether they live clearly longer than people around them or is more debatable. And then what they're actually doing that makes them live long I think is still a little bit unclear. So it's easy to jump to conclusions Mediterranean diet but people in that whole region eat that diet. You know, the um um, you know, social connectivity and the people in California because of the religion um that those are plausible explanations and in many cases I'm not convinced that's the only reason or the real reason. So, yeah.

Well, in Linda too, I think they're like not they're not drinking alcohol. They're not doing they're not doing so many things that it's probably hard to like really Yeah. And I think the overall effect on of alcohol is bad because too many people are drinking too much. Whether there's a modest benefit for some people drinking a low amount is a different question. But the population size effect is probably bad because the negatives in people drinking too much are really high.

Yeah. What would be the positives? Because it it was thought to be like resveratrol or something but then obviously I've never believed resveratrol because you can't get enough res you'd be like almost dead. And also I'm actually we published a paper that said that resveratrol doesn't activate cert1. So I I have a long history of arguing with people on that. Uh, it may be beneficial. I just don't think it's through certuins. Um, but anyway, you're not getting there are a lot of different kinds of polyphenols, by the way. So, when you when you drink wine, you're getting many different kinds of polyphenols in very low doses. Um, ethanol is good for you for your cardiovascular system. I still believe that to be true. Um, what I tell people and and you know, everybody has an opinion on this and and you can cite data supporting or arguing against a lot of different things. My belief is that low dose of ethanol consumption is probably beneficial or or not harmful for people that um don't have addictive behaviors, don't have breast cancer, prostate cancer risk um and that can manage it and and uh um, but you know, a lot of people fall outside of that category. And uh, if you fall into those other parameters, you probably shouldn't be drinking at all.

What do you define as low intake or one to two drinks a day? Okay. Yeah. And and not binge drinking. That doesn't mean 10 drinks once a week. Yeah. Stacking them all. Yeah. Binge drinking is I mean you can just look at your HRV if you don't believe binge drinking is bad. Oh goodness. Goes through. If I drink too much in a day, it my HRV is like goes plummet.

Well, sleep score too, right? Yeah. Everything plummets. Yeah. Yeah. Absolutely. So, uh, but you know, there's so many people that have, you know, reasons for their opinions that alcohol is either bad or good that I I have a hard time parsing through all the data and every five years it goes back and forth. So, it's Yeah. The other thing I should say is that alcohol is calories and it's pretty meaningless calories. So, that's another thing. If you're overweight, have have, you know, metabolic issues, you're you're throwing in a lot of calories, you know, from a glass, even any kind of alcohol, basically. Yeah. Even ethanol is a source of calories, you know, directly. So, it gets converted to energy at some rate.

And why is ethanol good for cardiovascular health or could be good? I don't think it's entirely clear. There's some data that that that's there's a lot of data that's epidemiological that says it's beneficial. Okay. Yeah. Um, h what would you say um if you or or tell us about your your day like if someone wanted to have like a longevity day how would they do that? My day I have no pattern to my day. Okay. What could a long day when I'm in Singapore and not traveling? Yeah. Um, especially like on a weekend where I don't have a meetings all day long. And the big problem with Singapore too is that you're I have a lot of collaborations with people in US and Europe. So I'm up at 2 in the morning and stuff a lot. Um, but you know, I I generally I'm not an early morning person. Okay. Uh, I know people love getting up and exercising early. I can't get past the coffee and then when I have the coffee, I need an hour or two before I can really do serious endurance exercise anyway. Um, so, uh, but I I try not to eat much during the day and, uh, you know, I'm not religious about it. I'll have coffee and, you know, I may have a small amount of food in the morning, but very small. And then I have a larger meal later in the day.

How's later in the day? I eat pretty late, like seven or eight. I know. I know. Don't tell me. I'm done eating by 4. Yeah. I I eat a lot of co I drink a lot of coffee. I don't see the data on coffee is pretty good. I think if it's if it's not keeping you awake at night and it's not you don't have certain kinds of cardiovascular problems. I think coffee is probably the more the marrier. That's what the data suggests anyway. Um,

Do you try to do like you know lab tested coffee or anything like that or like you know Yeah. I'm not that picky. Organic biodynamic anything like that? Yeah, I get organic stuff when I can, but I'm not that picky about it. Um, I try to eat um diverse, you know, and that's easy to do in Singapore because you can there's 20 different kinds of ethnic food you can get at any given time. Uh, some's healthier than others, but I try to eat very broad and diverse and try to balance my my micronutrients. I try to do some form of exercise every day. I mix endurance and resistance training, but at least something every day. Even if it's 20 minutes, something. Yeah. Um, I'm focusing more. I'm really bad. I realized that I Somebody took a video of me hitting a golf ball. And I I strength-wise, I'm pretty close to where I was when I was young. And endurance- wise, maybe even better because I do a lot more effort now. Yeah. But I realized that, wow, I look like an old man. I have no flexibility. So now I'm going back and working on flexibility, balance and things like that, mobility, things like that. Yeah. Um, so that's something you can do at home, like one of those balance balls and things like that. There simple things you can do. Yeah. Um, yeah. So, uh, and then but I I like unpredictability. I don't like a routine. And I know that may not be the healthiest thing, but I like that in my life, by the way. I I don't want to know what I'm doing six months from now. you know, it's Yeah. Okay.

Well, I mean, yeah, definitely the the bones are there. Um, it's so funny because we kind of have like some opposites like I'm in bed at the same time every day and then I'm done eating at a specific time. Um, do you have any thoughts on So, I do a test called the micronutrient test. I do it like four times per year and that's how I determine my supplementation for the most part. That's interesting. I haven't tried that. No, that I should do that. You should tell me that where to get that. Yeah, you should do that cuz I'm curious. I mean, I think it'd be safe to assume if you're running, you know, not micronutrient deficiencies, but insufficiencies for long periods of time, that probably wouldn't be I I measure things pretty regularly. I just haven't done that test because whenever I go to a longevity clinic and work with them, I tell them, "Put me through whatever you do." Oh, good. Yeah. Because I I partly selfishly, but but also mainly because I want to see what they're doing. And I think if you see it from a client perspective, Yeah. It's different than if you just get a list of you get a booklet about what they do. I think that's less meaningful if you actually go through it. You learn things and and different clinics do different things. One of them recently they did a rectal ultrasound. I'm like I'll be happy if I don't get that again. Well, is that like a prostit like Yeah. Um, uh, but you know, I so anyway, I'm pretty well tested. Yeah. Yeah. I do it with um, I mean I've done both Vibrant America and Gova, but I like it because it'll look at um, you know, cellular and serum. So it kind of gives you an idea like are you burning through more nutrients? Are you getting enough from your diet? And then I will amend the supplementation or food. I try to do fruit food first. So like I think last test I was a little low on vitamin C. So I introduced some more citrus fruits but also did you know, I think that's good. By the way, I I think one thing that's low-hanging fruit that we do not pay attention to generally is vitamins and minerals. You know, we I again, it's a part of the industry, right? People want to sell pills. Yeah. They want you to take a multivitamin. What we should be doing is optimizing our vitamin levels, not just taking random vitamins. Yeah. Uh, and um, I think I I would bet that if you could optimize vitamin levels just that you would enhance your health span by 5 to 10 years and and but you know, we argue about what optimal range is. We we uh, and companies that sell vitamins don't want to measure in people and optimize. They just want to it's easier to sell pills. Yeah. Um, and so I I that would be something I would change. It's like let's pay serious attention to these vitamins and also other micronutrients and say let's get this right. Particularly B complex by the way I I we continually see people that are low in B complex we by biomarkers they appear to be aging more quickly. So that's something I would pay a lot of attention to.

I mean I would guess if you did a micronutrient test right now on you know almost any just average individual it would be a complete disaster. It would be low on everything. You know what I mean? A lot of things certainly. Most things. Yeah. I feel like um Yeah. Yeah. Because the number one consumed vegetable here is like um potato chips or whatever. Like and fries or something. It's absolutely crazy. I grew up eating a lot of fast food and u I have to like uh I'm still addicted to it. I I have to when I drive by I have to like I am not turning. Oh my gosh. See, I see it as poison. So I like zoom past. I'm like that is like not even a to me that's like not even food anymore. pretty much don't eat it, but I still crave it, you know? It's like I still fight it. And potato chips, too. It's like I don't let them in my house, you know. I won't say I never eat them, but it might be twice a year, but I they don't come in the house.

Well, I feel like I forgot what a lot of things taste like. And I'm just I want to keep it like that. People are always like, "Oh, just have a tiny bit." I'm like, "Why would I have a tiny bit of that food that has been engineered to be hyper palatable and then I'll crave it later? Right now, I don't crave it cuz I don't remember what this stuff tastes like." Yeah, I agree. A simple example of that is like people that switch from Coke to Diet Coke. You know, when they first start drinking Diet Coke, it tastes awful. They don't want it. Mhm. Like three months after they You probably don't drink either, I know, but bear with me. Three month three months after you've switched to Diet Coke, the regular Coke tastes way too sweet, right? Because you've recalibrated your taste. And yeah, it's it's such a real thing. I mean, to me, like a sweet treat is, you know, a handful of blueberries or some cherries or something like that. I quit eating. I almost quit eating very sweet things too. And uh, I I've uh, I've stopped many years ago I stopped and growing up we added salt to everything. I quit doing that and then flavors came out, you know. It's like I would I can't I don't even think of adding salt to things now you so it's uh I I'm trying to make I'm not as good at diet as you are I'm sure. I'm trying to make changes that uh and I I can see that I'm adapting to it and yeah, I eat a lot more vegetables than I used to, you know. And u also, you know, growing I grew up in Kentucky, you know, it's they could take any healthy food and make it unhealthy, you know. Right. Yeah. Take okra, you bread it and fry it. Yeah. Yeah. My grandma would take a tomato and fry it and then I'm like, why did we do that?

Where'd you grow up? Ohio. Oh yeah, I was in Louisville. So Okay. Yeah. Not not too far away. Probably not too different of a mindset either. Seven layer salad land. Yep. Exactly. So, um, but you know, I feel like I was able to overcome a lot of that, you know. I mean, I was on a lot of antibiotics as a kid and like all that sorts of stuff. And we now know that like what it can do to the gut microbiome and but by really following these regimens and having a lot of testing, I've pretty much seemed to remedy it. I have to do I have to eat a very different diet too because my colon didn't develop. That's the birth defect I had. So I have to be careful with fiber. Okay. Yeah. Too much fiber is makes it feel like I swallowed a soccer ball. So I have to my my ideal diet's a little different I think than most people. But I try to get as much fiber as I can that doesn't make me feel miserable.

Yeah. Yeah. I mean well fiber in general is another one that is so you know unconsumed here. starts like crazy. Yeah. Yeah, I agree. So, and well, is there anything else that you think people should know about longevity or No, I I don't know. Leave leave people with the message that the time to take action is now and you can be conservative or you can be on the edge, but doing nothing is harming yourself. Yeah, I agree with that.

Well, typically at the end I ask people, you know, where can we find you, but do you have social media? Yeah, I do have social media. Uh, do you post anything on it? I followed you, by the way. I post, but not that not that much. So, okay. Wait, maybe. So, I need to make sure I'm following the right one. Yeah, we'll get connected and but I'm on LinkedIn and I know that's like our cake. Do you want to drop a website or anything where people We have a website for our healthy longevity program and we also have a new website for our consulting company, Live Beyond, and it has a lot of growing amount of information on aging on it. So, um, you can just go to livebeyond.ai for that. Okay. Amazing. Well, we'll make sure to include that all in the show notes and when we get more info, especially anything on ovarian aging, I am really excited about that. Sure. Happy to happy to talk about that. We'll have a that paper will be coming out in the near future and uh um, I don't know if you've had us on yet, but you I really want to. If you can put in a good word for me, I would love that. Thank you so much for being here with me. Happy to do it anytime.