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

Daniel and Kelly get answers to listener questions about why we age from Dr. Venki Ramakrishnan, author of "Why We Die: The New Science of Aging and the Quest for Immortality". See omnystudio.com/listener https://omnystudio.com/listener for privacy information.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Daniel Whiteson?

  This is an iHeart Podcast. Guaranteed human.

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• 1:11Kelly Weinersmith?

  They say that only two things in life are certain: death and taxes. For the lucky among us, we'll pass away quietly at an old age. But why is aging, and thus death, inevitable? And how do we even define aging? Yes, you can define it by the ticking of the clock, but is there a biological way to define it that gives you a better shot at really understanding how the passage of time has worn away at your body? If two people in their 30s can mix their old cells together to make a brand-new baby, then why can't those same two people just start making young cells for themselves? And shouldn't evolution favor living a really long time

• 1:54Kelly Weinersmith?

  so we can make more babies and be around to help them grow? Aging can be a counterintuitive phenomenon, and Daniel and I get many questions from our audience, the extraordinaries, about the aging process. However, despite the furrows in my forehead that get deeper each year and that my son sometimes stares at, this biologist is not an expert in the science of aging. But lucky for us, we were able to get Dr. Venky Ramakrishnan, author of Why We Die: The New Science of Aging and the Quests for Immortality, to come onto the show to answer your questions. Welcome to Daniel and Kelly's extraordinarily old universe.

• 2:49Daniel Whiteson?

  Hi, I'm Daniel. I'm a particle physicist. I round my age up to 100.

• 2:54Kelly Weinersmith?

  Hello, I'm Kelly Wiener-Smith. I study parasites and space. And Daniel, last time we talked, you rounded up to 50. Have you just decided that now that you're 50, you're rounding up to 100? Because that is not a helpful way to round.

• 3:08Daniel Whiteson?

  I think that's totally consistent. When I was 48, I called myself 50. And now that I'm 50, I got to round up to 100. It totally makes sense.

• 3:15Kelly Weinersmith?

  Not to me.

• 3:16Daniel Whiteson?

  Plus, I think I look pretty good for 100.

• 3:18Kelly Weinersmith?

  You look great for 100. But and I said, you look good for 50, too. But like, I don't, yeah, I know that that kind of rounding doesn't make sense to me. But that's all right.

• 3:27Daniel Whiteson?

  All right. So here's my question for you today, Kelly. If you could take a pill that would extend your life to 1,000 years or a million years, would you? Do you want to live a super crazy long life?

• 3:40Kelly Weinersmith?

  All right. So one, okay, so selfishly, I would need to know about the quality of that life. And if the quality of my life was going to be as good it is now for all of that time, I would think about it. But to be honest, the only reason I'm thinking that I might want to say yes is that I want to live at least as long as my son lives, because he's going to need care his whole life. And I don't want him to ever be alone. And so if I could live as long as he lives, 100%. So what about you?

• 4:07Daniel Whiteson?

  No, I see life is like a hike. You know, hikes are wonderful. There's wonderful moments. You're glad you went on them. You're also glad when they're over. Nobody wants to be on a hike that lasts until the end of the universe. And maybe sometimes the best part of a hike is when you get to sit down at the end, you're like, oh, wow, what a nice walk.

• 4:26Kelly Weinersmith?

  Done. Especially at the end of a good hike.

• 4:28Daniel Whiteson?

  Yeah.

• 4:29Kelly Weinersmith?

  You, you're like, ah, all right, I'm ready to be done.

• 4:31Daniel Whiteson?

  Exactly.

• 4:32Kelly Weinersmith?

  And my grandpa passed away recently, and I think he had that kind of life. He like, he hiked, it was a good trip. And at the end, he told everyone, he's like, I'm ready. And then he passed away into sleep. And I was like, man, I really hope that's in the genes somewhere. Cause that's pretty solid.

• 4:47Daniel Whiteson?

  And I hope that listening to this podcast has improved that everybody's quality of life out there. We're making your hike through life more pleasant.

• 4:54Kelly Weinersmith?

  Maybe it will improve their quality of sleep, which at the end of the episode, we'll discover is an important part of being healthy. So we're doing our part.

• 5:03Daniel Whiteson?

  You're saying that listening to the podcast could technically scientifically extend your lifespan.

• 5:08Kelly Weinersmith?

  Um, maybe, maybe. Listen to our prior episodes about how you evaluate scientific statements and see what you think, dear listeners.

• 5:18Daniel Whiteson?

  Mm hmm. And whether you should believe people who have skin in the game. Exactly.

• 5:22Kelly Weinersmith?

  Yes. All right. Well, so we get loads and loads of questions about aging from the extraordinaries. And so I pulled them all together. We found an amazing expert to answer the questions. Amazing. He does such a great job.

• 5:34Daniel Whiteson?

  How do you know this Nobel Prize winner, Kelly? Tell us.

• 5:36Kelly Weinersmith?

  Oh, thanks for pitching, Mike. We both were on the shortlist for the Royal Society Book Prize.

• 5:43Daniel Whiteson?

  Oh.

• 5:44Kelly Weinersmith?

  Yep. Why We Die is Venky Ramakrishnan's book and A City on Mars was my book. And we, we both made the shortlist for the Royal Society Prize.

• 5:52Daniel Whiteson?

  And you're just going to omit those crucial pieces of information that you won the prize. So Kelly is the author of a book which edged out a Nobel Prize winning nonfiction science book.

• 6:02Kelly Weinersmith?

  I was not gonna mention that. It's thank you for all of your support over the years. I appreciate it.

• 6:10Daniel Whiteson?

  All right, well, this is a wonderful conversation with a deep expert who also has the unusual quality of being able to explain things clearly.

• 6:19Kelly Weinersmith?

  Yes, and being so nice, so nice. Yeah, anyway, so I had so much fun. I feel so lucky we got to do this interview.

• 6:26Daniel Whiteson?

  Before we bring on our expert who won a Nobel Prize in this area, we asked you guys what you thought was the reason for aging. Here's what people had to say.

• 6:36Speaker 04

  I understood it to be oxidative pressures where new copies of things just aren't quite as good as they used to be, and there are errors throughout. Short answer, telomeres. Real answer, so that there's someone to say, I wouldn't do that if I were you.

• 6:50Daniel Whiteson?

  To the younger generations, it's not like the clouds are going to yell at themselves.

• 6:54Speaker 05

  Certain proteins that mark our cells or do something along the lines of maintaining how our DNA gets repeated or transcribed, degrade over time. The body forgets how to make new body the way that it once did.

• 7:12Speaker 04

  We age as a consequence of too many gas station burritos, 99 cent big gulps, and betrayal by Telomere.

• 7:19Speaker 06

  At a molecular point of view, it's really hard to maintain consistency in the gazillion times molecules and the cells needs to reproduce. These errors keep stacking up until the whole body decays.

• 7:32Speaker 07

  My short answer is we age due to the passage of time.

• 7:35Speaker 08

  I think we age because we need to die ultimately. I think it's conducive, if not crucial, to the evolution of life itself for organisms to have a finite lifespan.

• 7:47Speaker 09

  Every beginning has an end. So I believe I've read somewhere that the reason why we age is because there is a shortening of some kind of a protein or molecule within our cells.

• 8:01Speaker 10

  The ends of our DNA kind of fray and just gets left up to entropy.

• 8:09Speaker 06

  Aging and death are just part of the evolutionary process and processes that have brought us to where we are today. It's just a fact.

• 8:17Daniel Whiteson?

  Thanks, everybody, for your speculation on this concept. Now let's talk to the expert and find out what we know and what we don't know.

• 8:25Kelly Weinersmith?

  Dr. Venky Ramakrishnan was initially interested in physics, but I'm going to go ahead and give a point to biology because he transitioned to focusing more on this field. And the biology stuff worked out well for him because in 2009, he received a Nobel Prize for his work on ribosomes. He was president of the Royal Society from 2015 to 2020 and recently wrote the book, Why We Die: The New Science of Aging and the Quest for Immortality. And today we'll be talking about the science of aging. Welcome to the show.

• 8:54Speaker 11

  Thank you, and thank you for having me.

• 8:56Kelly Weinersmith?

  Yeah, we're super excited to have you. We get so many questions from our audience about aging and every time I'm like, look, I know when you look at me, I look like the right person to ask about questions about aging, but.

• 9:06Speaker 11

  Well, they should look at me then.

• 9:10Daniel Whiteson?

  And there's so much discussion out there about aging and how to prevent it. And if it's possible and so much snake oil being sold out there. It's so important to cut to the chase.

• 9:19Speaker 11

  It's certainly having a moment and I I'm a little bit cynical. I think it has to do with my generation, the boomer generation that's used to having everything it wanted in life, suddenly coming to terms with getting old. And and so, you know, there's a lot of anxiety in the air. Although, having said that, you know, this fear of death and fear of aging is simply as old as humans, you know, because ever since we learned about mortality, we've fretted and worried about it. And and I like to say, we may be the only species that's aware of mortality.

• 10:03Speaker 11

  Other animals maybe are aware of death, but they they're not aware that they all have a finite lifespan and everybody's going to die. I'm not sure that other species have that understanding that we do. And when we somehow obtained that understanding, perhaps as a result of cognitive development, language and so on, ever since then, it has become, it became a theme. And if you look at most religions, they're all about, you know, how to deal with death and what happens after we die.

• 10:40Kelly Weinersmith?

  Yeah, I don't know if it's a blessing or a curse that our species is aware of that.

• 10:44Speaker 11

  Yeah. I mean, many species aren't even aware of death, you know, it just simply happens.

• 10:50Daniel Whiteson?

  Well, can I start us off with a very broad sort of philosophical question, which is how do you define aging biologically? Because as a physicist, I might think, well, you have a clock and it starts and it stops and that's your age. But we're interested in more than that, right? It's some sort of like decrease in the quality of life. You're gradually moving towards death. It's this fact that you don't just like live for 62 years and then poof, you're done. Your body degrades. How do we define aging in a crisp way scientifically?

• 11:21Speaker 11

  Yeah, so it's not, it's definitely related to the chronological clock to time. But the rate is very different, not only for species, it's vastly different for species, but it's also different for individuals within a species. If you go to your high school reunion, you will immediately be aware of that, the fact that people don't age at the same rate. And I think aging, molecular biologists would define it as the gradual accumulation of changes and damage to us over time. That can happen at different rates in different individuals. And it's not just damage.

• 12:06Speaker 11

  Some of it is changes that occur with with time. It may occur at different rates in different individuals. And these changes may have a purpose early in life. For example, modifications of our DNA. But they cause us, or at least they're strongly correlated with aging later in life. So that's how I would define it. And this this accumulation of changes and damage leads to a gradual loss of function. And when that loss of function reaches some point where some critical system fails, then you have death.

• 12:50Speaker 11

  And so death is a result of aging, but its exact moment can't be predicted because in a complex system, you can't predict exactly when a critical component will fail.

• 13:03Daniel Whiteson?

  And so aging and changes, but that must mean very different things to different parts of your body. You're talking about your nerves, or your skin, or your eyes. Are there ways we have to measure it?

• 13:15Speaker 11

  It happens at every level. It happens at every level, but I would say fundamentally, it happens at the molecular level. And that then manifests itself in each increasing level of complexity. So you can go from molecules to collection of molecules in our cell, to components of the cell, to cells themselves, and then entire tissues and and, you know, the way cells communicate with each other, like our immune system. So you can see that. You know, it happens at the molecular level, but it starts manifesting itself at increasingly higher levels, you know, until a point that, you know,

• 13:59Speaker 11

  we see aging as various forms of frailty. You know, so in fact, a very good measure of aging is actually something called the frailty index. They'll measure things like can you get out of bed? How fast can you walk, you know, 50 yards? What's your grip strength? How good is your eyesight? How good is your cognition? How good, you know, how good is your memory? So all of those things are indications of frailty at a macroscopic level, at a level that you and I experience. But ultimately, the underlying causes are molecular.

• 14:36Kelly Weinersmith?

  Okay, and is aging universal? So we're getting to one of our first listener questions right now. One of our listeners noted that they had heard stories about immortal organisms and they wanted to know, are they actually immortal?

• 14:49Speaker 11

  Yeah, I had to say, there's a lot, a lot of hype. What happens is people will study an organism that ages very slowly and suddenly they'll say, oh, this has no sign of biological mortality. So let me back up and explain what I mean by that. So in normal species, the likelihood of that we are going to die at any given time keeps increasing exponentially. So for example, the chances that you'll die when you're 10 are very small, but the chances you'll die in the next year, when say you're 95 or 100, are almost 50%, okay? So the chances keep going up.

• 15:33Speaker 11

  Now, in some organisms, it appears that that likelihood of dying, you know, of aging events, not of being eaten by a predator or starving or anything else, those are called external causes. But, you know, aging, just dying of aging. That probability doesn't seem to go up with time. And so there are some species like a freshwater species called the hydra. There's another species called the immortal jellyfish. And these tend not to show any signs of biological aging. That is, the likelihood it's going to die just doesn't seem to change with time.

• 16:18Speaker 11

  But in fact, what is happening is it's probably aging very, very slowly. So if you looked, if you simply followed a hydra in the wild, it'll die of some other cause, not of old age. But if you kept it safe and followed it long enough, you will find that it too gradually ages because no regeneration is perfect. You know, the reason hydra and jellyfish appear not to age is they constantly regenerate their tissue using specialized cells called stem cells. In a way, they're like plants. You know, plants have stem cells all over themselves. And that's why you can take a cutting from a plant

• 17:00Speaker 11

  and, you know, grow an entirely new tree with it, right? We can't do that. But, you know, some animals regenerate like starfish. You know, it cut off an arm and it'll regenerate an arm. And, you know, some of these species can regenerate, you know, any tissue. And, uh, but they're, but it's not perfect. And so I would say to your listener that yes, everything will die, but they die at different rates. Okay. I mean, they age at different rates.

• 17:29Daniel Whiteson?

  And so everything ages. It's universal across organisms. Do we understand why we age?

• 17:35Speaker 11

  Yes.

• 17:35Daniel Whiteson?

  Like, is it an inevitability of like thermodynamics or molecular copying or something? Or is it an evolutionary advantage?

• 17:43Speaker 11

  Well, there, there are two ways of looking at it. One is, you know, the physicist's way would be that, you know, second law wins and there's always increase in entropy and disorder. And eventually things sort of degrade and, you know, life is not a, you know, an equilibrium system. The, the problem with that is that life is not a closed system. And if you apply enough energy and enough resources, you can reverse damage. And in fact, that's what we do. So why is it then that we age and die? Well, I'll tell you the evolutionary argument. The evolutionary argument is, resources are limited.

• 18:26Speaker 11

  And throughout our history, and in fact, until recently, resources were limited for humans as well. You know, we had to struggle to have enough food to live and so on. When resources are limiting, the organism has a choice to make. Does it put more of the resources into maintenance and repair, which requires energy, requires food, et cetera? Or should those resources be put into rapid growth and development? Now, if you take a mouse, for example, a mouse lives about two years, whereas a blue whale lives a few hundred years. So why is it that there's this vast difference?

• 19:10Speaker 11

  Well, the evolutionary argument is that evolution doesn't actually care how long you live. Evolution simply cares about how successful are you going to be at passing on your genes? Because it's selecting for those genes. It's not really selecting for you as an individual. And, and so, in the case of a mouse, there's no point in spending a lot of resources, getting a mouse to live to be forty years. And the reason is that long before that, it'll be eaten, or it'll die of starvation, or in a drought, or of a zillion external causes. And so, in the case of a mouse, it's more advantageous, from an evolutionary point of view,

• 19:55Speaker 11

  for a mouse to grow very rapidly, produce lots of offspring, and then, you know, it doesn't matter whether it dies. Whereas with larger animals, their metabolism is also slower. So they take longer to mature. Their offspring take longer to, you know, produce and grow up and mature. And so, in there, it does make sense for evolution to have selected for a longer lifespan in order to ensure fitness. Okay, because otherwise, it may not actually have the chance to reproduce, or not reproduce enough. And it gets worse than that.

• 20:35Speaker 11

  It's not even that evolution doesn't care what happens to you after you've produced your offspring. Evolution also will select for traits that are advantageous early in life that will get you to maturity and reproduction, even if those exact same traits will cause you to age later in life. And there are many examples of that in my book. For example, certain mechanisms that cause us to age may have evolved as anti-cancer mechanisms. Now, of course, you want to prevent cancer early in life, but later in life, they may cause aging. And ironically, cancer itself increases as we age, the likelihood of getting cancer. But that's a different story.

• 21:20Daniel Whiteson?

  Can you give us an example of an anti-cancer strategy that causes aging later?

• 21:24Speaker 11

  Yeah, sure. So one very classic example is that most of the cells in our body can only divide a certain number of times. And then they reach a state called senescence. Senescent cells are these dysfunctional cells that can't divide, and they actually secrete inflammatory compounds. And as we age, we accumulate more senescent cells, and that becomes a problem, and inflammation becomes a problem. Now, why do cells stop dividing? Well, it turns out that our chromosomes are linear DNA molecules, and their ends are specialized structures called telomeres.

• 22:06Speaker 11

  Now, the copying mechanism for DNA, every time a cell divides, the DNA has to be copied. The copying mechanism is such that our chromosomes get slightly shorter every time the cell divides, okay? And these ends have a special structure. Now, when they become too short, that structure unravels. When it unravels, the end of our chromosomes looks to the cell like a broken piece of DNA.

• 22:36Speaker 11

  Now, the cell has evolved mechanisms that if there's a DNA break, it will either try to repair it, or if it can't repair it, it will send the cell into senescence. Why? Because a cell with a defective genome is at cancer risk because it's got, you know, it could do all kinds of abnormal things. And it's much better to send that cell off to senescence and have it be removed by the immune system than have it continue with a DNA defect or a chromosome defect. Right? So the cell has evolved as DNA response, damage response in order to get rid of cells

• 23:20Speaker 11

  that are problematic in this way. But of course, that same thing is causing senescence and increase in senescent cells as we get older and causing us to age. So that's a very, you know, clear example of how something that may have evolved as an anticancer mechanism early in life really is a cause of aging later in life.

• 23:46Daniel Whiteson?

  All right, I want to hear a lot more about that. But first, we have to take a break.

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• 26:28Speaker 13

  Okay, we're back and we're talking about aging.

• 26:32Kelly Weinersmith?

  So you mentioned that as cells go on and replicate, the telomeres, you know, get shorter, but we, and this is another listener question, but we're able to, you know, combine our gametes with somebody else and make a fetus that has all new cells. And you also mentioned that starfish can, you know, regenerate an entire arm using stem cells.

• 26:51Speaker 11

  Yeah.

• 26:51Kelly Weinersmith?

  So why, why is it inevitable that our cells will break down when we seem able to set the clock back if we want to?

• 26:58Speaker 11

  So we have evolved so that most of our cells have lost that ability to regenerate.

• 27:05Speaker 11

  Probably because you don't want all of the trillions of cells in our body to be able to keep dividing at will, because that is also a cancer risk. Okay, because they could acquire mutation and then they could become cancerous. So we have specialized cells called stem cells, which can keep regenerating. They don't, they don't go into senescence. And they're, these specialized cells, their role is to regenerate tissue. Now, where do these stem cells come from? Well, they came from the fertilized egg. The fertilized egg is the ultimate stem cell, because it's what is called a totipotent

• 27:50Speaker 11

  stem cell. That means it can make everything in the body, including the placenta. Okay? Then that separates off into placental cells and the cells that actually form the fetus and the body, you know, and the organism. Early in development, those cells are called pluripotent, because they can make any kind of tissue. They could make kidneys, they can make lungs, they could make brain cells, they can make anything. But as the fetus, as the embryo, I should say, develops, the stem cells become more and more specialized. And then you have hematopoietic stem cells, which can make anything in the blood system. And that includes all of our immune system and our red blood cells, et cetera.

• 28:35Speaker 11

  Another kind can make anything in the nervous system, you know, neurons, glia, all of those cells. Others can make skin and hair and so on. So 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 the tissue, more of the tissue. So, 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.

• 29:15Speaker 11

  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. You 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.

• 30:00Speaker 11

  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. They're both zero, right? Born at time zero. So that's a combination of two things. One is our germ line 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.

• 30:43Speaker 11

  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? So that's because there's a lot of selection in the process of going from the germ line'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, there, you know, I don't know how many, I hate to guess and take a guess,

• 31:28Speaker 11

  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, for, for health. And then after the fertilized egg is formed, you know,

• 31:50Speaker 11

  It is also checked. So if the developing embryo is at all defective, there'll be spontaneous abortion. Often a woman won't even know it, you know, they're 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,

• 32:27Speaker 11

  you know, the child that is born is, has its aging clock somewhat reset, okay, at each generation.

• 32:38Daniel Whiteson?

  But is it technically possible for us to reset our own clock? Is it just like a bad idea evolutionarily? Or is there something that prevents us from just like constantly being at T equals zero?

• 32:49Speaker 11

  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, okay? And the first time that was done was by John Girdon, 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.

• 33:29Speaker 11

  And 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.

• 33:45Speaker 11

  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 an fully grown adult cell, which was already kind of old and damaged and didn't go, you know, 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. And 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.

• 34:23Speaker 11

  And so that means that you could actually, you know, reset the clock to substantial degree by erasing all the marks on the DNA. Okay? It's not perfect because the cloning itself involved lots of selection. You know, 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 Gert did with this frog? Because they just treated it in various ways, but they didn't have a clear idea of what

• 35:07Speaker 11

  was, what was, 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? 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, 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.

• 35:50Speaker 11

  And introduce them into a 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. Now, 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 in diabetics so that they can produce insulin. There are all kinds of things being talked about and they're, 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

• 36:34Speaker 11

  stimulating new hair growth, okay? And that would be a billion dollar industry.

• 36:39Daniel Whiteson?

  Yeah, if you could develop some like gun, you pointed a part of your body and you're like, make this younger.

• 36:43Speaker 11

  Exactly. So, so people asked, now, the problem with going all the way back is that you have the risk of cancer, you know, because it's, 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

• 37:27Speaker 11

  transiently, you know, just turn them on and then figure out a way to turn them off after a while, then 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

• 38:10Speaker 11

  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. You have to make sure it's safe. You have to make sure it goes to the tissues and just the right amounts. These are all big, challenging problems. And, you know, of course, the 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.

• 38:43Kelly Weinersmith?

  Mm hmm.

• 38:44Speaker 11

  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.

• 39:03Kelly Weinersmith?

  So you've mentioned that one of the reasons that we age and die is because it has something to do with resources and...

• 39:10Speaker 11

  With evolutionary choice, basically.

• 39:13Kelly Weinersmith?

  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, you know, 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?

• 39:40Speaker 11

  Well, somebody did a calculation, a demographer named Jay Olschansky 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 if 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.

• 40:24Speaker 11

  The suggestion is you'd only gain about 15 years of lifespan if you eliminated all of these four causes. And 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.

• 41:08Speaker 11

  Not everybody dies of cancer. Not everybody has heart disease. And also, young people get cancer. So 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...

• 41:54Speaker 11

  Loss of, you know, various functions and so on. And, and then they could use that as the measure of success of their drug. So there, there are ways to get around it. But I, 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. Okay. And that bet was made some time ago and they bet it so that in 150 years, you know,

• 42:38Speaker 11

  the amount would be worth, I don't know, a billion dollars or something. Of course, you know, maybe, maybe it'll cost a billion dollars to buy a sandwich, but by that time, but anyway, but they made this bet. Now 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, you know, there is a, a drug called rapamycin, which is somewhat, it's related to caloric restriction, which also allows animals to live longer.

• 43:22Speaker 11

  That, for example, can increase lifespan in, in mice by, you know, 20 or 30%. Well, if we live, you know, 90 years, you know, 30% of that would already get us to 120 or so, you see. So maybe he's counting on, on things like that. I, I tend to be on the Olshansky side. I, I think that really fundamentally increasing lifespan and especially healthy lifespan is not going to be as easy as they say, because it's, it's highly multifactorial. There are so many things going on.

• 44:00Daniel Whiteson?

  Well, how do we know you're not just a shell for big death? You know, you're being paid by the death industry.

• 44:08Kelly Weinersmith?

  All right, we'll take a break and when we get back, we'll talk more about aging.

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• 46:58Kelly Weinersmith?

  And 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."

• 47:11Speaker 11

  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.

• 47:53Daniel Whiteson?

  So it's got a lot more wisdom, but like, less energy and effectiveness?

• 47:56Speaker 11

  Yeah, and actually, it doesn't function as well. For example, it responds in an aberrant way. It's not as well-regulated. You know, 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

• 48:40Speaker 11

  wrong here. Come 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 know, you get this essentially this explosion in the growth of some senescent cells and inflammation.

• 49:13Daniel Whiteson?

  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 small number of years?

• 49:26Speaker 11

  That's simply the fact that this allocation of repair to maintenance and repair to 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. You know, 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.

• 50:10Daniel Whiteson?

  Because they live longer, so they need more repairs?

• 50:13Speaker 11

  Yeah, and they have to, 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, 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.

• 50:55Kelly Weinersmith?

  This 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 a while and we don't see it often?

• 51:06Speaker 11

  It is almost entirely that we don't observe them long enough.

• 51:10Kelly Weinersmith?

  Okay.

• 51:11Speaker 11

  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.

• 51:24Kelly Weinersmith?

  Oh, that's a cool thought.

• 51:26Speaker 11

  Right, but anyway.

• 51:27Daniel Whiteson?

  Let's have them on the podcast.

• 51:30Speaker 11

  Exactly. So, you know, if they could talk, they might be able to tell you quite a bit. But anyway.

• 51:36Kelly Weinersmith?

  Yeah.

• 51:36Speaker 11

  Now, it was thought for a while that these things, 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 is, you know, old, you know, they have all these.

• 51:53Daniel Whiteson?

  They don't know how to use the VCR.

• 51:55Speaker 11

  Exactly. They have all of the same problems and it's just that it happens more slowly.

• 52:00Kelly Weinersmith?

  Okay. And I gotta say, Daniel, I think the VCR joke aged you more than anything.

• 52:06Daniel Whiteson?

  Well, the fact that you laughed at it aged you.

• 52:08Kelly Weinersmith?

  You got me. That's true. That's true. So let's jump back, if that's okay, to another example of folks trying to extend lifespan. So 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?

• 52:31Speaker 11

  That's, that's an excellent question. And it is true that when they connected an old rat to a young rat.

• 52:40Speaker 11

  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. So 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, but there was some effect both ways.

• 53:26Speaker 11

  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-

• 53:38Daniel Whiteson?

  Where do I buy babies, this kind of stuff?

• 53:40Speaker 11

  Exactly.

• 53:42Speaker 11

  And in fact, companies sprouted up. And as you can imagine, mostly in California, I think.

• 53:51Kelly Weinersmith?

  That's what I would have guessed.

• 53:52Daniel Whiteson?

  You mean the center of innovation and forward thinking and creativity? That's why you said California.

• 53:59Speaker 11

  Anyway, somehow obsessed with youth.

• 54:05Speaker 11

  But anyway, some of these companies would 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 one, 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?

• 54:29Kelly Weinersmith?

  Oh, my goodness.

• 54:32Speaker 11

  It was really bizarre coming from, you know, a CEO of a, you know, a health-based company.

• 54:40Daniel Whiteson?

  But you're saying that there are real benefits to having transfusions of blood from young people?

• 54:44Speaker 11

  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, you know, top scientists from very well-known universities are actually working on that. But, you know,

• 55:26Speaker 11

  this idea that you should just take transfusions, you know, 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?

• 56:06Daniel Whiteson?

  Well, the thing that fascinates me about Brian Johnson is that he does take a lot of data, right? He is focused on these metrics, right?

• 56:14Speaker 11

  He's focused on metrics.

• 56:15Daniel Whiteson?

  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...

• 56:25Speaker 11

  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, 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 on online. He's a cellist. So.

• 56:47Daniel Whiteson?

  Well, you're definitely biased, but I don't I don't not believe you. But, you know, 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 know, you're measuring the damage to whatever molecular mechanisms, but still somehow not be young in in the sort of social sense.

• 57:07Speaker 11

  That's a that's a very good question, you know. So, you know, I mentioned the high school reunion and how we all look different.

• 57:13Daniel Whiteson?

  Yeah.

• 57:14Speaker 11

  So that's led to this quest for biological markers of age. Okay.

• 57:20Daniel Whiteson?

  Yeah.

• 57:21Speaker 11

  Because you want to know, you know, your birthday may have been, you know, forty years ago, but how old are you really in biological terms, right? So 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. Okay, happens even in utero. We're aging even in utero. Okay. And that's apparently better correlated with with mortality than chronological age, you know. So the chances that you're going to die are more correlated with your DNA methylation than they are with your date of birth. So so that's, you know, used as a clock.

• 58:05Daniel Whiteson?

  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?

• 58:12Speaker 11

  That'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. This is called glycation. And so you can measure this, you know, 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, you know, decay of the immune system. But anyway, that's another clock. Now, people will sell you kits. They'll sell you a DNA methylation kit or a glycation kit or or or full blood, you know,

• 58:57Speaker 11

  library, you know, they'll just analyze a bunch of stuff in your blood to give you a sort of biological age. And each one will say this is our our thing is the most accurate. Okay. 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? Okay? That'll give you a good idea of, you know, 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.

• 59:39Daniel Whiteson?

  Yeah.

• 59:40Speaker 11

  Okay? I think they need to agree on a panel and then say, 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. So, so I think people need to have a more complex view of aging, of biological age.

• 1:00:11Daniel Whiteson?

  But don't we also need to unravel this question of causality? I mean, if you identify a marker even 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 and 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?

• 1:00:55Speaker 11

  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, that 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. So if you're going back to an earlier state, you maybe you're you're going back to an earlier program. But I I agree that, you know, causality, you know, needs to be established by

• 1:01:41Speaker 11

  careful experiments, you know. Is is it sufficient to reverse methylation? And would that cause 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.

• 1:01:58Kelly Weinersmith?

  So I imagine our listener is 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?

• 1:02:11Speaker 11

  Yeah. Yeah, I I should say, you know, I there's no theoretical reason why we couldn't all start living to be 150 eventually. Okay. The 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.

• 1:02:54Speaker 11

  We're really interested in extending health span. Okay. And 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 of 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?

• 1:03:38Speaker 11

  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. Okay. So it's just postponed. And in fact, you know, we're living more years in a 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.

• 1:04:17Speaker 11

  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. The one exception to this are supercentenarians. 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 a hundred or so. And then they suddenly go into a decline and die. Now, you could ask, why is that?

• 1:05:03Speaker 11

  Well, it could be that they're selected and they're just, there's a selection bias there. First of all, they may be lucky in the combination of genes that they have. But they, 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. And you're looking at the survivors, okay? And so this, 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.

• 1:05:49Speaker 11

  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. In other words, you're not losing weight and starving, but you're just steady.

• 1:06:30Speaker 11

  But that's, that will leave you hungry and cold and loss of libido and all sorts of side effects, which maybe not. Not worth it. Not worth it, yeah. Reminds me of that joke about the doctor who said, you know, if you do these things, you'll live, live longer. And the patient said, really? He said, well, I'm not sure, but it'll feel like it.

• 1:06:54Speaker 11

  So anyway, so but but you could have a moderate diet, you know, and 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. So, 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?

• 1:07:36Speaker 11

  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, etc. 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. So that trio is extremely healthful. 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.

• 1:08:20Speaker 11

  So there's, it's like a three-legged stool that help, you know, each one helps the other two.

• 1:08:26Daniel Whiteson?

  But then let me ask you about that specifically, because it feels like as we get older, it's harder to sleep longer, 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.

• 1:08:38Speaker 11

  Exactly, and that's why if you exercise and eat well, you're more likely to sleep well. And and then it's a it's a kind of virtuous cycle, they help each other, each 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

• 1:09:20Speaker 11

  to live longer. And 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 that some people would argue that's a purpose too. So, 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, maybe more inclined to do these things. So there is this correlation causation issue, but I think it's it's well worth considering.

• 1:09:59Kelly Weinersmith?

  Is it time for the alien question, Daniel?

• 1:10:01Daniel Whiteson?

  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. And so since we're in this moment where we, you know, maybe on the cusp of discovering aliens on the other planets in the next decade or whatever, do you think that?

• 1:10:20Speaker 11

  I'm very agnostic about that, by the way.

• 1:10:22Daniel Whiteson?

  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?

• 1:10:37Speaker 11

  I think so, because I think natural selection is a 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. So 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, you know, it's more likely even to have that. And ultimately, ultimately, the laws of physics, which, you know, Result in chemistry, which results in damage.

• 1:11:20Speaker 11

  That's not going to change, you know, somewhere else.

• 1:11:25Daniel Whiteson?

  So everywhere across the galaxy, there are grumpy old aliens telling those young kids to get off their lawn?

• 1:11:32Speaker 11

  That, that, that, that, I would, I would bet on that if I had to, but, but I'm, I'm, I'm somewhat skeptical about. I think we don't know what the probability of life here is.

• 1:11:43Daniel Whiteson?

  Yeah.

• 1:11:44Speaker 11

  And until we know that, we have no idea whether life elsewhere is, is very likely, or whether we're alone, or somewhere in between, we, we, we 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, you know, there are people who feel

• 1:12:08Daniel Whiteson?

  Right.

• 1:12:08Speaker 11

  that we may be the only intelligent species and we should go off and colonize not just Mars, which you guys pointed out is extremely hard anyway. But, but, but, you know, even other galaxies. And, 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 which seems like a crazy idea, but anyway, that's, that's how it is.

• 1:12:35Kelly Weinersmith?

  I think for a lot of people, it's like, you know, they'll say, oh, I want humanity to do it. But what they mean is that I want to be the one who does it in particular.

• 1:12:42Speaker 11

  And so. Oh, yeah, yeah, yeah. No, absolutely.

• 1:12:45Kelly Weinersmith?

  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.

• 1:12:52Speaker 11

  Thank you. It's been a real pleasure chatting with both of you. And by the way, I really enjoyed your book.

• 1:12:57Kelly Weinersmith?

  Oh, thanks. I loved your book.

• 1:13:05Kelly Weinersmith?

  Daniel and Kelly's Extraordinary Universe is produced by iHeartRadio. We would love to hear from you.

• 1:13:11Daniel Whiteson?

  We really would. We want to know what questions you have about this extraordinary universe.

• 1:13:17Kelly Weinersmith?

  We want to know your thoughts on recent shows, suggestions for future shows. If you contact us, we will get back to you.

• 1:13:23Daniel Whiteson?

  We really mean it. We answer every message. Email us at questions at danielandkelly.org.

• 1:13:30Kelly Weinersmith?

  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 and K Universe.

• 1:13:39Daniel Whiteson?

  Don't be shy. Write to us.

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