Speaker 1: Hi, this is Kopi Time podcast series on markets and
Speaker 1: economies from DBS Group Research. I'm Taiu Bei, chief economist,
Speaker 1: welcoming you to our 149th episode.
Speaker 1: Today we will discuss longevity with the foremost expert in
Speaker 1: the field. Brian Kennedy is distinguished professor of biochemistry and
Speaker 1: physiology at Yong Lu Lin School of Medicine at National
Speaker 1: University of Singapore. He's also the director of the Center
Speaker 1: for Healthy Longevity National University Health System. Professor Brian Kennedy,
Speaker 1: welcome to Kobe time.
Speaker 2: Thanks, pleasure to be
Speaker 2: here.
Speaker 1: It's great to have you. This is a subject close
Speaker 1: to my heart. I was just telling you right before
Speaker 1: this recording that all the 40-somethings and 50-somethings I know they're,
Speaker 1: they're deep into this. So I will have a lot
Speaker 1: of eager friends listening into this podcast. Uh prof, let's
Speaker 1: begin by defining senescence.
Speaker 2: Yeah, senescence is a, a term that gets used for
Speaker 2: multiple meanings, and I think that's one of the reasons
Speaker 2: that it's complicated for people to understand. So for instance,
Speaker 2: when a uh salmon comes back into the fresh water
Speaker 2: and dies, that's called senescence. Um, but I think most
Speaker 2: people
Speaker 2: In in today's discussion would refer to it as the
Speaker 2: uh cessation of division of cells in your body, uh, so, uh,
Speaker 2: cells can for a variety of different reasons, stop dividing
Speaker 2: and enter into a senescent state. Uh, and in that
Speaker 2: senescent state, they're no longer able to support regeneration of tissues,
Speaker 2: but they still are live cells and they can secrete
Speaker 2: factors that are pro-inflammatory.
Speaker 2: No
Speaker 2: Go ahead, please. No,
Speaker 1: go ahead, no, no, I'm, I'm listening. Yeah,
Speaker 2: so 11 thing senescence is therefore is to keep cells
Speaker 2: from becoming cancer cells. So when something goes wrong in
Speaker 2: a cell and it may be on its way to
Speaker 2: being a tumor cell, the senescence pathway can be invoked
Speaker 2: and that stops the cell from being able to divide.
Speaker 2: So in a sense, it's anti-cancer.
Speaker 2: On the other hand, these, these cells secrete pro-inflammatory factors
Speaker 2: that influence cells around them and maybe even throughout the
Speaker 2: body in some cases, if there's enough senescence and so
Speaker 2: that can actually stimulate aging and cancer, so it's kind
Speaker 2: of a trade-off.
Speaker 1: Right, OK, so that's exactly where I was to jump into.
Speaker 1: So the question I guess is, you know, so what
Speaker 1: are the molecular hallmarks of aging? Is it, is it
Speaker 1: the what you just described that the cells stop dividing
Speaker 1: and then they may be secreting inflammatory material?
Speaker 2: Yeah, I, I think we can list several different things
Speaker 2: that are driving the aging process. Cells in essence is
Speaker 2: certainly one of them. Um, the inability of your adult
Speaker 2: stem cells to replenish their tissues, levels of inflammation in
Speaker 2: the body, your telomeres, DNA damage, all of these things
Speaker 2: probably contribute to the aging process.
Speaker 2: Um, and, uh, it's still somewhat of a mystery to
Speaker 2: put them in order and talk about how they contribute,
Speaker 2: what percentage each of, each of them contributes. So I
Speaker 2: think a better way of thinking about it is that
Speaker 2: You have a a network in your body that maintains
Speaker 2: health and it's kind of a homeostatic network, uh, and
Speaker 2: this network can respond to things that happen in your body. You,
Speaker 2: you know, you get out in the sun, you get
Speaker 2: skin damage, you start eating a lot of fast food,
Speaker 2: you know, your body adapts to that and it keeps
Speaker 2: you healthy for the most part. But over time that
Speaker 2: network breaks down, and when it breaks down,
Speaker 2: These hallmarks of what you see, high levels of inflammation,
Speaker 2: your stem cells don't work as well, so all of
Speaker 2: a sudden the senescent burden goes way up. Um, and
Speaker 2: so they're, they're telling you that aging is happening, but
Speaker 2: I think preserving the network is really what we want
Speaker 2: to do to keep people young, not, you know, treat
Speaker 2: each hallmark separately. I think that that so far hasn't
Speaker 2: worked very well.
Speaker 1: And when does it begin? My son is 11 years old.
Speaker 1: Clearly he is not going through the process of aging yet,
Speaker 1: but would he at the age of 18, at 25,
Speaker 1: is it hard to put a marker around that?
Speaker 2: Well, I, I may even disagree with you. I think
Speaker 2: we we recently did a biomarker study using DNA methylation
Speaker 2: of 10,000 Singaporeans.
Speaker 2: And we happened to have a birth cohort in that study,
Speaker 2: so we were looking at newborn babies, and already we
Speaker 2: can detect that baby boys were older than baby girls. Uh,
Speaker 2: and so that suggests that maybe aging starts in the womb,
Speaker 2: you know, and that already there's something happening that's different
Speaker 2: between boys and girls.
Speaker 2: Um, so, certainly during development, you don't see manifestations of aging,
Speaker 2: you know, kids are getting stronger, they're getting smarter, their,
Speaker 2: their brain is, is developing, um, and so, you know,
Speaker 2: you begin to see the decline in aging in adulthood,
Speaker 2: you know, maybe.
Speaker 2: You know, starting around 30 maybe, but
Speaker 2: And there may be parameters that are driving that aging
Speaker 2: process that are not detectable, but happening throughout life.
Speaker 1: And is the manifestation of aging first in cognition or
Speaker 1: is it more physiological developments that you pick up as
Speaker 1: signs of aging?
Speaker 2: Well,
Speaker 2: I, I think that a lot of people would say
Speaker 2: that the ovarian aging is the first thing you really
Speaker 2: see in women, so you, you know, you have a
Speaker 2: decline in fertility starting in your 30s and
Speaker 2: Uh, menopause somewhere in your 40s and 50s, um, that's
Speaker 2: indicating that ovaries are, are aging, I think. Uh, also,
Speaker 2: your thymus tends to undergo what's called involution, which leads
Speaker 2: to a dramatic reduction in production of immune cells. So
Speaker 2: those are two things that happen relatively early during the
Speaker 2: aging process, um.
Speaker 2: Muscle loss, you know, starts usually around 40 and people
Speaker 2: say you, the average person loses about 1% muscle mass
Speaker 2: a year after that. Um, cognitive decline, and, and actually
Speaker 2: physical decline, it depends on how you measure it, you know,
Speaker 2: you don't see a whole lot of 40 year old
Speaker 2: athletes right at the top level.
Speaker 2: Um, and already when you're measuring how fast like neurons
Speaker 2: fire and connect, you know, it's already slowing down at
Speaker 2: that point, but it's hard to measure because your body's,
Speaker 2: like I said, is good at compensating, you know, so
Speaker 2: it finds other ways to adapt to to to things
Speaker 2: that are going a little bit slower and you don't
Speaker 2: really notice that in your daily life. So, if you
Speaker 2: really want to take really deep measures, you can already
Speaker 2: start to see things in 30s and 40s, but
Speaker 2: You know, in terms of actual functioning disease-free health, you know,
Speaker 2: that's usually not until 50s and 60s where you begin
Speaker 2: to see a significant decline.
Speaker 1: I recall reading somewhere that in terms of physics and
Speaker 1: pure mathematics, the pathbreaking discoveries come from scientists who are
Speaker 1: in their late 20s, early 30s. They even the Nobel
Speaker 1: laureates don't necessarily go through pathbreaking discoveries in the late
Speaker 1: 30s and 40s. I've heard about musicians that the really
Speaker 1: brilliant musicians are much younger than the older ones.
Speaker 2: Yeah, I think that that's certainly, it's certainly been well
Speaker 2: uh defined for math and physics. Um, you know, biology
Speaker 2: research is a little bit different because I have a
Speaker 2: whole team of people working with me and so it's not.
Speaker 2: You know, we may have a great discovery, I hope
Speaker 2: we do, but whether it comes from my brain or
Speaker 2: one of the young people's brains is debatable.
Speaker 1: Um, Proff Kennedy, I have heard you talk, ah, in,
Speaker 1: in public forum in, in terms of the distinction between
Speaker 1: lifespan and health span, and really that I've also heard
Speaker 1: you talk about this phrase, uh, compressed morbidity. So could
Speaker 1: you help us sort of walk through these three things?
Speaker 2: So, so healthspan is, it's a little bit hard to define,
Speaker 2: but I think you can understand that. It's the period
Speaker 2: of time that you're largely disease-free and that you're highly
Speaker 2: functional in life, um.
Speaker 2: And you typically that if the average lifespan in Singapore
Speaker 2: is 85, the average health span would be around low 70s. Um,
Speaker 2: and so there's a period of time, maybe a decade
Speaker 2: on average, where people are alive, but they're not in
Speaker 2: good health, or they're not functioning well, uh, and that
Speaker 2: would be, that's where all the healthcare costs are and
Speaker 2: that's where quality of life diminishes dramatically.
Speaker 2: So if you have an intervention that uh compresses morbidity,
Speaker 2: and we've published that with alphakitic glittering in mice, uh,
Speaker 2: what you see is that the health span goes up
Speaker 2: more than the lifespan. So it's, it causes a small
Speaker 2: increase in lifespan, but a big increase in health span.
Speaker 2: And so that period of time when you're sick and
Speaker 2: have multi morbidity gets diminished, and so that's what compressed
Speaker 2: morbidity is. And that's really what we would like to see, right?
Speaker 2: Are you, you.
Speaker 2: You know, jokingly, you'd like to be totally healthy and
Speaker 2: then eventually get hit by a bus. I mean, there's,
Speaker 2: I mean, maybe not, but you get the idea.
Speaker 1: Yeah, I think, uh, Atul Goanes being mortal in the
Speaker 1: very first chapter has something about like that his grandfather,
Speaker 1: who was a lawyer till his 90s, basically, you know,
Speaker 1: was healthy till the day he died because he got
Speaker 1: hit by something like that.
Speaker 1: Um, but, uh, I, you know, in WHO they have this, uh,
Speaker 1: life expectancy adjusted marker called HAL, HALE Health adjusted life expectancy.
Speaker 1: So is that the way to look at it then
Speaker 1: that instead of looking at
Speaker 2: that's one parameter you can use to try to measure
Speaker 2: health span. I think there are different ways to look
Speaker 2: at it, but, um, and like I said, it's there
Speaker 2: I don't know if there's consensus on how to measure it,
Speaker 2: but um.
Speaker 2: That would be one parameter you could think of, yes.
Speaker 1: I, I just like the fact that Singapore ranks number
Speaker 1: one in the health adjusted life expectancy metric.
Speaker 2: Yeah, I mean, Singapore is doing quite well, and you know,
Speaker 2: what I hope is that they really make a commitment
Speaker 2: to healthy longevity because the the time is right to
Speaker 2: do that and this island could be the, the model
Speaker 2: case for really extending health span because uh there's a
Speaker 2: lot of things going in advantage for Singapore, uh, it's small, manageable, um,
Speaker 2: already have good healthcare system.
Speaker 2: Uh, and I think there's also a population that believes
Speaker 2: in the government. So when the government takes the lead
Speaker 2: on something, people will follow, you know, you, you could
Speaker 2: say anything in the US you could say.
Speaker 2: You know, drink 3 cups of water a day or
Speaker 2: more and then half the population would disagree with you
Speaker 2: on my definitions
Speaker 1: for sure, absolutely, uh, I want to talk in greater
Speaker 1: detail about Singapore uh later. I just want to cover
Speaker 1: a couple of things first with you. Uh, when I
Speaker 1: told my wife that, you know, I was gonna
Speaker 1: Discuss with you this this health span lifespan issue. She
Speaker 1: basically said, well, it's largely genetics. So is it largely
Speaker 1: genetics or and she's a polysci PhD, so let's not
Speaker 1: necessarily give her full credence. You, the expert, tell me
Speaker 1: whether the genetics versus environment, how much do these things matter?
Speaker 2: How much trouble am I going to get if I
Speaker 2: disagree with her she has a very old you get.
Speaker 2: Um, there's certainly a genetic component, but most research suggests
Speaker 2: that it's relatively small, maybe 30% of the, of the equation,
Speaker 2: and the rest of it is sort of lifestyle environment,
Speaker 2: where you live, how you live.
Speaker 2: Um, and that it is very important. Now, there's an
Speaker 2: exception to that though. There are people that live to
Speaker 2: be centenarians. Um, they chose, they got there by choosing
Speaker 2: the right parents. Uh, that's very genetic when, so people
Speaker 2: with exceptional longevity have the right genetics, but this is
Speaker 2: extremely rare. The, the vast majority of us, um, uh,
Speaker 2: environment and lifestyle are probably more important.
Speaker 2: But this,
Speaker 1: this genetic lottery fascinates me. I'll give you my personal example.
Speaker 1: My mom, she's no longer with us. She had all
Speaker 1: sorts of morbidities, even at a fairly young age, diabetes
Speaker 1: related morbidity and so on in her 60s. My dad
Speaker 1: still around 90+. We had his 90th birthday last year.
Speaker 1: Fingers crossed, he lives longer, and he has never really
Speaker 1: stressed out about, you know, the right diet or the
Speaker 1: right pills, whereas my mom who did pass away, actually
Speaker 1: was far more worried about her
Speaker 2: health. Yeah.
Speaker 2: Well, there's two things I would say to that. One
Speaker 2: is that, uh, centenarians don't typically live well, that they
Speaker 2: have the genetics, right? So they, if you look at them,
Speaker 2: they were more likely to be a little bit overweight. Now,
Speaker 2: they weren't like crazy obese, but they were more likely
Speaker 2: to be a little bit overweight. Uh, and near Barzilai's
Speaker 2: study of Ashkenazi Jews, they're slightly more likely to be
Speaker 2: smoking than than the po you know, so they have
Speaker 2: the right genetics, they're resistant, um.
Speaker 2: I would also say that.
Speaker 2: I, I think it's great to be uh very alert
Speaker 2: to a healthy lifestyle and doing your best to live
Speaker 2: a healthy life, but I don't think worrying about it
Speaker 2: constantly is a good thing. And so, you know, I,
Speaker 2: I think that sometimes people forget the, the, the level
Speaker 2: that stress plays in their aging, uh, and trying to
Speaker 2: manage your stress, um, is, is critical. It's hard for
Speaker 2: us to study that in animals, but I'm convinced it's
Speaker 2: a critical component of aging, the mindset, you know.
Speaker 2: And so you said father, not worrying, and he seems
Speaker 2: to like go through life and take things kind of
Speaker 2: as they come, maybe yeah, your father's worried that could
Speaker 2: have been a factor.
Speaker 2: Right.
Speaker 1: Um, OK, so let's talk about the things that we
Speaker 1: can control, um, you know, diet, this issue has been
Speaker 1: around for maybe half a century, and there is my mother,
Speaker 1: so exactly. So since we can't control our father and mother, uh,
Speaker 1: the things that we can, let's talk a little bit
Speaker 1: about diet and exercise, the two things that, you know,
Speaker 1: a lot of people talk about, where do we stand
Speaker 1: in terms of scientific zeitgeist in these two areas?
Speaker 2: Let's
Speaker 2: start with exercise because I think it's a little bit
Speaker 2: of an easier discussion.
Speaker 2: Um, you do it. If some combination of resistance training
Speaker 2: and cardiovascular training is probably good for everybody. Um, it's
Speaker 2: important to try to do both, as as you get older,
Speaker 2: you wanna try to maintain that muscle mass. So one
Speaker 2: of the most important things you can do is keep
Speaker 2: your muscle mass. Um, but, you know, cardiovascular health is
Speaker 2: obviously good for your heart and your vascular system, and
Speaker 2: And a range of other systems as well. So, uh, the,
Speaker 2: the key to me is sustainability, you know, and trying
Speaker 2: to find exercise programs that fit your needs. If you're
Speaker 2: doing something and you don't like it, you're, you're gonna
Speaker 2: stop doing it. I just be honest, you know. So, um,
Speaker 2: for me, you know, I enjoy running. I, I kind
Speaker 2: of get my mindfulness from running.
Speaker 2: It's, it's meditative almost for me as well. Um, and
Speaker 2: so it's very good for me, and then I for
Speaker 2: I forced myself to go do weightlifting, and I've, I've
Speaker 2: learned to live with it. I don't love it, but
Speaker 2: I don't hate it either, and so, and I feel
Speaker 2: good after I, I complete it, so, uh, and I
Speaker 2: can see the benefit of doing it over the long term, so.
Speaker 2: You know, that that for me is what works, but if,
Speaker 2: if tennis works for you, that's great. The the key
Speaker 2: is find something that's sustainable.
Speaker 1: The um one point that I wanted, sorry, I, did
Speaker 1: I lose you? you can hear me, right? Yeah, um,
Speaker 1: we're going to get your diet for a second. I
Speaker 1: just want to share with you my personal slightly off-track
Speaker 1: observation on this issue. I also like to run. I
Speaker 1: also like the fact that during running all sorts
Speaker 1: A serendipitous thing can happen. I was in Dubai yesterday.
Speaker 1: I went running and I saw two peacocks flexing their
Speaker 1: plumes in just all glory. If I were driving or biking,
Speaker 1: I would not have seen that, and that that delight,
Speaker 1: I think will sustain my running habit for years to come. Yeah,
Speaker 2: I run outside instead of treadmills almost I only run
Speaker 2: on a treadmill if there's no other choice because I
Speaker 2: think you're right, you experience the world being outside running
Speaker 2: and
Speaker 2: Although I did try to run in Dubai last summer
Speaker 2: and that was, that didn't go well.
Speaker 1: December, January, February is what you want to do. Yeah, absolutely. Um,
Speaker 1: you had mentioned about the muscle loss aspect, about 1%
Speaker 1: muscle loss in your 40s onward, uh, so resistance training
Speaker 1: is something that you would want.
Speaker 1: People in their 40s onward to focus on as well,
Speaker 2: yeah, for sure. And also it's good for your bones,
Speaker 2: you know, one of the things that maintains bone density
Speaker 2: is putting resistance on your bones, you know, putting load
Speaker 2: on your bones. And so, um, when you're doing uh
Speaker 2: resistance training, you're not only helping your muscle but your
Speaker 2: bones as well.
Speaker 1: Shouldn't dairy also help with respect to bone? Got lots
Speaker 1: of calcium?
Speaker 2: Uh, dairy is complicated. Um, you want to maintain the
Speaker 2: appropriate calcium levels for sure, uh, as you age. Um,
Speaker 2: a lot of studies suggest that very high dairy, accelerates aging. Um,
Speaker 2: there are a lot of, uh, observational studies in, in
Speaker 2: humans to suggest that.
Speaker 2: Uh, so I tend to, I keep to a very
Speaker 2: low dairy diet. I eat yogurt and I, I will
Speaker 2: eat cheese sometimes, but I don't drink milk, uh, at all. So, but,
Speaker 2: you know, how your body reacts to that and what
Speaker 2: happens to your calcium levels is something you should be measuring,
Speaker 2: and this is, this is one point I would like
Speaker 2: to make is that people ask me about supplements and
Speaker 2: vitamins and all of all of these things.
Speaker 2: Well, you need to know where you are on this equation.
Speaker 2: You need to be able to, you need to know
Speaker 2: your vitamin levels. You need to know your meta metabolic levels, and,
Speaker 2: you know, we, and now we have a clinical aging
Speaker 2: clock where we can measure your biologic age based on
Speaker 2: 50 clinical variables that everybody should be getting anyway. You know,
Speaker 2: it's uh it's LDL and inflammatory factors and so if you're,
Speaker 2: if you're one of these people that likes to do interventions,
Speaker 2: whether it's lifestyle or supplements or drugs, a lot of
Speaker 2: people are taking rapamycin.
Speaker 2: You should be measuring outcomes as well and and trying
Speaker 2: to find the strategy that works best for you, uh,
Speaker 2: and I think a lot of people, uh, I think
Speaker 2: I always actually I think my my God, I don't
Speaker 2: know what your levels.
Speaker 2: These are.
Speaker 1: Um, prof, we sort of lost you in the last
Speaker 1: 30 seconds. Just let's just uh go back to that
Speaker 1: point of the, uh, after you talked about dairy, but
Speaker 1: the 30, 40 things that you can do to test
Speaker 1: your vitamin levels, that part, let's repeat that part.
Speaker 2: Yeah, so we recently generated a clinical chemistry clock that
Speaker 2: predicts your biologic age, and it does so from about
Speaker 2: 40 or 50 analytes that you commonly get when you get, uh,
Speaker 2: go to a doctor's office or hospital. And these are
Speaker 2: things you should be doing all the time, measuring these factors.
Speaker 2: These things like HbA1C, LDL, inflammatory factors.
Speaker 2: Um, and you should know what those are, and if
Speaker 2: you have them, we can also tell you your biologic age,
Speaker 2: but you should also know your vitamin levels. Typically these
Speaker 2: things are not measured, um, and people ask me, should
Speaker 2: I take vitamin D or B complex, and I, I'm like,
Speaker 2: I don't know, what are your levels? And they don't know. So, uh,
Speaker 2: you should measure yourself and, and pay attention to how
Speaker 2: you're doing, uh, before you just start taking a bunch
Speaker 2: of different things.
Speaker 1: All right, let's go to the broader issue of diet,
Speaker 1: which you already have sort of foreshadowed that it's a
Speaker 1: bit complex. um, what should one be eating and what
Speaker 1: should one be avoiding?
Speaker 2: Yeah, I mean, this is still highly debated. You can
Speaker 2: find experts that will say just about anything. I think
Speaker 2: the two common diets that people talk about for aging
Speaker 2: are a vegetable rich diet, uh, that's low in, uh,
Speaker 2: red meat and dairy, uh, kind of a Mediterranean diet, um, and, uh,
Speaker 2: and that's the one I tend to believe in, uh,
Speaker 2: and then there is another group that are very keto-oriented,
Speaker 2: so they're like high protein, high fat, no carbs, um.
Speaker 2: I think that that keto diet probably makes people lose weight,
Speaker 2: but it also unbalances your uh uh nutrition such that
Speaker 2: your body has to make relatively serious adaptation to what
Speaker 2: it needs, and I think over the long term, most
Speaker 2: of the evidence suggests that having high amino acid levels
Speaker 2: accelerates aspects of aging, uh, whereas if you look at
Speaker 2: the animal models where you keep
Speaker 2: Uh, calorie and take uh isochlorine, so you're, we're not
Speaker 2: changing total calories, and then you change macronutrients, it's actually
Speaker 2: high carb, low protein that's associated with longer lifespan.
Speaker 2: But there are two caveats to that. One is that
Speaker 2: it's complex carbs, not simple sugars. I think those are,
Speaker 2: are not good for you. Um, the other is that
Speaker 2: for humans, if you say you're eating a diet rich
Speaker 2: in carbohydrates, you're probably getting way too many calories. Carbohydrates
Speaker 2: is the fastest way to over nutrition, and I think
Speaker 2: that's why people perceive it as bad. But if you're
Speaker 2: eating complex carbs and you're not eating too many calories,
Speaker 2: it's probably not bad for you.
Speaker 1: But when I think of diet in this part of
Speaker 1: the world, there's a lot of noodles or rice in
Speaker 1: people's diet. Those are pretty simple carbs, right? Yeah,
Speaker 2: well, especially white rice. That's why there's been a lot
Speaker 2: of movement to have brown rice or other types of
Speaker 2: rice that are maintaining some of their nutrient richness.
Speaker 1: And I'm I'm, I'm I'm smiling a little bit because
Speaker 1: as you said, that these days you can hear just
Speaker 1: about every
Speaker 1: Variety of arguments in this regard, so in uh social
Speaker 1: media right now, there's a whole anti-brown rice movement about
Speaker 1: how brown rice is bad and we should be eating
Speaker 1: white rice, not really sure how scientific those observations are,
Speaker 1: but to your point there.
Speaker 2: I don't know the details of that argument, but like
Speaker 2: I said, I, I'm sure we could find somebody that
Speaker 2: advocates for the milkshake diet if we looked hard enough.
Speaker 2: This field is, is, um.
Speaker 2: Well, it's not, we have a rough idea of what
Speaker 2: people should do for health, but you know, there's a
Speaker 2: lot of details that we don't have good research on
Speaker 2: and
Speaker 2: A lot of serious scientists try to understand what's good
Speaker 2: for you and what's bad for you, and then on
Speaker 2: top of that, there's a lot of people trying to
Speaker 2: make money that are advocating for things that may not
Speaker 2: have a lot of science behind them. So, I, I,
Speaker 2: I get it. I understand when people are trying to
Speaker 2: do healthy longevity, it's not as easy as it sounds
Speaker 2: because depending on who you read and, and, and what
Speaker 2: nutrition religion you brought to you, you may be doing
Speaker 2: completely different things, so.
Speaker 1: So let's talk about the science of slowing or even
Speaker 1: reversing aging. You run a lab. You have talked in
Speaker 1: public forum a lot about alpha keto glutarates and also,
Speaker 1: if I'm pronouncing it right, spermmis. Tell us a little
Speaker 1: bit about these two molecules.
Speaker 2: Yeah, so, and, and I think that's just two of
Speaker 2: a bunch of different molecules. I'll start with AKG cause
Speaker 2: we've done a lot of research on it. Um, and,
Speaker 2: and actually we have a product on the market called
Speaker 2: Rejuin that has ato glutarate, it's time release version, plus
Speaker 2: some vitamins, uh, full disclosure, I'm involved with that company, um.
Speaker 2: But, uh, what, this is a central metabolite in the body.
Speaker 2: You may have heard of NAD, that's another central metabolite.
Speaker 2: These things are important for hundreds of reactions in the cell. Basically,
Speaker 2: they're important for metabolism and
Speaker 2: Excuse me, the levels go down with aging?
Speaker 2: Uh, and if you bring the levels back up, uh,
Speaker 2: you can improve aspects of health span or life span. Uh, so, uh,
Speaker 2: I think that there's pretty good evidence for both of
Speaker 2: those molecules. Uh, it's hard with NAD back up because
Speaker 2: you can't take pills with NAD, um, so that, so
Speaker 2: people do precursors, uh, with NM or you know things
Speaker 2: that are converted to NAD.
Speaker 2: But even NMR don't get good bioavailability, so you, you
Speaker 2: swallow a pill, very, not that much of it gets
Speaker 2: in the bloodstream. Um, there are ways around it. Now
Speaker 2: there's a company that I'm helping out called IX BioPharma
Speaker 2: that has a sublingual NAD, so this is directly NAD
Speaker 2: and it goes directly into the bloodstream that way. Uh, so, uh,
Speaker 2: those two, those two, metabolites are probably very important for aging.
Speaker 2: Uh, spermidine is a natural product, uh, and it activates
Speaker 2: autophagy in itself. Uh, and so autophagy is kind of a, a,
Speaker 2: a garbage collection service for your cells. It takes the
Speaker 2: damaged proteins and organelles and recycles the recycles them into, uh,
Speaker 2: primary ingredients that can make new proteins, uh, and it's
Speaker 2: important to clear out the damage in your cells and
Speaker 2: if you can enhance autophagy.
Speaker 2: It's typically good for aging as well, spermidine is one
Speaker 2: of the molecules that does that.
Speaker 2: But there are a lot of other natural products that
Speaker 2: I think are impacting aging, and we tend to uh
Speaker 2: believe that a lot of people believe that supplements are
Speaker 2: kind of all snake oil and uh again, it's a,
Speaker 2: it's a very, it's a profit-driven market, so, you know,
Speaker 2: it's kind of the wild west, but I think there
Speaker 2: are a lot of good ingredients in there that help people.
Speaker 2: The most important thing we need to do is figure
Speaker 2: out which people respond to which supplements or drugs or
Speaker 2: lifestyle changes, any of these things, and improve their aging,
Speaker 2: and right now we're still trying to figure that out.
Speaker 2: How do we personalize this? Um, you know, it's I,
Speaker 2: instead of telling everybody to take 10 different things or
Speaker 2: every everybody to take one thing, we, we really wanna
Speaker 2: know which person needs which intervention and, and that, I
Speaker 2: don't think we're there yet as a field.
Speaker 1: And your scientific approach is to try these things on
Speaker 1: mice and then try it on humans, or is there
Speaker 1: something in between?
Speaker 2: Well, we use a whole range of bottles, so we
Speaker 2: use uh uh yeast, worms, flies, killifish, which are these
Speaker 2: rapidly aging fish from Africa and, and mice. Uh, we
Speaker 2: don't use primates, uh, primates live a long time, so it,
Speaker 2: it kind of makes the studies hard and they also
Speaker 2: cost a fortune. Um, and so we, we don't do that.
Speaker 2: We do some stem cell models in the lab as
Speaker 2: well in in vitro organoid models, uh, but I think
Speaker 2: that
Speaker 2: My beliefs is that.
Speaker 2: There's gonna be a lot of conservation of, of aging
Speaker 2: pathways between animals and humans and other animals. Uh, the
Speaker 2: reason I say that is that, you know, we found
Speaker 2: the sirtuin pathway affects aging by studying single-celled yeast, and
Speaker 2: it turns out to be relevant to human aging. We
Speaker 2: found the MTOR pathway that way. The insulin IGF pathway
Speaker 2: comes from worms and flies.
Speaker 2: It seems like for whatever reason, the pathways that govern
Speaker 2: aging are highly conserved between species. And so I think
Speaker 2: if something is working in a mouse, there's a pretty
Speaker 2: high probability that it's gonna work in a human, and
Speaker 2: that's different from disease because the actual diseases humans get
Speaker 2: are different than the ones mice get. And so you
Speaker 2: can sort of engineer a human disease in a mouse,
Speaker 2: but that's not the same thing as having the disease
Speaker 2: developed naturally in a human.
Speaker 2: And so I think the disease models in mice are
Speaker 2: not as good as the aging model
Speaker 2: will be.
Speaker 1: OK, I'm absolutely fascinated by that point. I think David
Speaker 1: Sinclair in his book sort of talks about it that,
Speaker 1: you know, you don't have to wait for the final
Speaker 1: trial on humans. As long as you know these are
Speaker 1: not doing harm. If I show you some good results
Speaker 1: out of mice, you can probably go ahead and take it.
Speaker 1: I think that's David's argument to some extent.
Speaker 2: Yeah, I, I, in principle, I agree with that. I mean,
Speaker 2: you never for sure know about safety, so, you know,
Speaker 2: the question is, you know, where do you want to
Speaker 2: be on the, the, the risk reward spectrum for healthy longevity? Uh,
Speaker 2: if you want to be an early adopter, you know,
Speaker 2: and you know the safety profile and and the and
Speaker 2: and the potential efficacy of something.
Speaker 2: Uh, and you want to try it. I, I support that. I,
Speaker 2: I think one of the problems we have in medicine
Speaker 2: is that we don't have, we don't empower patients or clients, uh, and, um,
Speaker 2: they go in, they have 6 minutes with the doctor,
Speaker 2: the doctor looks at some charts and says you have
Speaker 2: to do this and you should do that and you
Speaker 2: should do that. And the patient's not invested in doing it.
Speaker 2: And so even when you give them statins, they tend
Speaker 2: not to take it, you know, so.
Speaker 2: Uh, compliance is very low. Uh, I think that we
Speaker 2: need to work on empowering people to make their own decisions,
Speaker 2: and if they wanna be like me, I try a
Speaker 2: lot of different things. If they wanna be, you know,
Speaker 2: on the edge and try things, I think it's OK
Speaker 2: as long as they're educated.
Speaker 1: OK to try metformin.
Speaker 2: Um, metformin is not my favorite intervention, but I, you know, it's,
Speaker 2: it's a very safe one. So there, there are very
Speaker 2: rare side effects that can happen. Uh, and so that,
Speaker 2: that should be kept in mind. Uh, I, I would,
Speaker 2: my personal recommendation on that is if you have, um,
Speaker 2: you should take metformin or, or one of the newer
Speaker 2: drugs in the market, a GOPonister.
Speaker 2: Uh, SCLLT inhibitors, but, um, it's still unclear whether those
Speaker 2: drugs for somebody with normal weight and normal glucose, whether
Speaker 2: those drugs are gonna enhance longevity. Uh, and there's evidence
Speaker 2: for the GLP agonist and also metformin that they take
Speaker 2: the wrong way, they can reduce muscle mass, which is
Speaker 2: not good. Now, my guess is that can be highly
Speaker 2: managed and anybody that
Speaker 2: is obese should be on one of these drugs cause the, the,
Speaker 2: the accelerated aging you get from obesity is extreme. Um,
Speaker 2: but I don't know what to recommend for people that
Speaker 2: are in relatively optimal, uh, weight at the moment. I
Speaker 2: think that's still an unknown.
Speaker 2: OK.
Speaker 1: Um, I was listening to one of your conversations recently
Speaker 1: where you were alluding to the next brave frontier, gene
Speaker 1: therapy and stem cell therapy.
Speaker 2: Yeah, I'm, I'm really excited about gene therapy because, you know,
Speaker 2: before we were identifying drugs that extend lifespan in different animals,
Speaker 2: we were doing a lot of genetic mutations. So, you know,
Speaker 2: we have hundreds of genes that affect aging in yeast
Speaker 2: and worms and maybe uh almost 100 in mice, I
Speaker 2: would guess. Uh, the what if you can effectively manipulate
Speaker 2: the genome, it gives you a much wider range of possibility.
Speaker 2: Uh, for changing aging, I believe, and it looks like
Speaker 2: gene therapy is finally, uh, reaching the, the, the forefront,
Speaker 2: you know, it's being used to treat rare childhood diseases, um,
Speaker 2: and there are already clinics that you can get gene
Speaker 2: therapy done in humans. It may be possible to do
Speaker 2: it in, in ways that you don't actually integrate the
Speaker 2: gene into the genome, and so you don't, you take
Speaker 2: less risk of making mutations in your genome with gene therapy.
Speaker 2: So I, I think it offers great promise. I'm not
Speaker 2: sure whether it's, it's, we're at the point where the, the,
Speaker 2: the rewards outweigh the risk for aging yet, but I
Speaker 2: think we'll get there and I think it'll open up
Speaker 2: a range of possibilities.
Speaker 1: I recently read Walter Isaacson's biography of Jennifer Doudna, the
Speaker 1: Code Breaker book, and the work is absolutely fascinating and
Speaker 1: the acceleration and innovation in that area in the last
Speaker 1: 1520 years is pretty astounding.
Speaker 2: Yeah, like CRISPR cusine is really a revolution, you know,
Speaker 2: and we, we could always make the genetic changes we
Speaker 2: wanted in yeast, and that's one of the reasons it
Speaker 2: was such a powerful organism, uh, but now you can
Speaker 2: effectively do that in cell culture and gene therapy is
Speaker 2: starting to be able to do it in people.
Speaker 2: Uh, it's, it's exciting for sure.
Speaker 1: Uh, how computationally intensive is some of this research, and
Speaker 1: the reason I asked you is because, you know, artificial
Speaker 1: intelligence and all the rage and, you know, large language
Speaker 1: models and so on. Um, are any of those recent
Speaker 1: developments in computer science helpful for the kind of research
Speaker 1: that we're talking about here? Yeah,
Speaker 2: it's dramatically changing the field. Half my labs doing AI
Speaker 2: and I never thought I would say that, um, and, um.
Speaker 2: You know, more and more people are coming to work
Speaker 2: every day on that topic, and it's, it's being used
Speaker 2: for a wide range of things. For one, we're using
Speaker 2: them to make biologic aging clocks to measure how you age, um,
Speaker 2: but we're also using it to select drugs that might
Speaker 2: be better at, uh, some disease or even extending longevity, um, we,
Speaker 2: we recently published a paper.
Speaker 2: Um, with careful and, uh, looking at how to query
Speaker 2: large language models to get, uh, appropriate answers for longevity.
Speaker 2: So like an example would be like, should I take
Speaker 2: rapamycin and 52 and, you know, I have diabetes, uh, and,
Speaker 2: you know, the people are doing this now, a lot
Speaker 2: of doctors will say you shouldn't ask large language models
Speaker 2: those questions, but people are asking them every day, it's happening.
Speaker 2: And so we're trying to figure out how to improve
Speaker 2: the responses of the LLMs.
Speaker 2: In a way that gives good medical advice to people.
Speaker 2: So I think that's just 3 examples. There's so many
Speaker 2: different ways that AI is being used now that it's, it,
Speaker 2: it's really quite amazing.
Speaker 1: Um, a few years ago I had Professor Dean Ho
Speaker 1: on my podcast. I'm sure you know Dean, and he
Speaker 1: was talking about in the context of personalized recommendation that
Speaker 1: AI can take in all the data from a patient
Speaker 1: overnight and then give you very specific recommendations of the
Speaker 1: dosage for the following day. At that time, I had,
Speaker 1: you know, of course, you know, it was years before
Speaker 1: large language models entered my consciousness, but I suppose this
Speaker 1: is one way of thinking about it as well.
Speaker 2: Yeah, it's getting there. I mean, you know, you can also.
Speaker 2: Take it down directions where you get the wrong answers,
Speaker 2: and so I think that the value of elements for
Speaker 2: medicine is, is, is gonna continue to, to grow, uh, and, uh,
Speaker 2: already I think you can get really meaningful information back,
Speaker 2: but with a note of caution perhaps.
Speaker 1: Right, I mean, for my personal work in the world
Speaker 1: of finance and economics, times I find it most useful
Speaker 1: is when I control the information that is ingesting. So
Speaker 1: when I upload a document and ask it to do
Speaker 1: some analysis on that, that's where the real value added
Speaker 1: comes to me. I don't necessarily trust it to tap
Speaker 1: the entire internet and give me the right answers.
Speaker 2: Yeah, yeah, but it's, it's changing so fast, you know,
Speaker 2: I'm starting to wonder when I'm gonna be obsolete.
Speaker 1: Um, uh, let's talk about Singapore. Uh, I know you're
Speaker 1: deeply involved in the research scene here. Give me a
Speaker 1: sense of how is the state of affairs on longevity
Speaker 1: related research in Singapore beyond your lab.
Speaker 2: Well, I, I think there's quite a, a field growing here. It's, it's, uh,
Speaker 2: not much was happening when it came 7.5 years ago.
Speaker 2: I mean, there was certainly, if you think of aging
Speaker 2: in a broader sense, there was good geriatric medicine here,
Speaker 2: there's geriatric research.
Speaker 2: You know, I jokingly say that geriatricians focus on aging.
Speaker 2: My job is to focus on non-aging. So, you know,
Speaker 2: we're typically looking at middle-aged people trying to prevent aging, uh,
Speaker 2: so it's a little bit of a different approach, but
Speaker 2: geriatrics is essential. You need geriatricians nowhere in the world
Speaker 2: has enough of them, and, uh, there's some very good
Speaker 2: ones here. And also there are programs focused on social
Speaker 2: aging that are very successful on.
Speaker 2: Um, uh, and, and other aspects of aging, financial aspects, and, and,
Speaker 2: and some health aspects of aging. Uh, we kind of
Speaker 2: brought this sort of molecular biology approach and to slow
Speaker 2: the aging process, and I, I think we're over the
Speaker 2: time we've built an ecosystem now of people that are
Speaker 2: thinking about this. I would also say that governments really, uh,
Speaker 2: even by the time we got here, they already knew
Speaker 2: how much of a problem they had with the aging population.
Speaker 2: I mean they have
Speaker 2: Um, major challenges because extremely low birth rate, people are
Speaker 2: living a long time, and immigration is a challenge on
Speaker 2: a small island like this. So, um, they'd already recognized
Speaker 2: this as a challenge. I think they've been taking their
Speaker 2: time trying to figure out where to invest in mitigating
Speaker 2: the problem, but, uh, I'm, I'm excited to hear that
Speaker 2: there's a lot of interest in focusing on healthy longevity
Speaker 2: going forward and
Speaker 2: You know, I, I think that it's really changing the
Speaker 2: mindset to say that, you know,
Speaker 2: Putting up better signs to keep people with Alzheimer's from
Speaker 2: getting lost is fine, uh, but it's not solving the
Speaker 2: economic challenge of aging. The way to solve that is
Speaker 2: to keep people healthy, keep them working, keep them raising
Speaker 2: their grandkids, keep them spending money in the economy and
Speaker 2: traveling and doing all the things that keep the economy moving,
Speaker 2: and the only way to get to there is by
Speaker 2: keeping them healthy, not waiting till they get sick and
Speaker 2: Throwing a lot of money and trying to treat them.
Speaker 2: So I think there's a recognition of that now and
Speaker 2: a belief that that's possible. So I think it's it's
Speaker 2: even gonna go faster as we go
Speaker 2: forward.
Speaker 1: And speaking of sort of the public sector of Singapore
Speaker 1: and its intervention in the day to day lives of Singaporeans,
Speaker 1: I mean, are you an advocate of, for example, subsidizing
Speaker 1: healthy diet or giving people exercise vouchers, or you think
Speaker 1: that there has to be a smarter ground up way
Speaker 1: of doing it as opposed to a top down manner
Speaker 1: from heaven from the government?
Speaker 2: Yeah, I don't think any government's figured this out yet, and, uh,
Speaker 2: you know, so this comes into play in a whole
Speaker 2: range of ideas. You can, you can do carrots like that.
Speaker 2: You know, you can also have an approach where you
Speaker 2: have to pay a little bit of your healthcare costs,
Speaker 2: where the government takes care of most of it, but
Speaker 2: you're on the hook for a little bit of it
Speaker 2: to try to motivate you to stay healthy, um.
Speaker 2: Different countries are trying different uh approaches right now, and
Speaker 2: in the first country that finds a strategy to really
Speaker 2: increase healthy lifestyle is gonna benefit tremendously. I guess the
Speaker 2: countries that are closest to that are probably Northern European countries, so.
Speaker 2: And Denmark, places like that, people are very active, they're
Speaker 2: less obese people and uh they're benefiting from a more
Speaker 2: healthy lifestyle. Uh, Singapore is not bad, but I think
Speaker 2: people don't exercise enough here, and it's partly climate. Uh, also, the,
Speaker 2: the food is relatively healthy, certainly it's healthy relative to America, but, uh,
Speaker 2: at the same time, you know, you go to the
Speaker 2: store and
Speaker 2: You know, you buy these cold teas in the store
Speaker 2: and they're like full of sugar. There's still some simple
Speaker 2: things that could be done that could really help out.
Speaker 2: And uh if I'm doing a 20k run, one of
Speaker 2: the piece full of sugar is really nice, but uh
Speaker 2: having it every day would be a disaster. I mean, we,
Speaker 2: we need to like
Speaker 2: Make simple changes, continue to make simple changes that promote
Speaker 2: the health of the population.
Speaker 1: Well, one thing I saw in Singapore 15 years ago
Speaker 1: when I moved here was the absence of covered sidewalks,
Speaker 1: and today it's a sea change. There's so many sidewalks
Speaker 1: that are covered and it makes a huge difference in
Speaker 1: my ability to run through those areas.
Speaker 2: Yeah, me too. Uh, I, I agree with that. Uh,
Speaker 2: little things like that help for sure, but they're not
Speaker 2: the solution, you know, the solution is also to just
Speaker 2: go after the molecular biology and slow aging.
Speaker 2: Um, I, I think we need to, those sort of
Speaker 2: environmental changes are good, but they don't, they stand alone.
Speaker 2: I don't think they're going to solve the problem.
Speaker 1: Sure, I have saved the hardest question for you at
Speaker 1: the end, which is, is aging a disease and if
Speaker 1: it's a disease, should it be covered by health insurance,
Speaker 1: any aging related treatment?
Speaker 2: I'll I'll turn the question around and say that it
Speaker 2: should be covered by health insurance, whether it's a disease
Speaker 2: or not.
Speaker 2: You know, we can get into semantic arguments about whether
Speaker 2: it's a disease, but if it's, if you don't wanna
Speaker 2: call it a disease, you have to at least acknowledge
Speaker 2: it's the biggest risk factor for every disease we're afraid of. Um,
Speaker 2: and when you think of the most successful drugs on
Speaker 2: the market, they're not treating overt diseases. They're treating high
Speaker 2: blood pressure. Why do you treat high blood pressure? Cause
Speaker 2: you don't want a heart attack. You, you don't want
Speaker 2: cardiovascular disease in the future. They're treating high glucose, uh,
Speaker 2: they're treating high cholesterol.
Speaker 2: Um, these are the drugs that work. They're, and they're reimbursed.
Speaker 2: And so if we acknowledge these things are risk factors
Speaker 2: for disease and we should treat them, we should also
Speaker 2: acknowledge that aging is a 100 times bigger risk factor
Speaker 2: than any of those. So we should reimburse treatment for
Speaker 2: that too. I, I honestly, I think I would call
Speaker 2: it a disease, but I, as long as I can
Speaker 2: treat it and it gets reimbursed, you can call it
Speaker 2: anything you want.
Speaker 1: Uh, well, that's, that's a great note too, and uh
Speaker 1: Professor Brian Kennedy, thank you so much for your time
Speaker 1: and insights.
Speaker 2: Anytime. Thanks
Speaker 1: a lot. A pleasure. Thank you to our listeners as well. Uh,
Speaker 1: Kobe Time was produced by Ken Delbridge at Spy Studios.
Speaker 1: Violet Lee and Daisy Sharma provided additional assistance. It is
Speaker 1: for information only and does not represent any trade recommendations
Speaker 1: or drug recommendation.
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