Speaker 1: They say that only two things in life are certain,
Speaker 1: death and taxes. For the lucky among us will pass
Speaker 1: away quietly at an old age. But why is aging
Speaker 1: and thus death inevitable? And how do we even define aging? Yes,
Speaker 1: you can define it by the ticking of the clock,
Speaker 1: but is there a biological way to define it that
Speaker 1: gives you a better shot at really understanding how the
Speaker 1: passage of time has worn away at your body. If
Speaker 1: two people in their thirties can mix their old cells
Speaker 1: together to make a brand new baby, then why can't
Speaker 1: those same two people just start making young cells for themselves?
Speaker 1: And shouldn't evolution favor living a really long time so
Speaker 1: we can make more babies and be around to help
Speaker 1: them grow. Aging can be a counterintuitive phenomenon, and Daniel
Speaker 1: and I get many questions from our audience the extraordinaries
Speaker 1: about the aging process. However, despite the furrows in my
Speaker 1: forehead that get deeper each year and that my son
Speaker 1: sometimes stares at, this biologist is not an expert in
Speaker 1: the science of aging. But lucky for us, we were
Speaker 1: able to get doctor Venki Ramakrishnan, author of Why We Die,
Speaker 1: The New Science of Aging and The Quests for immortality
Speaker 1: to come onto the show to answer your questions. Welcome
Speaker 1: to Daniel and Kelly's extraordinarily Old Universe.
Speaker 2: Hi.
Speaker 3: I'm Daniel. I'm a particle physicist. I round my age
Speaker 3: up two hundred.
Speaker 1: Hello. I'm Kelly Waidersmith. I study parasites and space And Daniel,
Speaker 1: last time we talked, you rounded up to fifty. Have
Speaker 1: you just decided that, now that you're fifty, yere rounding
Speaker 1: up to one hundred because that is not a helpful
Speaker 1: wait around.
Speaker 3: I think that's totally consistent. When I was forty eight,
Speaker 3: I called myself fifty, and now that I'm fifty, I
Speaker 3: got a round up to one hundred. It totally makes sense,
Speaker 3: not to me. Plus, I think I look pretty good
Speaker 3: for one hundred.
Speaker 1: Yeah, you look great for one hundred, But I say
Speaker 1: you look good for fifty two.
Speaker 4: But like, I don't.
Speaker 1: Yeah, I know that that kind of rounding doesn't make
Speaker 1: sense to me. But that's all right, all right.
Speaker 3: So here's my question for you today, Kelly. If you
Speaker 3: could take a pill that would extend your life to
Speaker 3: a thousand years or a million years, would you do
Speaker 3: you want to live a super crazy long life?
Speaker 1: Umm? Al right, So one, okay, So selfishly, I would
Speaker 1: need to know about the quality of that life, and
Speaker 1: if the quality of my life was going to be
Speaker 1: as good it is now, for all of that time,
Speaker 1: I would think about it. But to be honest, the
Speaker 1: only reason I'm thinking that I might want to say
Speaker 1: yes is that I want to live at least as
Speaker 1: long as my son lives, because he's going to need
Speaker 1: care his whole life, and I don't want him to
Speaker 1: ever be alone. And so if I could live as
Speaker 1: long as he lives, one hundred percent, So what about.
Speaker 3: You, No, I see, life is like a hike. You know,
Speaker 3: hikes are wonderful. There's oneful moments you're glad you went
Speaker 3: on them. You're also glad when they're over. Nobody wants
Speaker 3: to be in a hike that lasts until the end
Speaker 3: of the universe. And maybe sometimes the best part of
Speaker 3: a hike is when you get to sit down at
Speaker 3: the end, you're like, oh wow, what a nice walk done.
Speaker 1: Especially at the end of a good hike, Yeah, you're like, ah,
Speaker 1: all right, I'm ready to be done.
Speaker 3: Exact.
Speaker 1: And my grandpa passed away recently, and I think he
Speaker 1: had that kind of life. He hiked it was a
Speaker 1: good trip, and at the end he told everyone, he's like,
Speaker 1: I'm ready, and then he passed away into sleep, and
Speaker 1: I was like, man, I really hope that's in the
Speaker 1: genes somewhere, because that's pretty solid.
Speaker 3: And I hope that listening to this podcast has improved
Speaker 3: that everybody's quality of life out there were making your
Speaker 3: hike through life more pleasant.
Speaker 1: Maybe it will improve their quality of sleep, which at
Speaker 1: the end of the episode will discover is an important
Speaker 1: part of being healthy. So we're doing our part.
Speaker 3: You're saying that listening to the podcast could technically scientifically
Speaker 3: extend your lifespan.
Speaker 1: Maybe maybe listen to our prior episodes about how you
Speaker 1: evaluate scientific statements and see what you think, dear listeners,
Speaker 1: and whether.
Speaker 3: You should believe people who have skin in the game exactly.
Speaker 1: Yes, all right, Well, so we get loads and loads
Speaker 1: of questions about aging from the extraordinaries, and so I
Speaker 1: pulled them all together. We found an amazing expert to
Speaker 1: answer the question. Amazing, amazing, he does such a great job.
Speaker 3: How do you know this Nobel Prize?
Speaker 1: Kelly Oh, thanks for pitching myte We both were on
Speaker 1: the short list for the Royal Society Book Prize. Yep,
Speaker 1: Why We Die is thank you Rama Christnan's book, and
Speaker 1: A City on Mars was my book, and we both
Speaker 1: made the short list for the Royal Society Prize.
Speaker 3: And you're just gonna omit those crucial piece of information
Speaker 3: that you won the prize. So Kelly is the author
Speaker 3: of a book which edged out a Nobel Prize winning
Speaker 3: nonfiction science book.
Speaker 1: I was not gonna mention that. Thank you for ult
Speaker 1: over the years.
Speaker 3: I appreciate it, all right, Well, this is a wonderful
Speaker 3: conversation with a deep expert who also has the unusual
Speaker 3: quality of being able to explain things clearly yes.
Speaker 1: And being so nice, so nice.
Speaker 5: Yeah.
Speaker 1: Anyway, So I had so much fun. I feel so
Speaker 1: lucky we got to do.
Speaker 3: This interview before we bring on our expert, who want
Speaker 3: to know abel prize in this area. We asked you
Speaker 3: guys what you thought was the reason for aging. Here's
Speaker 3: what people had to say.
Speaker 2: I underested it to be oxidative pressures where new copies
Speaker 2: of things just aren't quite as good as they used
Speaker 2: to be and there are errors throughout. Short answer telemeres
Speaker 2: real answer, so that there's someone to say I wouldn't
Speaker 2: do that if I were you to the younger generations,
Speaker 2: it's not like the clouds are going to yell at themselves.
Speaker 6: Certain proteins that mark ourselves or do something along the
Speaker 6: lines of maintaining how are unique gets repeated or transcripted deggregate.
Speaker 3: Over time, the.
Speaker 6: Body forgets how to make a new body the way
Speaker 6: that it once did.
Speaker 5: We age as a consequence of too many gas station burritos,
Speaker 5: ninety nine cent big gulps and betrayal by Teilomeir.
Speaker 7: At a molecular point of view, it's really hard to
Speaker 7: maintain consistency in the gazillion times molecules and the cells
Speaker 7: needs to produce these error skips that canap until the
Speaker 7: whole body the case, my.
Speaker 2: Short answer is we age due to the passage of time.
Speaker 8: I think we age because we need to die ultimately.
Speaker 8: I think it's conducive, if not crucial, to the evolution
Speaker 8: of life itself, for organisms to have a finite lifespan.
Speaker 2: Every beginning as an end.
Speaker 9: So I believe I've read somewhere that the reason why
Speaker 9: we age is because there is a shortening of some
Speaker 9: kind of a protein or molecule within our cells.
Speaker 2: And so for DNA current to fray and just gets
Speaker 2: left up to entropy.
Speaker 8: Aging and death are just part of the evolutionary.
Speaker 7: Process and processes that have brought us to where we
Speaker 7: are today.
Speaker 2: It's just a fact.
Speaker 3: Thanks everybody for your speculation on this concept. Now let's
Speaker 3: talk to the expert and find out what we know
Speaker 3: and what we don't know.
Speaker 1: Doctor. Thank you. Rama Krishnan was initially interested in physics,
Speaker 1: but I'm going to go ahead and give a point
Speaker 1: to biology because he transitioned to focusing more on this
Speaker 1: field and the biology stuff worked out well for him
Speaker 1: because in two thousand and nine he received a Nobel
Speaker 1: Prize for his work on ribosomes. He was President of
Speaker 1: the Royal Society from twenty fifteen to twenty twenty and
Speaker 1: recently wrote the book Why We Die, The New Science
Speaker 1: of Aging and the Quest for Immortality. And today we'll
Speaker 1: be talking about the science of aging. Welcome to the show.
Speaker 2: Thank you, and thank you for having me.
Speaker 1: Yeah, we're super excited to have you. We get so
Speaker 1: many questions from our audience about aging, and every time
Speaker 1: I'm like, look, I know when you look at me,
Speaker 1: I look like the right person to ask about.
Speaker 3: Well, they should look at me then, and there's so
Speaker 3: much discussion out there about aging and how to prevent
Speaker 3: it and if it's possible, and so much snake oil
Speaker 3: being sold out there. It's so important to cut to
Speaker 3: the chase.
Speaker 2: It's certainly having a moment, and I'm a little bit cynical.
Speaker 2: I think it has to do with my generation, the
Speaker 2: boomer generation, that's used to having everything it wanted in life,
Speaker 2: suddenly coming to terms with getting old, and so, you know,
Speaker 2: there's a lot of anxiety in the air. Although having
Speaker 2: said that, you know, this fear of death and fear
Speaker 2: of aging is simply as old as humans, you know,
Speaker 2: because ever since we learned about mortality, we've fretted and
Speaker 2: worried about it. And I like to say we may
Speaker 2: be the only species that's aware of mortality. Other animal
Speaker 2: maybe are aware of death, but they're not aware that
Speaker 2: they all have a finite lifespan and everybody is going
Speaker 2: to die. I'm not sure that other species have that
Speaker 2: understanding that we do. And when we somehow obtain that understanding,
Speaker 2: perhaps as a result of cognitive development, language and so on,
Speaker 2: ever since then, it has become it became a theme
Speaker 2: and if you look at most religions. They're all about,
Speaker 2: you know, how to deal with death and what happens
Speaker 2: after we die.
Speaker 1: I don't know if it's a blessing or a curse
Speaker 1: that our species is aware of that.
Speaker 2: Yeah, I mean many species aren't even aware of death,
Speaker 2: you know, it just simply happens.
Speaker 3: Well, can I start us off with a very broad
Speaker 3: sort of philosophical question, which is, how do you define
Speaker 3: aging biologically? Because as a physicist, I might think, well,
Speaker 3: you have a clock and it starts and it stops,
Speaker 3: and that's your age. But we're interested in more than that, right,
Speaker 3: It's some sort of like decrease in the quality of life.
Speaker 3: You're gradually moving towards death. It's this fact that you
Speaker 3: don't just like live for sixty two years and then poof,
Speaker 3: you're done. Your body degrades. How do we define aging
Speaker 3: in a crisp way scientifically?
Speaker 2: Yeah, so it's not. It's definitely related to the chronological
Speaker 2: clock to time, but the rate is very different, not
Speaker 2: only for species, it's vastly different for species, but it's
Speaker 2: also different for individuals within a species. If you go
Speaker 2: to your high school reunion, you will immediately be aware
Speaker 2: of that the fact that people don't age at the
Speaker 2: same rate, and I think aging molecular biologists would define
Speaker 2: it as the gradual accumulation of changes and damage to
Speaker 2: us over time that can happen different rates in different individuals.
Speaker 2: And it's not just damage. Some of it has changes
Speaker 2: that occur with time. It may occur at different rates
Speaker 2: in different individuals, and these changes may have a purpose
Speaker 2: early in life, for example, modifications of our DNA, but
Speaker 2: they cause us or at least they're strongly correlated with
Speaker 2: aging later in life. So that's how I define it.
Speaker 2: And this accumulation of changes in damage leads to a
Speaker 2: gradual loss of function, and when that loss of function
Speaker 2: reaches some point where some critical system fails, then you
Speaker 2: have death. And so a death is a result of aging,
Speaker 2: but its exact moment can't be predicted because in a
Speaker 2: complex system, you can't predict exactly when a critical component
Speaker 2: will fail.
Speaker 3: Aging and changes, but that must mean very different things
Speaker 3: to different parts of your body. You're talking about your
Speaker 3: nerves or your skin or your eyes. Are there ways
Speaker 3: we have to measure it?
Speaker 2: It happens at every level. It happens at every level.
Speaker 2: But I would say fundamentally it happens at the molecular level,
Speaker 2: and that then manifests itself and each increasing level of complexity.
Speaker 2: So you can go from molecules to collection of molecules
Speaker 2: in our cell, to components of the cell, to cells themselves,
Speaker 2: and then entire tissues, and you know the way cells
Speaker 2: communicate with each other, like our immune system. So you
Speaker 2: can see that, you know, it happens at the molecular level,
Speaker 2: but it starts manifesting itself at increasingly higher levels, you know,
Speaker 2: until the point that you know, we see aging as
Speaker 2: various forms of frailty, you know. So in fact, a
Speaker 2: very good measure of aging is actually something called the
Speaker 2: frailty index. They'll measure things like can you get out
Speaker 2: of bed? How fast can you walk you know, fifty yards?
Speaker 2: What's your grip strength? How good is your eyesight? How
Speaker 2: good is your cognition? You know, how good is your memory?
Speaker 2: So all of those things are indications of frailty at
Speaker 2: a macroscopic level, at a level that you and I experience.
Speaker 2: But ultimately the underlying causes are molecular.
Speaker 1: Okay, and is aging universal. So we're getting to one
Speaker 1: of our first listener questions right now. One of our
Speaker 1: listeners noted that they had heard stories about immortal organisms
Speaker 1: and they wanted to know are they actually immortal.
Speaker 2: Yeah, I had to say, there's a lot of hype.
Speaker 2: What happens is people will study an organism that ages
Speaker 2: very slowly, and suddenly they'll say, oh, this has no
Speaker 2: sign of biological mortality. Let me back up and explain
Speaker 2: what I mean by that. So, in normal species, the
Speaker 2: likelihood of that we are going to die at any
Speaker 2: given time keeps increasing exponentially. So for example, that chances
Speaker 2: that you'll die when you're ten are very small, but
Speaker 2: the chances you'll die in the next year when say
Speaker 2: you're ninety five or one hundred or almost fifty percent, okay,
Speaker 2: so the chances keep going up. Now, in some organisms,
Speaker 2: it appears that that likelihood of dying you know, of
Speaker 2: aging events, not of being eaten by a predator or
Speaker 2: starving or anything else. Those are called external causes. But
Speaker 2: you know aging, just dying of aging, that probability doesn't
Speaker 2: seem to go up with time. And so there are
Speaker 2: some species, like a freshwater species called the hydra. There's
Speaker 2: another species called the immortal jellyfish, and these tend not
Speaker 2: to show any signs of biological aging. That is, the
Speaker 2: likelihood it's going to die just doesn't seem to change
Speaker 2: with time. But in fact what is happening is it's
Speaker 2: probably aging very very slowly. So if you looked, if
Speaker 2: you simply followed a hydra in the wild, it'll die
Speaker 2: of some other cause, not of old age. But if
Speaker 2: you kept it safe and followed it long enough, you
Speaker 2: will find that it too, gradually ages because no regeneration
Speaker 2: is perfect. You know, the reason hydra and jellyfish appear
Speaker 2: not to age is they constantly regenerate their tissue using
Speaker 2: specialized cells called stem cells. In a way, they're like plants.
Speaker 2: You know, plants have stem cells all over themselves, and
Speaker 2: that's why you can take a cutting from a plant
Speaker 2: and you know, grow an entirely new tree with it. Right,
Speaker 2: we can't do that, but you know, some animals regenerate,
Speaker 2: like starfish. You know, it cut off an arm and
Speaker 2: it'll regenerate an arm. And you know, some of these
Speaker 2: species can regenerate, you know, any tissue, and but it's
Speaker 2: not perfect. And so I would say to your listener
Speaker 2: that yes, everything will die, but they die at different rates.
Speaker 2: I mean, they age at different rates.
Speaker 3: And so everything ages. It's universal across organisms. Do we
Speaker 3: understand why we age? Like, is it an inevitability of
Speaker 3: like thermodynamics or molecular copying or something, or is it
Speaker 3: an evolutionary advantage?
Speaker 2: Well, there there are two ways of looking at it.
Speaker 2: One is, you know, the physicist way would be that
Speaker 2: you know, second law wins and there's always increase in
Speaker 2: entropy and disorder and eventually things sort of degrade. And
Speaker 2: you know, life is not a you know, equilibrium system.
Speaker 2: The problem with that is that life is not a
Speaker 2: closed system, and if you apply enough energy and enough
Speaker 2: resources you can reverse damage. And in fact that's what
Speaker 2: we do. So why is it then that we age
Speaker 2: and die? Well, I'll tell you the evolutionary argument. The
Speaker 2: evolutionary argument is resources are limited and throughout our history
Speaker 2: and in fact, until recently, resources were limited for humans
Speaker 2: as well. You know, we had to struggle to have
Speaker 2: enough food to live and so on. When resources are limiting,
Speaker 2: the organism has a choice to make. Does it put
Speaker 2: more of the resources into maintenance and repair, which requires energy,
Speaker 2: requires food, et cetera. Or should those resources be put
Speaker 2: in too rapid growth and development? Now, if you take
Speaker 2: a mouse. For example, a mouse lives about two years,
Speaker 2: whereas a blue whale lives a few hundred years. So
Speaker 2: why is it that there's this vast difference. Well, the
Speaker 2: evolutionary argument is that evolution doesn't actually care how long
Speaker 2: you live. Evolution simply cares about how successful are you
Speaker 2: going to be at passing on your genes because it's
Speaker 2: selecting for those genes, it's not really selecting for you
Speaker 2: as an individual. And so in the case of a mouse,
Speaker 2: there's no point in spending a lot of resources getting
Speaker 2: a mouse to live to be forty years. And the
Speaker 2: reason is that long before that it'll be eaten, or
Speaker 2: it'll die of starvation or in a drought, or all
Speaker 2: of a zillion external causes. And so in the case
Speaker 2: of a mouse, it's more advantageous from an evolutionary point
Speaker 2: of view for a mouse to grow very rapidly, produce
Speaker 2: lots of offspring, and then you know, it doesn't matter
Speaker 2: whether it dies, Whereas with larger animals, their metabolism is
Speaker 2: also slower, so they take longer to mature, their offspring
Speaker 2: take longer to produce and grow up and mature, and
Speaker 2: so in there it does make sense for evolution to
Speaker 2: have selected for longer lifespan in order to ensure fitness. Okay,
Speaker 2: because otherwise it may men not actually have the chance
Speaker 2: to reproduce, or not to reproduce enough. And it gets
Speaker 2: worse than that. It's not even that evolution doesn't care
Speaker 2: what happens to you after you've produced your offspring. Evolution
Speaker 2: also will select for traits that are advantageous early in
Speaker 2: life that will get you to maturity and reproduction, even
Speaker 2: if those exact same traits will cause you to age
Speaker 2: later in life. And there are many examples of that
Speaker 2: in my book. For example, certain mechanisms that cause us
Speaker 2: to age may have evolved as anti cancer mechanisms. Now,
Speaker 2: of course you want to prevent cancer early in life,
Speaker 2: but later in life they may cause aging, and ironically,
Speaker 2: cancer itself increases as we age the likelihood of getting cancer.
Speaker 2: But that's a different story.
Speaker 3: Can you give us an example of an anti cancer
Speaker 3: strategy that causes aging?
Speaker 2: Leader Yeah, sure so. One very classic example is that
Speaker 2: most of the cells in our body can only divide
Speaker 2: a certain number of times, and then they reach a
Speaker 2: state called sinesence. Senessen cells are these dysfunctional cells that
Speaker 2: can't divide and they actually secrete inflammatory compounds. And as
Speaker 2: we age, we accumulate more sinescent cells and that becomes
Speaker 2: a problem and inflammation becomes a problem. Now, why do
Speaker 2: cell stop dividing? Well, it turns out that our chromosomes
Speaker 2: are linear DNA molecules and their ends are specialized struck.
Speaker 2: It is called telomeres. Now, the copying mechanism for DNA,
Speaker 2: every time it cell divides, that DNA has to be copied.
Speaker 2: The copying mechanism is such that our chromosomes get slightly
Speaker 2: shorter every time the cell divides. Okay, and these ends
Speaker 2: have a special structure. Now, when they become too short,
Speaker 2: that structure unravels. When it unravels, the end of our
Speaker 2: chromosomes looks to the cell like a broken piece of DNA.
Speaker 2: That the cell has evolved mechanisms that if there's a
Speaker 2: DNA break, it will either try to repair it, or
Speaker 2: if it can't repair it, it will send the cell
Speaker 2: into Sinessence. Why, because a cell with a defective genome
Speaker 2: is at cancer risk because it's about you know, it
Speaker 2: could do all kinds of you know, abnormal things, and
Speaker 2: it's much better to send that cell off to sinessence
Speaker 2: and have it be removed by the immune system, then
Speaker 2: have it continue with a DNA defect or a chromosome defect. Right,
Speaker 2: So the cell has evolved as DNA response damage response
Speaker 2: in order to get rid of cells that are problematic
Speaker 2: in this way. But of course that same thing is
Speaker 2: causing senessens and increase in senescent cells as we get
Speaker 2: older and causing us to age. So that's a very
Speaker 2: you know, clear example of how something that may have
Speaker 2: evolved as an anti cancer mechanism early in life really
Speaker 2: is a cause of aging later in life.
Speaker 3: All Right, I want to hear a lot more about that,
Speaker 3: but first we have to take a break. Okay, we're
Speaker 3: back and we're talking about aging.
Speaker 1: So you mentioned that as cells go on and replicate
Speaker 1: the telomeres, you get shorter. But we and this is
Speaker 1: another listener question, but we're able to, you know, combine
Speaker 1: our gam meets with somebody else and make a fetus
Speaker 1: that has all new cells. And you also mentioned that starfish,
Speaker 1: can you regenerate an entire arm using stem cells? So
Speaker 1: why is it inevitable that our cells will break down
Speaker 1: when we seem able to set the clock back if
Speaker 1: we want to so we.
Speaker 2: Have evolved so that most of our cells have lost
Speaker 2: that ability to regenerate, probably because you don't want all
Speaker 2: of the trillions of cells in our body to be
Speaker 2: able to keep dividing at will, because that is also
Speaker 2: a cancer risk, okay, because they could acquire mutation and
Speaker 2: then they could become cancerous. So we have specialized cells
Speaker 2: called stem cells, which can keep regenerating. They don't go
Speaker 2: into senescence, and these specialized cells their role is to
Speaker 2: regenerate tissue. Now where do these stem cells come from, Well,
Speaker 2: they came from the fertilized egg. The fertilized egg is
Speaker 2: the ultimate stem cell because it's what is called a
Speaker 2: toty potent stem cell. That means it can make everything
Speaker 2: in the body, including the placenta. Okay, then that separates
Speaker 2: off into placental cells and the cells that actually form
Speaker 2: the fetus and the body, you know, and the organism.
Speaker 2: Early in development, those cells are called pluripotent because they
Speaker 2: can make any kind of tissue. They could make kidneys,
Speaker 2: they can make lungs, they could make brain cells, they
Speaker 2: can make anything. But as the fetus, as the embryo
Speaker 2: I should say, develops, the stem cells become more and
Speaker 2: more specialized. And then you have amatopoetic stem cells, which
Speaker 2: can make anything in the blood system, and that includes
Speaker 2: all of our immune system and our red blood cells,
Speaker 2: et cetera. Another kind can make anything in the nervous system,
Speaker 2: you know, neurons, glia, all of those cells. Others can
Speaker 2: make skin and hair and so on. So you get
Speaker 2: the picture. The stem cells are becoming more specialized, but
Speaker 2: those stem cells have a balancing act. They have to
Speaker 2: reproduce so that they maintain the stem cell population, but
Speaker 2: they also have to differentiate and produces more of the tissue.
Speaker 2: So there's always this switch going on. Do they reproduce
Speaker 2: more of themselves so you have more stem cells, or
Speaker 2: do they make the tissue keep regenerating the tissue they are,
Speaker 2: and there's always this balance. But as we get older,
Speaker 2: our stem cells get depleted because they also get defective.
Speaker 2: They also age, they also become sinescent, and so you
Speaker 2: get this depletion of stem cells. You also get the
Speaker 2: remaining stem cells are not optimal. They become what are
Speaker 2: called clones. Instead of having a diverse population of stem
Speaker 2: cells as when we're young, you get these clonal stem
Speaker 2: cells which are suboptimal. They're selected for being able to
Speaker 2: reproduce rather than being effective at generating tissue. So these
Speaker 2: stem cells also decline. So that's why we can't keep
Speaker 2: going forever, you know, by regenerating tissue. Now, the other
Speaker 2: question your listener had was, you know what about our
Speaker 2: germ cells. You know we can you know, we keep
Speaker 2: producing babies that are age zero. They're not. You know,
Speaker 2: in my book, I point out that a forty year
Speaker 2: old woman doesn't give birth to a baby that's twenty
Speaker 2: years older than a twenty year old woman. They're both
Speaker 2: zero right, born at a time zero. So that's a
Speaker 2: combination of two things. One is our germline cells are
Speaker 2: highly protected against damage. They have better repair mechanisms for
Speaker 2: repairing DNA damage. They're shielded against DNA damage, et cetera.
Speaker 2: So that's one aspect. The others there's a brutal selection process.
Speaker 2: You know, a female is born, a female human is
Speaker 2: born with about a million or so eggs. But you know,
Speaker 2: if you look at the number of menstrual cycles and
Speaker 2: a woman over a lifetime, it's only maybe a few hundred.
Speaker 2: So why do you need a million eggs? You know,
Speaker 2: when you're really only going to use at the most
Speaker 2: a few hundred, right, So that's because there's a lot
Speaker 2: of selection in the process of going from the germline's
Speaker 2: precursor cells to the egg that's actually eventually selected for ovulation.
Speaker 2: There's a lot of selection. Sperm, of course, you know,
Speaker 2: is highly selected. I mean, you know, each fertilization event
Speaker 2: there you know, I don't know how many I would
Speaker 2: had to guess and take a guess, but maybe it's
Speaker 2: a million sperm cells or something, and out of that
Speaker 2: is only one is selected, you know, So they have
Speaker 2: to raise and they have to you know, win the competition.
Speaker 2: So they are also selected for fitness for health. And
Speaker 2: then after the fertilized egg is formed, you know, it
Speaker 2: is also checked. So if the developing embryo is at
Speaker 2: all defective, there'll be spontaneous abortion. Often a woman won't
Speaker 2: even know it, you know, the very early spontaneous abortion.
Speaker 2: Later abortions are what we call miscarriages, and that's another selection.
Speaker 2: And even within the growing embryo, cells are selected against
Speaker 2: if they're defective. The embryo keeps growing, but it kills
Speaker 2: off cells that are defector, which I found remarkable. So
Speaker 2: it's this combination of selection and protection that ensures that,
Speaker 2: you know, the child that is born is has its
Speaker 2: aging clock soon reset, okay, at each generation.
Speaker 3: But is it technically possible for us to reset our
Speaker 3: own clock? Is it just like a bad idea evolutionarily,
Speaker 3: or is there something that prevents us from just like
Speaker 3: constantly being at teko zero.
Speaker 2: I don't see how you would reset your entire clock.
Speaker 2: You know, in the whole organism there are people. So
Speaker 2: if I were to back up just a little bit,
Speaker 2: there is an example of taking a fully grown adult
Speaker 2: cell and making a whole new animal from it, Okay,
Speaker 2: And the first time that was done was by John
Speaker 2: Gordon who received the Nobel Prize for it when he
Speaker 2: cloned a frog from a skin cell. So he took
Speaker 2: a skin cell from an adult frog and implanted the
Speaker 2: nucleus of that cell into the egg of another frog
Speaker 2: and then just grew it up and it resembled the
Speaker 2: frog from which the skin cell had been taken, you know,
Speaker 2: so it was essentially a clone. And then people asked
Speaker 2: could they do it to mammals? And that made big
Speaker 2: headlines when Dolly the Sheep was cloned. Now Dolly the
Speaker 2: Sheep turned out to be very sickly sheep and died
Speaker 2: at about half the age of a normal sheep. So
Speaker 2: everybody said, ah, this is because Dolly the Sheep was
Speaker 2: cloned from a fully grown adult cell which was already
Speaker 2: kind of old and damaged and didn't go you know,
Speaker 2: wasn't a normally produced sheep. It was done by this
Speaker 2: weird cloning procedure. But it turns out that there are
Speaker 2: many other cloned animals, and in fact, with Dolly, the
Speaker 2: other cohorts like Daisy and Debbie, they're all females that
Speaker 2: had d names and these sheep though by and large,
Speaker 2: had normal lifespans. And so that means that you could actually,
Speaker 2: you know, reset the clock to substantial degree by erasing
Speaker 2: all the marks on the DNA. Okay, it's not perfect,
Speaker 2: because the cloning itself involved lots of selection. You know,
Speaker 2: it is very very inefficient. It only works small fraction
Speaker 2: of the time, and most of them end up in
Speaker 2: miscarriages or or they don't take and so on. So
Speaker 2: at least in theory it's possible. Now, could we do
Speaker 2: to cells in a more systematic way what Dolly the
Speaker 2: sheep or John Gerdon did with his frog, Because they
Speaker 2: just treated it in various ways, but they didn't have
Speaker 2: a clear idea of what was what was it? What
Speaker 2: were they doing to make that adult cell go back
Speaker 2: to resembling a fertilized egg and start growing a new animal.
Speaker 2: You know, it's like going backwards in time, right, And
Speaker 2: so a Japanese scientist named Shinya Yamanaka asked, could you
Speaker 2: take these stem cells that are in the final stage,
Speaker 2: or even the final cells like a skin cell or
Speaker 2: you know, lung cell or whatever, and have them go
Speaker 2: all the way back to pluripotent stem cells so that
Speaker 2: they could then, you know, become any kind of cell.
Speaker 2: And remarkably, he found that if you take four genes
Speaker 2: and introduce them into one of these adult cells and
Speaker 2: turn them on, you could change the genetic program of
Speaker 2: the cell and have it go backwards all the way
Speaker 2: back to pluripotence. Now, this has created a big industry
Speaker 2: in the stem cells because stem cells are going to
Speaker 2: be useful for all kinds of things. For example, if
Speaker 2: you want to replace damaged tissue, you know, let's say
Speaker 2: you want to replace pancreas in diabetics so that they
Speaker 2: can produce insulin. There are all kinds of things being
Speaker 2: talked about, and they're you know, cartilage and a guy
Speaker 2: like me with very bad joints. So or for a
Speaker 2: guy like me with you know, very little hair, you
Speaker 2: could imagine stem cells stimulating new hair growth, Okay, and
Speaker 2: that would be a billion dollar industry.
Speaker 3: Yeah, if you could develop some like gun you pointed
Speaker 3: a part of your body and you're like, make this younger.
Speaker 2: Exactly, So people asked, now, the problem with going all
Speaker 2: the way back is that you have the risk of cancer,
Speaker 2: you know, because it's you're taking these cells. They're not
Speaker 2: quite exactly the same as a normal embryonic development is
Speaker 2: it's the somewhat artificial process that you're using to go
Speaker 2: backwards in development. And when they try to grow those
Speaker 2: plur iportent stem cells, they often would get these tumor
Speaker 2: like growths called teratomas, and so there is definitely a
Speaker 2: cancer risk. But what a number of scientists asked was
Speaker 2: supposing you turn on these Yamanaka factors transiently, you know,
Speaker 2: just turn them on and then figure out a way
Speaker 2: to turn them off after a while, then what would happen. Well, astonishingly,
Speaker 2: they tried this in mice and they found that the mice,
Speaker 2: you know, resembled younger animals. They suddenly had better fur
Speaker 2: and muscles, and you know, by various markers they seemed younger.
Speaker 2: So this idea of cellular reprogramming is a big area
Speaker 2: in the longevity field, but it's still in early stages.
Speaker 2: Even though there's a lot of excitement the idea that
Speaker 2: tomorrow you're going to go and get a treatment that
Speaker 2: will suddenly make all yourselves younger, it's really not going
Speaker 2: to happen anytime soon, and it's because there are lots
Speaker 2: of problems. One is, you know, you have to get
Speaker 2: the right dose, you have to make or it's safe.
Speaker 2: You have to make sure it goes to the tissues
Speaker 2: and just the right amounts. These are all big challenging problems.
Speaker 2: And you know, of course a long term cancer risk
Speaker 2: is another problem. So I think it's very exciting and promising,
Speaker 2: but it's not something that's around the corner as it's
Speaker 2: often hyped. I mean that's my opinion. Of course, you know,
Speaker 2: people will disagree with me those but remember a lot
Speaker 2: of these people have quite a lot of skin in
Speaker 2: the game. They have financial interests, they've founded companies and
Speaker 2: so on. So you have to slightly take what they
Speaker 2: say with a pinch of salt.
Speaker 1: So you've mentioned that one of the reasons that we
Speaker 1: age and die is because it has something to do
Speaker 1: with resources.
Speaker 2: And with evolutionary choice. Basically. Yeah.
Speaker 1: So now many humans like me live in an environment
Speaker 1: where there are too many resources maybe, and we should
Speaker 1: take in fewer resources, and we live in an environment
Speaker 1: where we're better and better at being able to treat cancer,
Speaker 1: because it seems like we keep coming up across you know,
Speaker 1: cancer is the thing that's holding us back. So if
Speaker 1: we were in a high resource environment and we could
Speaker 1: figure out how to cure cancer, do you think we
Speaker 1: might be able to get our life spans up one
Speaker 1: hundred years or something.
Speaker 2: Well, somebody did a calculation. Demographer named Jay Olshansky from Chicago,
Speaker 2: who's a leading expert in this area, did a calculation
Speaker 2: a number of years ago, maybe twenty five thirty years ago,
Speaker 2: which suggested that if there are four major causes of
Speaker 2: major diseases of old age that caused death, one you
Speaker 2: mentioned cancer, the other one is diabetes, a third one
Speaker 2: is heart disease, and the fourth one is dementia. Neuer
Speaker 2: degenerative diseases and of course the newer degenerative diseases are
Speaker 2: among the hardest to treat. But let's say you could
Speaker 2: eliminate all four of them. The suggestion is you're only
Speaker 2: gain about fifteen years of lifespan if you eliminated all
Speaker 2: of these four causes. And the reason is that they
Speaker 2: will not affect the normal process of aging, you know,
Speaker 2: which leads to frailty of you know, system wide frailty.
Speaker 2: And there's always this argument, is aging a disease And
Speaker 2: people say, well, you know, all of these major things
Speaker 2: like diabetes, cancer, etc. The risk goes up with age.
Speaker 2: In fact, the biggest risk factor is age. The older
Speaker 2: you are, the more likely you are to get one
Speaker 2: of these things, or more or several of them. But
Speaker 2: the other argument is that, well, these diseases don't happen
Speaker 2: to everybody. Not everybody dies of cancer, not everybody has
Speaker 2: heart disease, and also young people get cancer, so it's
Speaker 2: not directly related. And aging, on the other hand, is
Speaker 2: something that happens to every single person and it's inevitable.
Speaker 2: So how can you call something that's both ubiquitous and
Speaker 2: inevitable a disease. It's simply a process of life. And
Speaker 2: I tend to agree with that. But the reason they
Speaker 2: want to call it a disease is because then it's
Speaker 2: easier to get approval for clinical trials. Well, I think
Speaker 2: they ought to try some other thing. For example, they
Speaker 2: can choose a target, a disease target that's strongly correlated
Speaker 2: with aging, for example ostere arthritis or loss of various
Speaker 2: functions and so on, and then they could use that
Speaker 2: as the measure of success of their drug. So there
Speaker 2: are ways to get around it. But I don't think
Speaker 2: that just eliminating these diseases will increase lifespend that much.
Speaker 2: And in fact, even people who in the aging field
Speaker 2: who have bet so. Olshansky was on one side of
Speaker 2: a bet with another gerontal just named Stephen Ostad. Stephen
Speaker 2: Ostad made a bet with him that the person who
Speaker 2: lives to be one hundred and fifty has already been born, okay,
Speaker 2: And that bet was made some time ago, and they
Speaker 2: bet it so that in one hundred and fifty years,
Speaker 2: you know, the amount would be worth that a billion
Speaker 2: dollars or something. Of course, you know, maybe it'll cost
Speaker 2: a billion dollars to buy a sandwich, but by that time.
Speaker 2: But anyway, but they made this bet. Now. Stephen Ostad
Speaker 2: also doesn't believe that it's just going to be because
Speaker 2: of eliminating disease. Rather, what he thinks is that we're
Speaker 2: making progress in slowing down or arresting aging itself, and
Speaker 2: that's the reason why we may end up living longer.
Speaker 2: And for example, you know, there's a drug called wrappamicin
Speaker 2: which is somewhat is related to caloric restriction, which also
Speaker 2: allows animals to live longer. That, for example, can increase
Speaker 2: lifespan in mice by you know, twenty or thirty percent. Well,
Speaker 2: if we live you know, ninety years, you know, thirty
Speaker 2: percent of that would already get us to one hundred
Speaker 2: and twenty or so. You see, So maybe he's counting
Speaker 2: on on things like that. I tend to be on
Speaker 2: the Olshansky side. I think that I'm really fundamentally increasing lifespan,
Speaker 2: and especially healthy lifespan. Is not going to be as
Speaker 2: easy as they say, because it's highly multi factorial. There's
Speaker 2: so many things going on.
Speaker 3: Well, how do we know you're not just a shell
Speaker 3: for big death?
Speaker 2: You know?
Speaker 3: Are you being paid by the death industry?
Speaker 1: All right, well, take a break, and when we get
Speaker 1: back we'll talk.
Speaker 4: More about aging, and we're back.
Speaker 1: So we have another question from a listener, and here
Speaker 1: it is, I'm curious why immune systems seem to decline
Speaker 1: with age. Shouldn't they get supercharged because by then, when
Speaker 1: you're old, you've basically seen everything.
Speaker 2: It is true that immune systems are exposed to more
Speaker 2: things as we age, but immune systems are essentially a
Speaker 2: collection of cells, and the cells themselves age, and so
Speaker 2: they don't respond as well as they do when we're
Speaker 2: younger or when we're in our prime. And this has
Speaker 2: to do with molecular damage affecting higher levels like the
Speaker 2: cell and communication between cells, and so for all kinds
Speaker 2: of reasons, our immune system as a result of this
Speaker 2: accumulated damage doesn't function optimally.
Speaker 3: So it's got a lot more wisdom, but like less
Speaker 3: energy and effectivity.
Speaker 2: Yeah, and actually it doesn't function as well. For example,
Speaker 2: it responds in an aberrant way. It's not as well regulated.
Speaker 2: You know, the immune system always has to be very
Speaker 2: finely regulated because you don't want to react against yourself
Speaker 2: or against harmless things. You only want to react against
Speaker 2: truly dangerous entities. So that fine balance is disrupted, and
Speaker 2: so you get essentially a dysfunctional immune system, and you
Speaker 2: also get a lot of inflammation as a result. So,
Speaker 2: for example, I mentioned those sinescence cells. The reason those
Speaker 2: sinessn cells secrete inflammatory compounds is as a signal to
Speaker 2: the immune system that hey, there's something wrong here, come
Speaker 2: and clear it up. And so the immune system will
Speaker 2: come there. It may be the side of a wound,
Speaker 2: or an infection or or some other stress, and it
Speaker 2: will deal with it. But as we get older, not
Speaker 2: only do the number of sines and cells increase, but
Speaker 2: the immune system doesn't respond as well to the signals,
Speaker 2: and so you get this sort of auto catalytic or
Speaker 2: you know, you get this essentially, this explosion in the
Speaker 2: growth of sines and cells and inflammation.
Speaker 3: And is this something that's understood across species. One of
Speaker 3: the listeners asked why cats and dogs have the same
Speaker 3: age related diseases that we do, but they appear at
Speaker 3: a younger age, maybe smaller number of years.
Speaker 2: That's simply the fact that this allocation of repair to
Speaker 2: maintenance and repair to growth and reproduction, that balance is
Speaker 2: different for different species. You know, you could ask why
Speaker 2: do whales live so long? Well, one reason is they
Speaker 2: have a slower metabolism than say animal like a mouse.
Speaker 2: But the other reason also is but they have a
Speaker 2: large number of repair enzymes. You know, if you look
Speaker 2: at just DNA repair enzymes, they have many different repair
Speaker 2: enzymes when they sequence the genome of some of these species,
Speaker 2: and elephants, for example, have many more copies of a
Speaker 2: DNA repair enzyme than mice.
Speaker 3: Do because they live longer, so they need more repairs.
Speaker 2: Yeah, and they have to they have to maintain that. Also,
Speaker 2: there is a paradox They have many more cells, and
Speaker 2: so the chance that one of their cells could become
Speaker 2: cancerous and kill the whole animal is much higher in
Speaker 2: a larger animal than in a small animal. But paradoxically
Speaker 2: it's mice get cancer more often than elephants, and that's
Speaker 2: because the elephants do have this additional capacity to repair.
Speaker 2: So it's all evolution really just optimizing for fitness. Remember,
Speaker 2: evolution does not optimize for long life. It doesn't care
Speaker 2: about long life. It cares about survival of genes because
Speaker 2: that's what it selects for.
Speaker 1: This might be a little too far off topic, but
Speaker 1: I've seen articles that say, like green sharks never get cancer.
Speaker 1: Are there actually species that never get cancer or it
Speaker 1: just takes them away and we don't see it often.
Speaker 2: It is almost entirely that we don't observe them long enough.
Speaker 2: So for example, I'll give you an example of Glapicus tortoises, right,
Speaker 2: you know, they live to be two hundred years old.
Speaker 2: And I like to joke that there's probably a Galapicus
Speaker 2: tortoise wandering around now that might have actually met Darwin.
Speaker 2: Oh you know, that's a cool thought, right, But anyway.
Speaker 3: Let's have them on the podcast so exactly, so.
Speaker 2: You know, if they could talk, they might be able
Speaker 2: to tell you quite a bit. But anyway, No, it
Speaker 2: was thought for a while that these things, these tortoises
Speaker 2: don't age. Well, actually they do age. If you look
Speaker 2: at old tortoises, they have terrible eyesight, and you know,
Speaker 2: there's slow moving, there's skins, you know, old you know
Speaker 2: they have all these.
Speaker 3: They don't know how to use the VC exactly.
Speaker 2: They have all of the same problems, and it's just
Speaker 2: that it happens more slowly, Okay.
Speaker 1: And I gotta say, Daniel, I think the VCR joke
Speaker 1: aged you more than anything.
Speaker 3: Well, the fact that you laughed at it aged you.
Speaker 1: Oh, you got me. That's true. That's true. So let's
Speaker 1: jump back, if that's okay, to another example of folks
Speaker 1: trying to extend lifespan. So I've heard of examples of
Speaker 1: like taking blood from young mice and giving it to
Speaker 1: old mice, and then I think there's a guy, Brian
Speaker 1: Johnson who's trying to limit aging by using his son's blood.
Speaker 1: Is there any evidence that that's anything other than nuts.
Speaker 2: That's an excellent question. And it is true that when
Speaker 2: they connected an old rat to a young rat, the
Speaker 2: old rat benefited by the exchange of blood and the
Speaker 2: young rat actually suffered. And then they were wondering whether
Speaker 2: it was really due to the blood itself, or maybe
Speaker 2: the young rat had better liver and kidneys to detoxify
Speaker 2: the blood, and so it wasn't just the blood, but
Speaker 2: it was just that it had better organs to clean
Speaker 2: up blood. So they separated them and simply give them transfusions,
Speaker 2: and they found that, in fact, the effect was still there,
Speaker 2: but it was more that the old rat had things
Speaker 2: in it that were harmful to the young rat. That
Speaker 2: was more the case than that the young blood was
Speaker 2: beneficial to the old rat. But it did. But there
Speaker 2: was some effect both ways. Now this is true, and
Speaker 2: when the people discovered it, they caught all sorts of
Speaker 2: creepy phone calls from rich people asking, you know, whether
Speaker 2: they could get young blood and so on, and in fact, companies.
Speaker 3: Where do babies? It's kind of exactly.
Speaker 2: And in fact companies sprouted up, and as you can imagine,
Speaker 2: mostly in California. I think.
Speaker 3: That's what I would get, you mean, the center of
Speaker 3: innovation and forward thinking and creativity.
Speaker 5: That's why you said, ye, anyway, that's somehow obsessed with youth.
Speaker 5: But but anyway, some of these companies would would get
Speaker 5: blood from young donors and sell them at a huge
Speaker 5: markup to rich people wanted them. And in one case,
Speaker 5: the FDA actually tried to shut one a company down
Speaker 5: and then it opened up under a different name. And
Speaker 5: in one case the CEO said, well, look, our people
Speaker 5: simply don't have the time to wait for clinical trials,
Speaker 5: you know, Oh my goodness. It was really bizarre coming from,
Speaker 5: you know, a CEO of you know, a health based company.
Speaker 3: But you're saying that there are real benefits to having
Speaker 3: transfusions of blood from young people.
Speaker 2: Well, there's certainly seemed to be in animals, and so
Speaker 2: there's a big bar of research to find out what
Speaker 2: is changing in blood as we get older, and what
Speaker 2: do these factors do. You know, if they're harmful in
Speaker 2: old age, what do they do? Maybe we can inhibit them,
Speaker 2: or if they're beneficial in early life, maybe we can
Speaker 2: take advantage of that and introduce them into older people.
Speaker 2: So I think that's a very legitimate and broad area
Speaker 2: of research and lots of very you know, top scientists
Speaker 2: from very well known universities are actually working on that.
Speaker 2: But you know, this idea that you should just take transfusions,
Speaker 2: you know, it's not really going to help that much
Speaker 2: at this point. And Brian Johnson whom you mentioned, actually
Speaker 2: did this experiment of keeping it all in the family.
Speaker 2: He took blood from his son and gave his blood
Speaker 2: to his dad. But he's also, I mean to give
Speaker 2: him some credit, he's obsessed with a you know, or
Speaker 2: not aging to be more precise. He spends like a
Speaker 2: couple of million dollars a year on all kinds of
Speaker 2: longevity treatments and measurements, and you know probably has you know,
Speaker 2: fitness programs and all sorts of things.
Speaker 3: Okay, Well, the thing that fascinates me about Brian Johnson
Speaker 3: is that he does take a lot of data, right,
Speaker 3: he is.
Speaker 2: Exactly focused data on metrics, right, He's focused on metrics.
Speaker 3: But he doesn't look young, Like even though he says
Speaker 3: he has all these metrics which are equivalent to an
Speaker 3: eighteen year old, he still looks like a vampire. So
Speaker 3: he sort of captures this like, well.
Speaker 2: I would say, no, I'll give him credit. He's his
Speaker 2: late forties. He looks pretty good for late forties. But
Speaker 2: I'll tell you my son is in his late forties.
Speaker 2: Yeah he does none of this stuff. Yeah, okay, but
Speaker 2: he runs regularly and eats well, and he looks just
Speaker 2: as good as Brian Johnson. And I'm not just being biased.
Speaker 2: You could look him up on online. He's a cellist.
Speaker 3: So well, you're definitely biased, but I don't don't not
Speaker 3: believe you, But you know, I think it raises a
Speaker 3: deeper question, which is, like, is it possible to be
Speaker 3: young biologically by all of these metrics, as you say,
Speaker 3: you know, you're measuring the damage to whatever molecular mechanisms,
Speaker 3: but still somehow not be young in the sort of
Speaker 3: social sense.
Speaker 2: That's that's a very good question. You know. So you
Speaker 2: know I mentioned the high school reunion and how we
Speaker 2: all look different. Yeah, so that's led to this quest
Speaker 2: for biological markers of age. Okay, yeah, because you want
Speaker 2: to know. You know, your birthday may have been, you know,
Speaker 2: forty years ago, but how old are you really in
Speaker 2: biological terms? Right, So the people have come up with
Speaker 2: different clocks, you know. So one clock is this so
Speaker 2: called DNA methylation clock. So these are little tags that
Speaker 2: get attached to our DNA from the time we're conceived. Okay,
Speaker 2: it happens even in utero. We're aging even in utero, okay,
Speaker 2: And that's apparently better correlated with with mortality than chronological age.
Speaker 2: You know, So chances that you're going to die are
Speaker 2: more correlated with your data infilation than they are with
Speaker 2: your date of birth. So so that's you know, used
Speaker 2: as a clock.
Speaker 3: But does that suggest that if you could somehow adjust
Speaker 3: that you would extend your life? I mean, is it
Speaker 3: causal or is it correlated?
Speaker 2: That's the real question. You know, we don't know the
Speaker 2: extent of causality. The other case is that as we age,
Speaker 2: extra sugar groups get added to our proteins. It's called lication.
Speaker 2: And so you can measure this, you know, addition of
Speaker 2: sugar groups to our proteins, and when that happens to
Speaker 2: our proteins of our immune system, it also doesn't work
Speaker 2: as well. So people think that it has some connection
Speaker 2: with this, you know, decay of the immune system. But anyway,
Speaker 2: that's another clock. Now people will sell you kits. They'll
Speaker 2: tell your denim infylation kit or a glacation kit or
Speaker 2: a full blood you know library. You know, they'll just
Speaker 2: analyze a bunch of stuff in your blood to give
Speaker 2: you a sort of biological age, and each one will
Speaker 2: say this is our thing, is the most accurate? Okay. Now,
Speaker 2: I think these are all very useful research tools because
Speaker 2: if you have a longevity intervention, like an anti aging intervention,
Speaker 2: you can see are these markers changing more slowly or
Speaker 2: are they changing at the same rate? Okay, and they'll
Speaker 2: give you a good idea of you know, are you
Speaker 2: aging faster or not. But people need to come together
Speaker 2: and agree on a panel. You know, I don't think
Speaker 2: a single clock is going to tell you the whole story. Yeah, okay,
Speaker 2: I think they need to agree on a panel and
Speaker 2: then say okay, here's a panel and this is what
Speaker 2: it represents, and it might be a complex thing. There's
Speaker 2: no point in talking about your biological age because your
Speaker 2: liver may not be the same age as your kidney
Speaker 2: or your lung. You know, you can imagine if you're
Speaker 2: an alcoholic, your liver might be older than other parts
Speaker 2: of your bodies. So I think people need to have
Speaker 2: a more complex view of aging, of biological age.
Speaker 3: But don't we also need to unravel this question of causality.
Speaker 3: I mean, if you identify a marker, even or even
Speaker 3: a complex panel that indicates biological age, adjusting those results
Speaker 3: doesn't necessarily make you younger. It's like I can turn
Speaker 3: back the clock literally and it will read a different number.
Speaker 3: Doesn't make me younger. And if this is just a comment,
Speaker 3: one more thing which is one of my favorite mechanisms
Speaker 3: that Brian Johnson keeps track of is that, and I
Speaker 3: love that he's totally transparent about his data, is that
Speaker 3: he measures his erection quality during the night and he
Speaker 3: posts this data online, which I think is hilarious. But
Speaker 3: you know, just as an easy example, if the guy
Speaker 3: took a viagara every night when he went to you
Speaker 3: probably would have like glorious erections all night long. It
Speaker 3: wouldn't make him any younger, right.
Speaker 2: That's true. But you know, let's take dinner methylation. You know,
Speaker 2: so one of the things about those reprogrammed cells is
Speaker 2: that they have changed the methylation pattern as well, you know.
Speaker 2: So I mean that one of the distinct things about
Speaker 2: going back to an early embryonic state is that the
Speaker 2: methylation pattern is different. So there may be some element
Speaker 2: of causality, because methylation does change the program of our
Speaker 2: gene expression. So if you're going back to an earlier state,
Speaker 2: you maybe you're going back to an earlier program. But
Speaker 2: I agree that, you know, causality, you know, needs to
Speaker 2: be established by careful experiments. You know, is is it
Speaker 2: sufficient to reverse methylation and without cause on automatic cause
Speaker 2: something to look younger. There are some scientists who claim
Speaker 2: that they have reversed aging just by this process, but
Speaker 2: it's highly controversial.
Speaker 1: So I imagine our listener is going to want to know,
Speaker 1: as an expert in aging who doesn't believe, you know,
Speaker 1: that there's a magic pill out there that's going to
Speaker 1: give us an extra fifty to one hundred years, what
Speaker 1: do you do to slow the aging process?
Speaker 2: Yeah, yeah, I should say, you know, there's no theoretical
Speaker 2: reason why we couldn't all start living to be one
Speaker 2: hundred and fifty eventually. Okay. The thing that I'm what
Speaker 2: I'm saying is that we don't know how to do
Speaker 2: that at this point, and more importantly, we don't know
Speaker 2: how long it's going to take. And that's where I
Speaker 2: differ with some of the more extreme optimists that the
Speaker 2: field is full off. Okay, but what we can do
Speaker 2: right now before then? I want to address one question.
Speaker 2: If you ask most aging research, they would say, oh,
Speaker 2: we're not interested in extending lifespan. We're really interested in
Speaker 2: extending health span. Okay. And this whole thing is based
Speaker 2: on an idea called compression of morbidity. So as we
Speaker 2: get older, we start accumulating various morbidities. You know, you
Speaker 2: could say diabetes is one, or heart disease or dementia, accounts,
Speaker 2: et cetera. You know, frailty of various kinds or morbidities,
Speaker 2: and the ideal life would be that you're extremely healthy
Speaker 2: and then suddenly we have undergo a rapid decline. Okay.
Speaker 2: This is called compression of that morbidity into a very
Speaker 2: short space of time. You have a span of time.
Speaker 2: So that's the goal. The question is is that even possible. Well,
Speaker 2: in the last few decades we are all living healthier
Speaker 2: as a result of improvements in health, but it's also
Speaker 2: extended our lives, so that our period of morbidity has
Speaker 2: not changed. Okay, so it's just postponed. And in fact,
Speaker 2: you know, we're living more years and it's sort of
Speaker 2: decline than you know veras before, we might have died
Speaker 2: brutally quickly, okay, as soon as something went wrong, you know,
Speaker 2: would collapse and die, and now we're sort of prolonging
Speaker 2: it and have a long period of morbidity. So it's
Speaker 2: not clear that as we improve things, we're going to
Speaker 2: somehow keep healthy and reach some fixed limit and then collapse.
Speaker 2: It may simply be that we'll live a bit longer
Speaker 2: and still have that inevitable period of decline. That's an
Speaker 2: unsolved question, no matter what people will actually say. The
Speaker 2: one exception to this are super centenarians. These are people
Speaker 2: who live to be over one hundred and ten and
Speaker 2: even over one hundred and five. They tend to be
Speaker 2: extremely healthy. Many of them have never seen a doctor
Speaker 2: until they're one hundred or so, and then they suddenly
Speaker 2: go into a decline and die. Now you could ask
Speaker 2: why is that, Well, it could be that they're selected
Speaker 2: and they're just there's a selection bias there. First of all,
Speaker 2: they may be lucky in the combination of genes that
Speaker 2: they have, but they each combination, there's no fixed combination.
Speaker 2: They may be different than each individual, but somehow these
Speaker 2: combinations give them that edge. Another is that they may
Speaker 2: simply have been lucky in avoiding various diseases and cancer
Speaker 2: and accidents and so on. And you're looking at the survivors, okay,
Speaker 2: and so it's not something that's translatable to the rest
Speaker 2: of the population necessarily. So that's still debating. And people
Speaker 2: are studying centenarians, which I think is a great idea,
Speaker 2: and trying to find out more or about their lifestyle
Speaker 2: and their genome and also their methylation patterns and so on.
Speaker 2: Now you asked, what could WeDo, Well, I advocate the
Speaker 2: trio of diet, exercise, and sleep. It's been known in
Speaker 2: many species that caloric restriction improves lifespan and improves health
Speaker 2: in old age. And of course caloric restriction is extreme.
Speaker 2: It means you're consuming just the bare minimum number of
Speaker 2: calories required to have a steady state. In other words,
Speaker 2: you're not losing weight and starving, but you're just steady.
Speaker 2: But that will leave you hungry and cold, and your
Speaker 2: loss of libido and all sorts of side effects which
Speaker 2: maybe not worth it. Yeah, you know, it reminds me
Speaker 2: of that joke about the doctor who said, you know,
Speaker 2: if you do these things, you'll live live longer, and
Speaker 2: the patient said really, he said, well, I'm not sure,
Speaker 2: but it will feel like it so anyway. So, but
Speaker 2: but you could have a moderate diet, you know. And
Speaker 2: it is true that a healthy and moderate diet will help.
Speaker 2: And exercise has all kinds of things, including, by the way,
Speaker 2: those regenerative abilities, regenerating muscle, and even regenerating mitochondria, which
Speaker 2: are these organelles in our cells. So exercise has huge
Speaker 2: benefits that are only now becoming clear. And then the
Speaker 2: third which I think Americans need to take more note off.
Speaker 2: And by the way, I am an American who lives
Speaker 2: in Britain, although I'm now also a British citizen. So
Speaker 2: Americans particularly ignore sleep. Okay, and sleep is really important
Speaker 2: because that is when a lot of the repair and
Speaker 2: maintenance mechanism of the cell, the clear, clearing out garbage,
Speaker 2: you know, repairing damage, et cetera. Much of that occurs
Speaker 2: when we sleep. And there's actually a very nice book
Speaker 2: called Why We Sleep by Matthew Walker, which talks about
Speaker 2: all of the things about sleep. So though that trio
Speaker 2: is extremely healthful. Now, things like stress, cause you know,
Speaker 2: accelerate aging. But you know, if you exercise and sleep,
Speaker 2: you will also be less stressed. And if you exercise
Speaker 2: you'll sleep better, sleep better, you're less likely to overeat
Speaker 2: and you know, snack and so on. So there's it's
Speaker 2: like a three legged stool that help you know, each
Speaker 2: one helps the other two.
Speaker 3: But then let me ask you about that specifically, because
Speaker 3: it feels like as we get older, it's harder to
Speaker 3: sleep longer it is well. And yet you're telling me
Speaker 3: that sleep is crucial for old age, and so it
Speaker 3: seems like a death spiral there exactly.
Speaker 2: And that's why if you exercise and eat well, you're
Speaker 2: more likely to sleep well. And and then it's a
Speaker 2: it's a kind of virtuous cycle. They help each other,
Speaker 2: each each leg help the other two. And then there
Speaker 2: are social things. For example, again, Daniel, you mentioned causation
Speaker 2: versus correlation. But there's strong evidence that people who are
Speaker 2: socially well networked in old age, for example, they have
Speaker 2: circles of friends, family, they're socially involved, tend to have
Speaker 2: lower mortality rates. And people with a sense of purpose
Speaker 2: in life, independently of the social network they have a
Speaker 2: sense of purpose in life also tend to live longer.
Speaker 2: And so this would argue for being socially involved and
Speaker 2: perhaps you know, contributing, you know, maybe volunteering and having
Speaker 2: some sort of purpose just beyond watching your Netflix Q,
Speaker 2: although that some people would argue that's a purpose too,
Speaker 2: but anyway, but having a real purpose in life might help.
Speaker 2: Now again you might say, well, people who are healthier
Speaker 2: and you know, not as fast may be more inclined
Speaker 2: to do these things. So there is this correlation causation issue,
Speaker 2: but I think it's it's well worth considering.
Speaker 1: Is it time for the alien question, Daniel?
Speaker 3: I think it is. So we often wonder on this
Speaker 3: podcast not just about the scientific mysteries here on Earth,
Speaker 3: but scientific mysteries more broadly in the galaxy. And so
Speaker 3: since we're in this moment where we you know, maybe
Speaker 3: on the cusp of discovering aliens on the other planets
Speaker 3: in the next decade or whatever. Do you think that.
Speaker 2: I'm very agnostic about that, by.
Speaker 3: The way, as Ama, I sure, though enthusiastic. But say
Speaker 3: that we're there, you're an astrobiologist, you're on a mission,
Speaker 3: you're landing on the planet. Do you expect that life
Speaker 3: cycles on alien planets will also have the same sort
Speaker 3: of aging patterns that we see here on Earth.
Speaker 2: I think so, because I think natural selection is a
Speaker 2: universal process. You know, if you think of life as
Speaker 2: essentially the ability to reproduce, self, replicate, and evolve are
Speaker 2: two essential characteristics of life. So if you have that,
Speaker 2: you will have natural selection, and so it will if
Speaker 2: inevitably have these trade offs of resource versus maintenance and repair,
Speaker 2: and and of course if it's carbon based, then you
Speaker 2: know it's more likely even to have that. And and ultimately,
Speaker 2: ultimately the laws of physics, which you know are result
Speaker 2: in chemistry, which results in damage that's not going to change,
Speaker 2: you know, somewhere else.
Speaker 3: So everywhere across the galaxy there are grumpy old aliens
Speaker 3: telling those young kids to get off their lawn.
Speaker 2: That that that I would I would bet on that
Speaker 2: if I had to. But I'm I'm somewhat skeptical about
Speaker 2: I think we don't know what the probability of life
Speaker 2: here is, and until we know that, we have no
Speaker 2: idea whether life elsewhere is very likely or whether we're
Speaker 2: alone or somewhere in between. We just don't know. I
Speaker 2: should say some of the enthusiasm for extending lifespan to
Speaker 2: very very long lifespan is by people who want to
Speaker 2: do extra galactic travel. You know, there are people who
Speaker 2: feel that we may be the only intelligent species and
Speaker 2: we should go off and colonize not just Mars, which
Speaker 2: you guys have pointed out as extremely hard anyway, but
Speaker 2: you know, even other galaxies, and so they figure, well,
Speaker 2: if we have to do that, then we have to
Speaker 2: be able to survive the voyage, you know, and so
Speaker 2: we should you know, we need to start working on longevity.
Speaker 2: So it seems like a crazy idea, but anyway, that's
Speaker 2: how it is.
Speaker 1: I think for a lot of people, it's like, you know,
Speaker 1: they'll say, oh, I want humanity to do it, but
Speaker 1: what they mean is that I want to be the
Speaker 1: one who does it in particular.
Speaker 2: So yeah, yeah, yeah, absolutely, yes, all.
Speaker 1: Right, Well, thank you so much for being on the show.
Speaker 1: This was fascinating. I'm sure our listeners are going to
Speaker 1: be thrilled with all of the answers, and thank you
Speaker 1: for your time.
Speaker 2: Thank you, it's been a real pleasure chatting with both
Speaker 2: of you. And by the way, I really enjoyed your book.
Speaker 1: Oh thanks, I loved your book. Daniel and Kelly's Extraordinary
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