Why do we age? (featuring Dr. Venki Ramakrishnan)

30:12So you get the picture. The stem cells are becoming more specialized. But those stem cells have a balancing act. They have to reproduce so that they maintain the stem cell population. but they also have to differentiate and produce more of the tissue. So there's always this switch going on. Do they reproduce more of themselves, so you have more stem cells, or do they make the tissue keep regenerating the tissue they are? And there's always this balance. But as we get older, our stem cells get depleted because they also get defective, they also age, they also become senescent. And so you get this depletion of stem cells.

30:56You also get the remaining stem cells are not optimal. They become what are called clones. Instead of having a diverse population of stem cells as when we're young, you get these clonal stem cells, which are suboptimal. They're selected for being able to reproduce rather than being effective at generating tissue. So these stem cells also decline. So that's why we can't, you know, keep going forever, you know, by regenerating tissue. Now, the other question your listener had was, you know, what about our germ cells? You know, we can, you know, we keep producing babies that are age zero. They're not, you know, in my book, I point out that a 40-year-old woman doesn't give birth to a baby that's 20 years older than a 20-year-old woman.

31:46They're both zero, right? Born at time zero. So that's a combination of two things. One is our germline cells are highly protected against damage. They have better repair mechanisms for repairing DNA damage. They're shielded against DNA damage, et cetera. So that's one aspect. The other is there's a brutal selection process. You know, a female is born, a female human is born with about a million or so eggs. But, you know, if you look at the number of menstrual cycles in a woman over a lifetime, it's only maybe a few hundred. So why do you need a million eggs, you know, when you're really only going to use at the most a few hundred, right?

32:31So that's because there's a lot of selection in the process of going from the germline's precursor cells to the egg that's actually eventually selected for ovulation. There's a lot of selection. Sperm, of course, you know, is highly selected. I mean, you know, in each fertilization event, I don't know how many, I would hate to take a guess, but maybe it's a million sperm cells or something. And out of that, only one is selected, you know, so they have to race and they have to, you know, win the competition. So they are also selected for fitness and for health. And then after the fertilized egg is formed, it is also checked.

33:19So if the developing embryo is at all defective, there'll be spontaneous abortion. Often a woman won't even know it, the very early spontaneous abortion. Later abortions are what we call miscarriages, and that's another selection. And even within the growing embryo, cells are selected against if they're defective. The embryo keeps growing, but it kills off cells that are defective, which I found remarkable. So it's this combination of selection and protection that ensures that, you know, the child that is born has its aging clock somewhat reset, okay, at each generation. But is it technically possible for us to reset our own clock?

34:09Is it just like a bad idea evolutionarily? Or is there something that prevents us from just like constantly being at t equals zero? I don't see how you would reset your entire clock, you know, in the whole organism. There are people, so if I were to back up just a little bit, there is an example of taking a fully grown adult cell and making a whole new animal from it. And the first time that it was done was by John Gurdon, who received the Nobel Prize for it, when he cloned a frog from a skin cell. So he took a skin cell from an adult frog and implanted the nucleus of that cell into the egg of another frog and then just grew it up.

34:56and it resembled the frog from which the skin cell had been taken. You know, so it was essentially a clone. And then people asked, could they do it to mammals? And that made big headlines when Dolly the sheep was cloned. Now, Dolly the sheep turned out to be a very sickly sheep and died at about half the age of a normal sheep. So everybody said, aha, this is because Dolly the sheep was cloned from a fully grown adult cell, which was already kind of old and damaged and wasn't a normally produced sheep. It was done by this weird cloning procedure. But it turns out that there are many other cloned animals.

35:40And in fact, with Dolly, there were other cohorts like Daisy and Debbie. They're all females that had D names. And these sheep, though, by and large, had normal lifespans. And so that means that you could actually reset the clock to a substantial degree by erasing all the marks on the DNA. It's not perfect because the cloning itself involves lots of selection. It's very, very inefficient. It only works a small fraction of the time, and most of them end up in miscarriages or they don't take and so on. So at least in theory, it's possible. Now, could we do to cells in a more systematic way what Dolly the sheep or John Gurdon did with his frog?

36:30Because they just treated it in various ways, but they didn't have a clear idea of what were they doing to make that adult cell go back to resembling a fertilized egg and start growing a new animal. You know, it's like going backwards in time, right? Right. And so a Japanese scientist named Shinya Yamanaka asked, could you take these stem cells that are in the final stage or even the final cells, like a skin cell or, you know, a lung cell or whatever, and have them go all the way back to pluripotent stem cells so that they could then, you know, become any kind of cell. And remarkably, he found that if you take four genes and introduce them into one of these adult cells and turn them on, you could change the genetic program of the cell and have it go backwards, all the way back to pluripotence.

37:31Now, this has created a big industry in the stem cells because stem cells are going to be useful for all kinds of things. For example, if you want to replace damaged tissue, You know, let's say you want to replace pancreas and diabetics so that they can produce insulate. There are all kinds of things being talked about. And there, you know, cartilage in a guy like me with very bad joints. So, or for a guy like me with, you know, very little hair, you could imagine stem cells stimulating new hair growth, okay? And that would be a billion-dollar industry. Yeah, if you could develop some, like, gun, you point at a part of your body and you're like, make this younger.

38:10Exactly. So people asked, now the problem with going all the way back is that you have the risk of cancer, you know, because you're taking these cells, they're not quite exactly the same as a normal embryonic development is. It's the somewhat artificial process that you're using to go backwards in development. And when they try to grow those pluripotent stem cells, They often would get these tumor-like growths called teratomas. And so there is definitely a cancer risk. But what a number of scientists asked was, supposing you turn on these Yamanaka factors transiently, you know, just turn them on and then figure out a way to turn them off after a while.

39:02Then what would happen? Well, astonishingly, they tried this in mice, and they found that the mice, you know, resembled younger animals. They suddenly had better fur and muscles, and, you know, by various markers, they seemed younger. So this idea of cellular reprogramming is a big area in the longevity field, but it's still in early stages. Even though there's a lot of excitement, the idea that tomorrow you're going to go and get a treatment that will suddenly make all your cells younger, it's really not going to happen anytime soon. And it's because there are lots of problems. One is, you know, you have to get the right dose.

39:49You have to make sure it's safe. You have to make sure it goes to the tissues in just the right amounts. These are all big, challenging problems. And, you know, of course, a long-term cancer risk is another problem. So I think it's very exciting and promising, but it's not something that's around the corner as it's often hyped. I mean, that's my opinion. Of course, you know, people will disagree with me. But remember, a lot of these people have quite a lot of skin in the game. They have financial interests. They've founded companies and so on. So you have to slightly take what they say with a pinch of salt.

40:30So you've mentioned that one of the reasons that we age and die is because it has something to do with resources and – With evolutionary choice, basically. Yeah. So now many humans like me live in an environment where there are too many resources maybe and we should take in fewer resources. And we live in an environment where we're getting better and better at being able to treat cancer because it seems like we keep coming up across cancer as the thing that's holding us back. So if we were in a high-resource environment and we could figure out how to cure cancer, do you think we might be able to get our lifespans up 100 years or something?

41:07Well, somebody did a calculation, a demographer named Jay Olshansky from Chicago, who's a leading expert in this area. He did a calculation a number of years ago, maybe 25, 30 years ago, which suggested that there are four major causes of major diseases of old age that cause death. One, you mentioned cancer. The other one is diabetes. A third one is heart disease. And the fourth one is dementia, neurodegenerative diseases. And of course, the neurodegenerative diseases are among the hardest to treat. But let's say you could eliminate all four of them. The suggestion is you would only gain about 15 years of lifespan if you eliminated all of these four causes.

41:58And the reason is that they will not affect the normal process of aging, you know, which leads to frailty of, you know, system-wide frailty. And there's always this argument, is aging a disease? And people say, well, you know, all of these major things like diabetes, cancer, et cetera, the risk goes up with age. In fact, the biggest risk factor is age. The older you are, the more likely you are to get one of these things or more of, or several of them. But the other argument is that, well, these diseases don't happen to everybody. Not everybody dies of cancer. Not everybody has heart disease. And also young people get cancer.

42:41So it's not directly related. And aging, on the other hand, is something that happens to every single person and it's inevitable. So how can you call something that's both ubiquitous and inevitable a disease? It's simply a process of life. And I tend to agree with that. But the reason they want to call it a disease is because then it's easier to get approval for clinical trials. Well, I think they ought to try some other thing. For example, they can choose a target, a disease target that's strongly correlated with aging. For example, osteoarthritis or loss of various functions and so on. And then they could use that as the measure of success of their drug.

43:31So there are ways to get around it. But I don't think that just eliminating these diseases will increase lifespan that much. And in fact, even people who in the aging field who have bet, so Olshansky was on one side of a bet with another gerontologist named Stephen Ostad. Stephen Ostad made a bet with him that the person who lives to be 150 has already been born, And that bet was made some time ago, and they bet it so that in 150 years, the amount would be worth, I don't know, a billion dollars or something. Of course, maybe it'll cost a billion dollars to buy a sandwich by that time. But anyway, but they made this bet.

44:19Now, Stephen Ostad also doesn't believe that it's just going to be because of eliminating disease. Rather, what he thinks is that we're making progress in slowing down or arresting aging itself, and that's the reason why we may end up living longer. And, for example, there's a drug called rapamycin, which is related to caloric restriction, which also allows animals to live longer. That, for example, can increase lifespan in mice by 20 or 30 percent. Well, if we live 90 years, 30 percent of that would already get us to 120 or so, you see. So maybe he's counting on things like that. I tend to be on the Olshansky side.

45:10I think that really fundamentally increasing lifespan and especially healthy lifespan is not going to be as easy as they say because it's highly multifactorial. There are so many things going on. Well, how do we know you're not just a shell for big death? You know, are you being paid by the death industry? All right. Well, we'll take a break. And when we get back, we'll talk more about aging.

45:49Hey, everyone. It's Cal Penn, host of Earsay, the Audible and iHeart audiobook club. This week on the podcast, I'm sitting down with Divergent author Veronica Roth to talk about her sprawling new novel, Seek the Traitor's Son. It's a sci-fi fantasy epic about two protagonists on opposite sides of a war and a prophecy neither of them wanted. My first book was Divergent. And when that came out, like, because it was so popular, I think it attracted like mostly positivity, but the negativity I sucked in like a sponge. And I think it was like critiques of things I liked when I was like, you know, I was 23 and I wrote this book and it had all my like dorky little cheesy or maybe unrealistic loves in it.

46:31And I started to feel a lot of shame about those things. And so for the rest of my career, I steered away from those little things that like make you feel pleasure when you read. But I also was like saying no to these parts of myself that I then was like, screw it. So that's this book. Listen to Earsay, the Audible and iHeart Audiobook Club on the iHeart Radio app or wherever you get your podcasts. Aging is real. And so are the benefits of adding Vital Proteins Collagen Peptides to your daily routine. Because around the age of 30, your body needs backup to keep your collagen up. To help support healthy hair, skin, nails, bones, and joints.

47:12Available in the classic collagen peptides. Collagen and protein shakes. And new Vital Proteins Collagen Sparkling Waters. So you can stay vital, stay you. Visit VitalProteins.com to learn more and where to buy. These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Apple Vacations, where your story starts. The July Savings Event from Apple Vacations is here. Book by July 23rd and save up to$400 off your flight and hotel package to Mexico, the Caribbean, Central America, Hawaii, or Europe. From all-inclusive escapes to bucket list adventures, Apple Vacations makes it easy to create memories with the people who matter most.

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48:41And we're back. So we have another question from a listener, and here it is. I'm curious why immune systems seem to decline with age. Shouldn't they get supercharged? because by then, when you're old, you've basically seen everything. It is true that immune systems are exposed to more things as we age, but immune systems are essentially a collection of cells, and the cells themselves age, and so they don't respond as well as they do when we're younger or when we're in our prime. And this has to do with molecular damage affecting higher levels like the cell and communication between cells. And so for all kinds of reasons, our immune system, as a result of this accumulated damage, doesn't function optimally.

49:36So it's got a lot more wisdom, but like less energy and effectivity. Yeah, and actually it doesn't function as well. For example, it responds in an aberrant way. It's not as well regulated. The immune system always has to be very finely regulated because you don't want to react against yourself or against harmless things. You only want to react against truly dangerous entities. So that fine balance is disrupted. And so you get essentially a dysfunctional immune system. and you also get a lot of inflammation as a result. So, for example, I mentioned those senescent cells. The reason those senescent cells secrete inflammatory compounds is as a signal to the immune system that, hey, there's something wrong here.

50:24Come and clear it up. And so the immune system will come there. It may be the site of a wound or an infection or some other stress, and it will deal with it. But as we get older, and not only do the number of senescent cells increase, but the immune system doesn't respond as well to the signals. And so you get this sort of autocatalytic or you get this essentially this explosion in the growth of some senescent cells and inflammation. And is this something that's understood across species? One of the listeners asked why cats and dogs have the same age-related diseases that we do, but they appear at a younger age, maybe a smaller number of years.

51:10That's simply the fact that this allocation of repair to maintenance and repair to growth and reproduction, that balance is different for different species. You know, you could ask, why do whales live so long? Well, one reason is they have a slower metabolism than, say, an animal like a mouse. But the other reason also is that they have a large number of repair enzymes. If you look at just DNA repair enzymes, they have many different repair enzymes when they sequence the genome of some of these species. And elephants, for example, have many more copies of a DNA repair enzyme than mice do. Because they live longer, so they need more repairs.

51:57Yeah, and they have to maintain that. And also, there is a paradox. They have many more cells. And so the chance that one of their cells could become cancerous and kill the whole animal is much higher in a larger animal than in a small animal. But paradoxically, it's mice get cancer more often than elephants. And that's because the elephants do have this additional capacity to repair. So it's all evolution really just optimizing for fitness. Remember, evolution does not optimize for long life. It doesn't care about long life. It cares about survival of genes because that's what it selects for.

52:39This might be a little too far off topic, but I've seen articles that say like, green sharks never get cancer. Are there actually species that never get cancer or it just takes them away and we don't see it often? It is almost entirely that we don't observe them long enough. So, for example, I'll give you an example, Galapagos tortoises, right? You know, they live to be 200 years old. And I like to joke that there's probably a Galapagos tortoise wandering around now that might have actually met Darwin. Oh, that's a cool thought. Right. But anyway. Let's have them on the podcast. Exactly. So, you know, if they could talk, they might be able to tell you quite a bit.

53:18But anyway, now it was thought for a while that these tortoises don't age. Well, actually, they do age. If you look at old tortoises, they have terrible eyesight and, you know, they're slow moving. Their skin's, you know, old. You know, they have all these. They don't know how to use the VCR. Exactly. They have all of the same problems. And it's just that it happens more slowly. Okay. And I got to say, Daniel, I think the VCR joke aged you more than anything. Well, the fact that you laughed at it aged you. Oh, you got me. That's true. That's true. So let's jump back, if that's OK, to another example of folks trying to extend lifespan.

54:00So I've heard of examples of like taking blood from young mice and giving it to old mice. And then I think there's a guy, Brian Johnson, who's trying to limit aging by using his son's blood. Is there any evidence that that's anything other than nuts? That's an excellent question. question. And it is true that when they connected an old rat to a young rat, the old rat benefited by the exchange of blood. And the young rat actually suffered. And then they were wondering whether it was really due to the blood itself, or maybe the young rat had better liver and kidneys to detoxify the blood. And so it wasn't just the blood, but it was just that it had better organs to clean up blood.

54:44So they separated them and simply gave them transfusions. And they found that, in fact, the effect was still there, but it was more that the old rat had things in it that were harmful to the young rat. That was more the case than that the young blood was beneficial to the old rat. But it did. There was some effect both ways. Now, this is true. And when the people discovered it, they got all sorts of creepy phone calls from rich people asking, you know, whether they could get young blood and so on. And in fact, companies... Where do I buy babies? This kind of stuff. Exactly. And in fact, companies sprouted up.

55:28And as you can imagine, mostly in California, I think. What? That's what I would have guessed. You mean the center of innovation and forward thinking and creativity. That's why you said Teleformia. Anyway, I'm somehow obsessed with youth. But anyway, some of these companies would get blood from young donors and sell them at a huge markup to rich people who wanted them. And in one case, the FDA actually tried to shut a company down and then it opened up under a different name. And in one case, the CEO said, well, look, our people simply don't have the time to wait for clinical trials, you know?

56:13Oh, my goodness. It was really bizarre coming from, you know, a CEO of a health-based company. But you're saying that there are real benefits to having transfusions of blood from young people. Well, there certainly seem to be in animals. And so there's a big body of research to find out what is changing in blood as we get older. And what do these factors do? You know, if they're harmful in old age, what do they do? Maybe we can inhibit them. Or if they're beneficial in early life, maybe we can take advantage of that and introduce them into older people. So I think that's a very legitimate and broad area of research, and lots of very top scientists from very well-known universities are actually working on that.

57:09But this idea that you should just take transfusions, it's not really going to help that much at this point. And Brian Johnson, whom you mentioned, actually did this experiment of keeping it all in the family. He took blood from his son and gave his blood to his dad. But he's also, I mean, to give him some credit, he's obsessed with aging, you know, or not aging, to be more precise. He spends like a couple of million dollars a year on all kinds of longevity treatments and measurements and, you know, probably has, you know, fitness programs and all sorts of things. Okay. Well, the thing that fascinates me about Brian Johnson is that he does take a lot of data, right?

57:55Exactly. He is focused on these metrics, right? He's focused on metrics. But he doesn't look young. Like, even though he says he has all these metrics which are equivalent to an 18-year-old, he still looks like a vampire. So he sort of captures this, like— Well, I would say—no, no. I'll give him credit. He's in his late 40s. He looks pretty good for late 40s. But I'll tell you, my son is in his late 40s. Yeah. does none of this stuff, okay? But he runs regularly and eats well. And he looks just as good as Brian Johnson. And I'm not just being biased. You could look him up online. He's a cellist.

58:31Well, you're definitely biased, but I don't not believe you. But I think it raises a deeper question, which is like, is it possible to be young biologically by all of these metrics? As you say, you're measuring the damage to whatever molecular mechanisms, but still somehow not be young in the sort of social sense? That's a very good question. You know, so, you know, I mentioned the high school reunion and how we all look different. Yeah. So that's led to this quest for biological markers of age, okay? Yeah. Because you want to know, you know, your birthday may have been, you know, 40 years ago, but how old are you really in biological terms, right?

59:12So the people have come up with different clocks, you know? So one clock is this so-called DNA methylation clock. So these are little tags that get attached to our DNA from the time we're conceived. It happens even in utero. We're aging even in utero. And that's apparently better correlated with mortality than chronological age. You know, so chances that you're going to die are more correlated with your DNA methylation than they are with your date of birth. So that's, you know, used as a clock. But does that suggest that if you could somehow adjust that, you would extend your life? I mean, is it causal or is it correlated?

59:56That's the real question. You know, we don't know the extent of causality. The other case is that as we age, extra sugar groups get added to our proteins. It's called glycation. And so you can measure this addition of sugar groups to our proteins. And when that happens to our proteins of our immune system, it also doesn't work as well. So people think that it has some connection with this decay of the immune system. But anyway, that's another clock. Now, people will sell you kits. They'll tell you a DNA methylation kit or a glycation kit or a full blood, you know, library, you know, they'll just analyze a bunch of stuff in your blood to give you a sort of biological age.

1:00:47And each one will say this is our thing is the most accurate. Now, I think these are all very useful research tools because if you have a longevity intervention, like an anti-aging intervention, you can see, are these markers changing more slowly or are they changing at the same rate? That'll give you a good idea of are you aging faster or not. But people need to come together and agree on a panel. you know i don't think a single clock is going to tell you the whole story yeah okay i think they need to agree on a panel and then say uh okay here's a panel and this is what it represents and it might be a complex thing there's no point in talking about your biological age because your liver may not be the same age as your kidney or your lung you know you can imagine if you're an alcoholic, your liver might be older than other parts of your bodies.

1:01:49So I think people need to have a more complex view of aging, of biological age. But don't we also need to unravel this question of causality? I mean, if you identify a marker or even a complex panel that indicates biological age, adjusting those results doesn't necessarily make you younger. It's like, I can turn back the clock literally and it will read a different number, doesn't make me younger. And If I could just comment one more thing, which is one of my favorite mechanisms that Brian Johnson keeps track of is that, and I love that he's so transparent about his data, is that he measures his erection quality during the night.

1:02:26And he posts this data online, which I think is hilarious. But, you know, just as an easy example, if the guy took a Viagra every night when he went to bed, he probably would have like glorious erections all night long. It wouldn't make him any younger, right? That's true. But, you know, let's take DNA methylation. You know, so one of the things about those reprogrammed cells is that they have changed the methylation pattern as well. You know, so, I mean, one of the distinct things about going back to an early embryonic state is that the methylation pattern is different. So there may be some element of causality because methylation does change the program of our gene expression.

1:03:11So if you're going back to an earlier state, maybe you're going back to an earlier program. But I agree that causality needs to be established by careful experiments. Is it sufficient to reverse methylation, and would that automatically cause something to look younger? There are some scientists who claim that they have reversed aging just by this process, but it's highly controversial. So I imagine our listeners are going to want to know, as an expert in aging who doesn't believe, you know, that there's a magic pill out there that's going to give us an extra 50 to 100 years, what do you do to slow the aging process?

1:03:55Yeah. Yeah, I should say, you know, there's no theoretical reason why we couldn't all start living to be 150 eventually, okay? The thing that I'm – what I'm saying is that we don't know how to do that at this point. And more importantly, we don't know how long it's going to take. And that's where I differ with some of the more extreme optimists that the field is full of, okay? But what we can do right now, before that, I wanted to address one question. If you ask most aging researchers, they would say, oh, we're not interested in extending lifespan. We're really interested in extending healthspan.

1:04:42And this whole thing is based on an idea called compression of morbidity. So as we get older, we start accumulating various morbidities. You know, you could say diabetes is one or heart disease or dementia, cancer, et cetera, you know, frailty of various kinds or morbidities. And the ideal life would be that you're extremely healthy and then suddenly undergo a rapid decline, okay? This is called compression of that morbidity into a very short space of time, you know, span of time. So that's the goal. the question is, is that even possible? Well, in the last few decades, we are all living healthier as a result of improvements in health, but it's also extended our lives so that our period of morbidity has not changed.

1:05:37Okay. So it's just postponed it. And in fact, you know, we're living more years in its sort of decline than, you know, whereas before we might have died brutally quickly, okay, as soon as something went wrong, you know, would collapse and die. Now we're sort of prolonging it and have a long period of morbidity. So it's not clear that as we improve things, we're going to somehow keep healthy and reach some fixed limit and then collapse. It may simply be that we'll live a bit longer and still have that inevitable period of decline. That's an unsolved question, no matter what people will actually say.

1:06:23The one exception to this are super centenarians. These are people who live to be over 110 and even over 105. They tend to be extremely healthy. Many of them have never seen a doctor until they're 100 or so. And then they suddenly go into a decline and die. Now, you could ask, why is that? Well, it could be that they're selected and there's a selection bias there. First of all, they may be lucky in the combination of genes that they have, but each combination, there's no fixed combination. They may be different in each individual, but somehow these combinations give them that edge. Another is that they may simply have been lucky in avoiding various diseases and cancer and accidents and so on.

1:07:17And you're looking at the survivors, okay? And so it's not something that's translatable to the rest of the population necessarily. So that's still debating. And people are studying centenarians, which I think is a great idea and trying to find out more about their lifestyle and their genome and also their methylation patterns and so on. Now, you asked, what could we do? Well, I advocate the trio of diet, exercise, and sleep. It's been known in many species that caloric restriction improves lifespan and improves health in old age. And of course, caloric restriction is extreme. It means you're consuming just the bare minimum number of calories required to have a steady state.

1:08:09In other words, you're not losing weight and starving, but you're just steady. But that will leave you hungry and cold and loss of libido and all sorts of side effects, which maybe not worth it. It reminds me of that joke about the doctor who said, you know, if you do these things, you'll live longer. And the patient said, really? He said, well, I'm not sure, but it'll feel like it. So anyway, but you could have a moderate diet, you know, and it is true that a healthy and moderate diet will help. And exercise has all kinds of things, including, by the way, those regenerative abilities, regenerating muscle and even regenerating mitochondria, which are these organelles in our cells.

1:08:58So exercise has huge benefits that are only now becoming clear. And then the third, which I think Americans need to take more note of, and by the way, I am an American who lives in Britain, although I'm now also a British citizen. So Americans particularly ignore sleep, okay? And sleep is really important because that is when a lot of the repair and maintenance mechanism of the cell, the clearing out garbage, you know, repairing damage, et cetera, much of that occurs when we sleep. And there's actually a very nice book called Why We Sleep by Matthew Walker, which talks about all of the things about sleep.

1:09:45So that trio is extremely helpful. Now, things like stress cause, you know, accelerate aging. But, you know, if you exercise and sleep, you will also be less stressed. And if you exercise, you'll sleep better. If you sleep better, you're less likely to overeat and, you know, snack and so on. So it's like a three-legged stool that each one helps the other two. But then let me ask you about that specifically, because it feels like as we get older, it's harder to sleep longer and to sleep well. And yet you're telling me that sleep is crucial for old age. And so it seems like a death spiral there.

1:10:22Exactly. And that's why if you exercise and eat well, you're more likely to sleep well. And then it's a kind of virtuous cycle. They help each other. Each leg helps the other two. And then there are social things. For example, again, Daniel, you mentioned causation versus correlation. But there's strong evidence that people who are socially well-networked in old age, for example, they have circles of friends, family, and they're socially involved, tend to have lower mortality rates. and people with a sense of purpose in life, independently of the social network, they have a sense of purpose in life, also tend to live longer.

1:11:06And so this would argue for being socially involved and perhaps, you know, contributing, you know, maybe volunteering and having some sort of purpose just beyond watching your Netflix queue. Although some people would argue that's a purpose too. But anyway, but having a real purpose in life might help. Now, again, you might say, well, people who are healthier and, you know, not aging as fast may be more inclined to do these things. So there is this correlation causation issue. But I think it's well worth considering. Is it time for the alien question, Daniel? I think it is. So we often wonder on this podcast, not just about the scientific mysteries here on Earth, but scientific mysteries more broadly in the galaxy.

1:11:54And so since we're in this moment where we, you know, may be on the cusp of discovering aliens on other planets in the next decade or whatever, do you think that... I'm very agnostic about that, by the way. As am I, sure, though enthusiastic. But say that we're there. You're an astrobiologist. You're on a mission. You're landing on the planet. Do you expect that life cycles on alien planets will also have the same sort of aging patterns that we see here on Earth? I think so, because I think natural selection is a universal process. You know, if you think of life as essentially ability to reproduce, self-replicate, and evolve, those are two essential characteristics of life.

1:12:37So if you have that, you will have natural selection. And so it will inevitably have these trade-offs of resource versus maintenance and repair. And of course, if it's carbon-based, then it's more likely even to have that. And ultimately, the laws of physics, which result in chemistry, which results in damage, that's not going to change somewhere else. So everywhere across the galaxy, there are grumpy old aliens telling those young kids to get off their lawn? I would bet on that if I had to. But I'm somewhat skeptical about, I think we don't know what the probability of life here is. And until we know that, we have no idea whether life elsewhere is very likely or whether we're alone or somewhere in between.

1:13:36We just don't know. I should say some of the enthusiasm for extending lifespan to very, very long lifespan is by people who want to do extragalactic travel. There are people who feel that we may be the only intelligent species and we should go off and colonize not just Mars, which you guys have pointed out as extremely hard anyway, but even other galaxies. And so they figure, well, if we have to do that, then we have to be able to survive the voyage, you know. And so we should, you know, we need to start working on longevity. So it seems like a crazy idea. But anyway, that's how it is. I think for a lot of people, it's like, you know, they'll say, oh, I want humanity to do it.

1:14:23But what they mean is that I want to be the one who does it in particular. Oh, yeah, yeah, yeah. No, absolutely. All right. Well, thank you so much for being on the show. This was fascinating. I'm sure our listeners are going to be thrilled with all of the answers. and thank you for your time. Thank you. It's been a real pleasure chatting with both of you. And by the way, I really enjoyed your book. Oh, thanks. I loved your book.

1:14:49Daniel and Kelly's Extraordinary Universe is produced by iHeartRadio. We would love to hear from you. We really would. We want to know what questions you have about this extraordinary universe. We want to know your thoughts on recent shows, suggestions for future shows, If you contact us, we will get back to you. We really mean it. We answer every message. Email us at questions at danielandkelly.org. Or you can find us on social media. We have accounts on X, Instagram, Blue Sky, and on all of those platforms, you can find us at D &K Universe. Don't be shy. Write to us.

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