Do We Have To Die? With Venki Ramakrishnan

When we talk about death, it's a little complicated because there are many different kinds of death. Oh, you can have societies dying, cities dying, companies dying. But what we're talking about is the death of the individual.

There's a peculiar paradox there because while you're alive, I mean right now millions of cells and you're dying. You don't even notice that. That's cell death. You start aging even in uterero from the time you're conceived. you know, your fertilized egg starts developing. Is that why all children are born looking like old men?

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This is Star Talk. Neil deGrasse Tyson, your personal astrophysicist. This is special edition, which means we've got Gary O'Reilly. Gary. Hi, Neil. Hey. And we got Chuck Nice. Hey. Hey. Hey. Okay. What's happening? uh as special edition specializes in all science that matters to the human condition. Yes. And today's topic is no exception. No. And I I may I give the title of it. Please do. Why we die?

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Why we die. Well, I have no expertise in that other than simply being alive, right? I I fear death because I'm born knowing only life. Wow, look at that. Yeah, I got that from a movie. Oh, okay. That's okay. So, Lane and I are co-producer on this. Lane, our LA producer for Star Talk. Yes. We have long wanted to investigate this subject matter. You want to investigate it, but not firsthand. No, no, you want firstand data. More an observation, right? More an observation. So if you put it this way, humankind has for millennia asked, "Why do we die?" followed by, "Well, why can't we live forever then?" And then it's kind of the same question. Yeah. But you know, aren't different people. So has evolution programmed us to expire on a certain date? Could we extend the game, cheat death, play God if you wish? Millions, if not billions, are spent annually on anti-aging, be it research or products. Millions of dollars. Yes. And so how close are we to unlocking the mystery of death? So no surprise that the research into proteins is proving to be the key to this mystery. So the building blocks of life may hold the key to death. How about that? Wow. Oh good sentence there. Very good Chuck. So we have the world's expert on this very subject. Wow. And this is Veni Rama Krishnan. Veni. Welcome to Stark Talk. Thank you. Excellent. And you are now based in Cambridge. Yes. England. Say it. I knew I knew you. Wasn't really necessary. It's always basher Brit day here. Yeah. Yeah, it is. It is. But we do it lovably. We do. Yeah. Uh, so you run a small group, but used to be bigger because you're winding down. Yes. In your career, a program leader at the MRC. That stands for Medical Research Council Lab at Cambridge. Yes. And it specializes in bio molecular biology. Molecular biology. So it's the MRC lab of molecular biology. Okay. Okay. Our name is what we do. But that's like the least of your resume here. So in 2009 you were awarded the chemistry Nobel Prize. Wow. Why are you wearing it under your shirt right now? No. Cuz that's serious blank, you know. Honestly, you go to the club. Yeah. I would be like the flavor flave of Nobel Prize winner. I would never take it off. So, uh, former president of the Royal Society. Very important. That's a deal. Organization that basically the first, we think the first in the world to organize the ideas and publications of scientists. Wow. To make it a clearing house of peerreview, first peer-reviewed papers. also advocated evidence-based science uh in the 17th century at a time when authority mattered a lot and they said authority doesn't matter beauty doesn't matter it's evidence that matters very enlightened and important posture and then you got kned in 2012 that's three years later and you do they knight with an actual sword yes but it's I think it's blunt Well, let's let's just hope you don't want me to slip up if there's a little sort of jiggle in the wrist. We wanted to make him a knight. It turned into an execution. So, who was on the other end of the sword? Yes. Uh, it was um Princess Anne. Oh, cool. Cool. All right. We love that work. Yeah. Yeah. Oh, also you have a book um it's your second book, first one a few years back, The Gene Machine. But what we're especially interested in now is Why We Die. And uh give me the the subtitle of that book, Why We Die. It's called The New Science of Aging and the Quest for Immortality. Well, let's dive right in because you are our world's expert in this. And before we can define death, I guess we should kind of define life and then learn what it is that ceases in life that then brings death upon it.

Well, defining life is is very hard. It's, you know, you could almost say quote Justice Potter Stewart as I can't define it, but I know when I see it speak spoken of maybe you don't know pornography because that's America that he said that of pornography. Okay. But the fact is um life most biologists would define it as a system that can self-replicate and evolve. And at least in our world, it's carbon-based.

But when we talk about death, it's a little complicated because there are many different kinds of death. Oh, you can have societies dying, cities dying, nations dying, um you you can have companies dying. But what we're talking about is the death of the individual which has a the organism of an individual animal or organism, right? And there's a peculiar paradox there because while you're alive, I mean, right now, millions of cells in your dying, you don't even notice that. Okay, that's cell death. Why you got to tell me that right now? No, cuz it's fact. They need to die in order to in order to keep you alive. Oh my goodness. That's how he got out of that. Thank you. Dead cells. So to make room for the new cells to make new room for the new cells. Actually during development cells will die at precise points as during development. They've done their bit and then they have to get out of the way. When you say development mean embryionic. Embryionic development. Correct. And at the same time when you die when you say a person has died at the point of death most of you is still alive. That's why you can donate organs. Right. Okay. So there's there's the other side of the paradox. Interesting. So what do we mean by death? Okay, you're going to have by the way since you're an astrophysicist, you're going to have death of the universe as well. And there's a book coming out on that or has come out. So the question is what do we mean when an individual dies? What we mean is the irreversible loss of that individual's ability to function as a coherent whole. M so that means that person can no longer exist as a as a unit and that's what we mean by death.

Are are you talking physiologically this person cannot function as a unit because there are people who experience brain death or an to an extent and they keep them on a respirator because a family member says I don't want them to die. So there are two examples coming out of Chuck's point. You can be brain dead but sustained on a respirator. So all your organs are working and or you can be body dead I suppose and in the limit it's like your brain in a jar or whatever. No that's well no that's more can happen but that's more like a quadripeic that can't what you said can't happen because if your body is dead then it can't feed nutrients to the brain to keep it alive. The brain is the biggest consumer of resources resources in in so uh coming back to your point though about brain death etc. That's interesting because it used to be that if your heart stopped beating, that was the moment people said you're dead. Then they found out that actually even if your heart stops beating, they can resuscitate you, right? But then they decided, okay, when you no longer have brain waves and your brain has irreversibly stopped, uh, that's brain death. And there's an interesting case, states in in the US used to have different definitions of death. And there was a case where somebody died in California but her relatives wouldn't accept it and by New Jersey laws she was not dead. So they moved the body to New Jersey. Oh wow. And she was maintained as you say on some sort of uh artificial device and then eventually uh she died. But this is slightly getting semantic because most people agree that there's a point when the body cannot reverse itself and get back to being alive. Yeah. But that's a statement of the limits of medicine in the day today. Right. So I remember I mean I read this that one of the definitions of death is if you do not fog a mirror held up to your mouth. Yeah. And I'm thinking that's respiratory. Yeah. That was a long time. I'm thinking You know, I'm glad that's not when I'm alive. I mean, I'm just thinking, thank you for Right. Thanks for not being alive at back then cuz I'm a light sleeper. Okay. So, that tells me that however real our current definitions feel about when someone dies could be modified in the near or distant future. Absolutely. And and neither birth nor death are very clearly defined. And I've pointed this out that they're both somewhat fuzzy. I mean when when is it that you actually are you at at birth and that's the whole argument about about abortion and all of that is just about that and similarly uh the point of death is also when are you fuzzy you yeah that's that's wild yeah so the bit in between is aging the bit in between is aging and unfortunately for us the little bit in between I may have downplayed that there and in fact you start aging even in uterero Bro, interesting. From from the time you're conceived, you know, your fertilized egg starts developing. Is that why all children are born looking like old men? Winston Churchill. So that's even earlier than a loaf of bread cuz you know when a loaf of bread starts aging. No. Right when you take it out of the oven. Yes. Exactly. Okay. In that moment it starts getting old. Right. Right. But here this is in the oven. In the oven you're getting old. Okay.

Forgive me as an astrophysicist. I hear talk of cells and and but then I also hear talk of proteins. So could you distinguish the two of them for me with regard to the role of aging? So aging is you can think of aging as an accumulation of damage and changes to our molecules, our cells, our tissue and entire organs and the body. And this aging occurs at every one of those levels. So if you think of the molecule that holds all the information necessary to make all of the other molecules in the cell, that's our genes, our DNA. So DNA can be damaged. It can also change, which is not exactly damaged, but it can be modified as we age. Uh typically by adding chemical groups to it, often methyl groups is gene editing. It's uh it's epigenetics. It's not editing as such. It's not changing the bases. It's not changing the letters of the uh DNA. That would be gene editing. That would be gene editing. This is epigenetics, which means sort of on top of of genetics, like the epicenter of a earthquake is the point on our surface above where the Right. Yeah. And so you can you can modify DNA and that changes the way in which the program is expressed. So which genes are are are translated into protein? So this is the playing God part because now you are changing the No, we we're not doing anything. This is happening. This is happening in experiential um circumstances can change your epigenetics. Part of control of it's just part of life and it evolved for probably a very good reason. uh mainly it may have been of a cancer prevention mechanism early in life. We can get into why we have death from an evolutionary point of view. But nevertheless, uh the DNA program itself ages you know damage and modifications change the nature of the genes that you're expressing then uh that results in the proteins which are encoded by DNA. There you go. These are the workh horses of the cell. They carry out all the function. They give out they give the cell its structure. Almost everything you think of as a property of life like vision or touch or uh you know or or antibodies, they're all proteins and they're all encoded by DNA. But as we get older, the quality of the proteins deteriorates. They're not made at the right time and the right amount. They start aggregating. that you know Alzheimer's is a case where proteins clump up together and form tangles. So that also yeah in the brain so that also uh is a consequence of age and as a result things in the cell larger entities like compartments in the cell uh also start to age. One of them are mitochondria which are mitochondria were actually bacteria that were swallowed up by a larger cell two billion years ago and then lived in symbiosis and uh now today mitochondria are specialized as the centers for energy metabolism. It's where oxygen is used to to burn sugar effectively and get energy out of it. So, it's that kind of chemistry going that far back that accounts for our genetic similarity to life forms that are nothing like us. Like the, you know, we're something like 25% identical genes to a banana. Yes. Yes. All ukariots came out of that. Yes. Out of that symbiosis. Okay. And so so you can think of this as an ancient, you know, organal that's now specialized. And because it's a center for oxygen usage, it can create what are called free radicals or reactive oxygen species because these are partially reduced oxygen atoms which are chemically very reactive. So there's you can have a lot of damage. To be clear, if it's fully reduced, that means all the oxygen is where it becomes water and then you can't there's nothing else that can carbon dioxide and water is where you get Yes. It's fully reduced partially. It's it's basically activated. It's activated to do things and it does damage. Yeah. Yeah. And so it can cause damage. And mitochondria have preserved a little bit of their own genome. They used to have a much larger genome when they were bacteria, but now that genome has shrunk in in humans. They only encode 13 uh protein genes, but they're essential for the function of mitochondria. And the mechanism to replicate that DNA, to copy that DNA as mitochondria divide, it's not as accurate as as the mechanism for our own DNA replication. The more errors creep in and so mitochondrial aging is a big problem with our aging. Is that the single point of failure in terms of the It's not a single point there. I think aging, you know, mitochondria. Yeah. Some of my lifelines like aging is like a cascade failure. But I I do like to say that the reason my grandson has a lot more energy than I do is because he has much better mitochondria than I do. Something's going on with the mitochondria for your skin because your skin's perfect. I don't know how old you are, but you know, clearly I look at your hair and I'm like, "Okay, this guy's old." But uh but I look at your skin. I'm like uh but he stole his skin off of a teenager. I thought black don't crack. That's true. Black don't crack. And that you're absolutely right. It doesn't make a difference. It's the dark skin. It's the dark skin. Yeah. It's just melanin. Yeah. That's just melanin. At the end of the day, so this reduced chemistry that makes it chemically active that could not have been useful before Earth's atmosphere became oxygenrich. That's right. So we had So that and that happened because of the cyano. What? Yeah. [Laughter] So cyanobacteria basically turned a carbon dioxide atmosphere into one that had a presence of oxygen. And then anything that needs oxygen can thrive can now thrive, but it couldn't before then. So So that helps age date or time date I should say. It's about two billion years. That helps time date these activities. Yeah. That's the watershed moment for very good waterershed. I like that. That was good.

So there's something called scinsesscent cells where where they age and they secrete these sort of inflammatory compounds. So scesscent cells are another I mean I said you can have aging at every level and aging at this at a cellular level is often due to scinessence and scinessence is interesting. It may have evolved originally as a anti-cancer mechanism or as a mechanism to get rid of defective cells. Yeah. So what happens is if a cell gets DNA damage it has a number of enzymes to repair the damage to sense and repair the damage. But if the damage is too extensive then it triggers pathways to either kill the cell commit suicide or to send it into this state called scinessence. Yeah, that can also happen, you know, due to other kinds of stresses. And what scinsesscent cells do is they no longer function normally and they no longer divide, but they secrete inflammatory compounds. And the purpose is to signal to the immune system that there's something wrong here. Come and repair the damage around this site. Maybe it's a wound or infection or something. They call the cavalry and Exactly. Call the cavalry. So it has utility. It has it has utility early in life until it doesn't but later in life you get too many of these events buildup of scinesscent cells systemic inflammation which causes organ damage more scinsessence and so it's a big problem in aging. Wow. Yeah. And that's why you see so many medical reports now that talk about the dangers of inflammation. Absolutely. Totally. Like it doesn't make a difference what kind of inflammation. The idea is to eliminate inflammation as much as you can no matter what. Sure. And actually people know for example in the COVID pandemic uh the the cause of death is often triggered by inflammation right not by necessarily directly by the virus by the virus itself. So it's a reaction. So it's the the cytoine storm that was created as a reaction to the virus itself. Cytoine. Cytoine. Please explain. Cytoines are if I'm not mistaken or he can get him to answer. Oh, can you answer that? Yeah, because I'm not an uh but yeah, it's the cytoines are what's released when we respond to what our body thinks is an attack on us and u sometimes you can it goes in overdrive. It goes in overdrive and yeah.

Are we anywhere close to being a or is this the epigenetics thing where we can deal with these scinesscent cells? No. But there is a new field emerging which is cellular reprogramming. Oo yeah that sounds sexy. to to explain that. If you start from a single fertilized egg, it divides into uh many cells, becomes uh something called a blastula and then or a blastoyst and then you it divides further and further and then forms specialized stem cells and each of those specialized stem cells give rise to certain kinds of tissues. Yes. Right. Okay. So some stem cells will only generate cells of the uh blood system including white blood cells, red blood cells and so on. That used to be thought of as unidirectional. You go you can't go backwards. You can't go back from a skin cell back to a fertilized egg or early embryo. But that turned out not to be true. Okay. And I actually it was done in a natural way when Dolly the sheep was cloned. But actually even earlier when John Girden cloned the skin cell of a frog uh and cloned an entirely new uh animal from it. Wow. And and that meant that somehow these marks on the DNA had been erased and or changed just historically that completely changed the public dialogue about our source of stem cells, right? because we we only were getting them from aborting blood. Yeah. From fetuses. From fetuses. And so that was a complicated ethical issue for many people, right? And then once this that blew open that whole, right? Well, that wasn't Gordon and Dali the sheep and others, but it was actually uh Shina Yamamura a Japanese scientist who showed that if you were to introduce just four factors, these are genes for proteins that regulate other genes. Gotcha. If you were able to introduce those four factors, you could take a fully differentiated cell like a skin cell or liver cell or heart cell and you could make it go backwards in development all the way back to what's called a plur potent stem cell. Pluropotent means it can make any tissue, right? And so that eliminated the need for what you said. Did he not win a Nobel for that as well? He did. He and John Girden shared a Nobel Prize. Here's an interesting thing. John Girdton's paper for which he won the Nobel Prize was published the year Shinya Yamamura was born. No, that's how that's how far apart they are in. And all that time, all that work and then he just comes along and takes credit for it. Look at that. Look at that. We've had we had sort of variations of this with David Sinclair who had a guest as a guest took mice that were blind. Correct. It sounds like a nursery rhyme. Three of them. Don't start. You did it, didn't you? Godamn. You couldn't have to go there. You did. And turn them into sight. Cured their blindness. Yeah. So, I mean, we are I mean, if that's the case, how far are we from I I would say it's early days. Okay. I can tell you that I'm aware that this has happened. But then my question is just the distance between this and doing other things on a grander scale. Mice are one thing. larger primates. Yeah. And and and curing blindness. It's a little further down the line is what you're saying. It's a little but the idea is we do have would you say we h we now have a not a blue print but maybe a template that we know we can take these programming cells and use them to maybe change our makeup. I think the biggest use of that is in something called regenerative medicine where if you want to replace tissue that normally can't be replaced for example damaged heart muscle in and an heart attack or uh pancreatic tissue which has been destroyed and you have diabetes or cartilage for example for osteoarthritis. Absolutely. And maybe one day uh I'm hoping even hair. So, so if you can, it looks good on you though. Very few people can pull this off. Anyway, so if you can do that, that regenerative medicine is a is a huge area of research. Yeah. And they're making good progress in in some things. Just to be clear, I've always been disappointed in humans for not being able to regenerate limbs the way NES do. Exactly. That's because NES have stem cells all over all over their body. all over the whole spread out throughout and so they can or starfish for example we're old enough to remember reading biology books humans are the top of the evolution everything back when we spoke that way unless you lose an arm unless you went through the list of all the other animals that do things way better than we do and I quickly re re it's not a short list it's humbling to know that we have about the same number of genes as a worm or a weed Right. So yeah, there you go. Put us in our place. Yeah. Anyway, u but going back to stem cells, the thing with aging is can you take a fully grown or an aged individual, apply these kinds of factors and get their tissues or their stem cells to be regenerated, right? Because one problem with aging is that our stem cells also age. They decline in number and in quality. So if you were able to take use a method that would somehow either reu rejuvenate tissue or actually regenerate stem cells that would be a big thing and people have done experiments to do this kind of thing in mice and they say that the mice I mean the papers report that the mice look healthier uh they they seem younger by many criteria and so on but how to do this safely and the bald mice did they get hair back? No, but their fur looked better. Oh, okay. Okay, that's not bad. So, so the question is how can you do this in humans in a way that's safe, that doesn't cause cancer, that is at the right dose and so on. And that's a big challenge. So, I I think it's promising, but like many of these things, you know, the aging field, I should say, is full of hype. Okay. And um it's very promising, but there's a lot of work to be done before it's ready for prime time.

We had this sort of Frankenstein moment. I mean, we you've done a Frankenstein show before with the let me get his name right, David Andresovich. You know, the cells will you've said there can be death to the the organism, but cells will remain alive. And now we've got the Yamanaka factors. Are we getting to that thing when we can create or are we just fantasy talking here? You mean create a new individual or the same individual? Well, the same individual. You could certainly clone yourself. That's that's theoretically and practically possible. They've cloned all kinds of mammals. There's no reason why they can't clone a human being. Uh except that all countries have decided that's a a bad thing to do. But that's not the same as as rejuvenating or the same individual. Right. Right. Which by the way, for selfish purposes, rejuvenation is a hell of a lot better than cloning cuz that clone is not me. Exactly. That's people forget that. Yeah. Yeah. And there's all this fantasies of in the multiverse where you have an infinite number of possible molecular outcomes, right? of all organisms, they're imagining themselves in another universe in a way being reincarnated and living forever. It's like, no, that's a different that's just a different person in in a different timeline. And by the way, these transhumanists, you know, people who think that they're going to dump their brain into a computer and then maintain their consciousness, a simple question to ask is, what if you make two copies of it? Which one's the real you? You know, and you immediately have a paradox. Absolutely. That the copies that you make will be of you of that moment, but you've in your timeline are still proceeding. They would be stuck. You still get to the beach and have friends and your your brain in a jar does not. Mhm. Right. Yeah. Oh gosh. Or your brain in the silicon chip, right? Is you from whenever was you created it.

So, so I heard long ago and I checked it out and I think it's true that all mammals live for about the same number of heartbeats except for humans who live two or three times that except if you go back far enough in time when we were just living in caves. We were right with all the rest of the mammals. So, first, is that true? Second, there are animals, not mammals, that live much longer than we do. I'm thinking of the Galopagus tortoise, for example. Yeah. So do you guys study other animals to get insight? So there is a whole field devoted to looking at lifespan of different species and uh you are right that at least among mammals Jeffrey West who's written a book called scale shows that the number of heartbeats is is roughly the same. That has to do with the fact that smaller animals have a higher metabolic rate. They have a faster metabolism and and they almost need to because their surface to volume ratio is larger. They dissipate heat more. We did a whole explainer on surface to volume ratio and so they they they need to maintain a higher metabolic rate. Uh that's one of the reasons. Well, that's only one of the reasons why they have higher heart rate. That's not a reason why they should die sooner. Ah the why we should die die sooner is has an evolutionary explanation and that is evolution doesn't care how long you live. It only cares about fitness. Fitness in the biological sense is the likelihood that you're going to be able to successfully pass on your genes. And people always misinterpret that as being physically fit or stronger or whatever. Survival of the fittest as in I'm in great shape. Yeah. Darwin should have found a different word. He said, "Yeah, so evolution cares about fitness." Now, at the same time, for most of our history and certainly the history of all other species, resources are limiting. And so you have to select, do you put more of your resources into maintenance and repair of the individual animal or do you put it into growth and reproduction? There's always a balance if you if you have limited energy. So, in the case of a mouse, which lives about two years in the wild, uh there's no sense in having a mouse live for 40 years because long before that, it's going to be eaten. Exactly. You beat me to or it'll die of starvation or or drought or something. And so in the case of a mouse, evolution has favored selection of a species that grows very quickly and reproduces prolifically. That's a mouse. If you get to a a large animal like a boowhead whale, let's take a an even even bigger than an elephant. They can live for two 300 years and they have a very relatively slow metabolism. Wow. An even slower metabolism is not a mammal, but it's still a vertebrate called the Greenland shark. 700 years. Listen to that. A vertebrate living for 700 years. Very slow metabolism. Wait, wait, wait, wait. How do you know that? We didn't even have marine biology 700 years ago. So, how they they can do things like carbon dating and they cut one open. It was 700 rings inside. I mean, you've got on the I'm just No, no, no, no. So, you've got the mayfly lives a day. Mayfly lives a day, right? And then between that, you've gone from there to a Greenland shark and your Galapagus. And there other animals that are thought not to even age biologically. What's the immortal like the hydra and the immortal jellyfish? These things are there's an actual animal called the hydra. Yes. Awesome. Not just in in not just in GI Joe. No. Oh, no. Marvel. No, no, no. In in in mythology. Oh, you mean the real hydra? Yes. This is a freshwater small animal. and and they're full of stem cells, so they're constantly regenerating themselves. But if you followed an individual, it would also age only very slowly. It's just in the wild, it it it dies for other reasons before actually aging. So, so there's a whole range. Now, so humans might be the only species that dies of natural causes in the world. I mean, if you want to think about it that way, possibly, you know, we're apex predator. Yeah. So yeah, I think that may be true. In fact, there's a book uh written by Steven Ostad called Methusela Zoo, which where he talks about all these animals and he talks about Methusela Zoo. Love it. It's a it's a great book. So that reminds me because Methusa is the oldest person in the in the Bible, right? In the in the Old Testament Old Testament Bible, the oldest star we know of in our galaxy is called Methusa. It's called Methusela. Yeah. Right. So Methusa had a lot of influence. Yeah. And that star too is lying about its age. Who knew that? Anyway, uh in this book he he points out Methusela Zoo in Methusela Zoo. He points out how all these species have such different lifespans and it's because of this evolutionary selection. But it's actually worse than that. It's the fact is evolution will select for things that help you early in life even if they cause a problem later in life. So many of the things that cause aging are related to growth for example or to cancer prevention, you know, prevention of or the or scinesscent cell creation. These things all help us early in life and they're they're a problem later in life. But evolution doesn't care what happens to you when later making babies. Correct. Exactly. Yeah. Because that's the whole deal. So what helps us survive in infancy and then go on to reproduction is the key component of our decline and demise. Not always. Not everything, but there are things that happen to us early in life that are selected for early in life that cause aging. So, the real deal is just keep having babies your entire life. Uh, and then you you you'll never age. However, you will eventually kill yourself because of these kids. So, so we're we're an outlier. We're an outlier. We live about twice as long twice as we would based on our size. But only post caveman life, right? Um 40,000 years. Exactly. So only I mean half of everyone died by 30 and so we're not 2x other mammals at our size. Right. Yeah. And one last thing is there's a group of animals, mammals, the bats, they live much longer. They're about the same size as a mouse in in terms of mass. Yeah. You mouse. They they they live about 10 or 20 times as long as a mouse. Mhm. And the reason is they can fly around. So that means two things. They can escape predators more easily and they can also forage over a much wider area for food. And and when they roost, they roost in the ceilings of caves. So they're not as accessible to predators. They've been designed to survive longer. And so there it's worth it for evolution to make them live longer because they'll still keep producing more babies. Yeah. So you got to be grandpa monster is basically the deal. That's what grandpa from the monsters. The grandpa from the monsters. If you want to live long, sleep hanging upside down away from predators.

So, if we're looking at aging, we all do it. Can't help it, more or less. What have been the attempts to reverse the aging? I'm not talking potions and lotions here. So, let's go through the laundry list. The sort of young blood transfusion. Oh, yeah. How successful has that been? It's not incredibly successful, but the science un underlying it is solid. If you connect an old rat with a young rat, Yeah. by that I mean you connect them so that their blood systems uh you know sharing the same circulation system. Exactly. Then it turns out that the old animal benefits from the blood of the young animal. Uh but even more so the young animal suffers from the blood of the old animal. Wow. And so this means there are factors in blood that change as we age. And there's such a thing as old blood. Exactly. Or young blood. And that's why I I call it as vamp vampire blood. Yes. So that's the science. And and the research is now about finding out what these factors are, what they do, and once you know that, you might be able to figure out whether you can use them to our benefit. But people have not waited for that. What's happened is the very first time these people from Stanford uh Rando and others published this, they got creepy phone calls from rich people asking you blood and and companies started sprouting up uh getting blood from young donors and extracting the plasma and selling them up, you know, at $8,000 a pint or something to, you know, rich old people. And uh one of them the FDA wanted to shut it down and then they sprouted up under a different name. It's all the whole thing was like the wild west but there's real science under it and and and that's an ongoing area. Okay. Stem cells we've kind of addressed as to how you can through the Yamanaka factors dial up dial down and that's that I would consider that Yamanaka. What is the Yam Yamanaka factor? The Oscar winning where he sort of can Oscar winning. Yes. Oscar winning. He was a bloody good actor. He's an unbelievably good actor. Nobel Prize winner. Thank you. Okay. That guy, right? That guy. Thank you. Okay. The Nobel Prize is straight here. Okay. The calorific restrict or caloric restriction. Yeah. So, basically fasting. It is. It is. So, lots of experiments starting in mice, but now also in flies, worms, even in single-sellled animals like yeast. If you reduce the amount of calories, it turns out that you can the the animals live longer. But more importantly, older animals start resembling younger animals in terms of their physiology and their biomarkers. And so the question is, can you mimic caloric restriction? And it turns out that there are many important biochemical pathways that are affected by caloric restriction. One of them is uh the IGF-1, insulin growth hormone factor. So, but just to be clear, what you're saying, you wouldn't have to imitate calorie reduction. You could just consume fewer calories. So, so what you're trying to do is we can still eat our cheeseburgers and the blueberry pie dessert and then you hijack what would be the the starvation mechanism biochemically. Exactly. That's intermittent fasting. Yeah, but I don't have to fast. Is this the GOP world? Oh, yeah. The whole point is not to fast just to restrict you. No, no, no, no. Did you get what I just said? No. What he's saying? That's why I paused on it. Have your cake and eat it. You have your cake and eat it. Yeah. Yes. But explain your your point again because I missed it. Okay. So, the point is what he said. He just slipped it in, right? But but I caught him. Okay. He's saying fasting fasting will prolong your life. Absolutely. So, can we find a way to mimic the biochemistry of that in your body? We can. And the word mimic in that sentence means still eat the cheeseburger and but do what the fasting would have done to your biochemistry. I see. Yes. Have your cake and eat, but you're doing it artificially is what you're saying. I in my book I call it eating your blueberry pie and ice cream and and getting the benefits of and still getting the benefits. So, have we done this? No. Well, there are there are some drones. Okay. No, no. I'm I'm not working on it. But I should say I'm out this game. I should say it was like, did you see the way he just went like this? No, no, no. Not me. They keep trying to keep me working. I'm telling you right now, I'm out. But if you do know how to do it, tell Chuck cuz he'll set up a company. Lots of companies. That's a problem. So, anyway, one of the drugs uh that does this is called rapamy. It's a It's the darling of the anti-aging. This is the Easter Island find, isn't it? Easter Island. Yes, Easter Island is connect. Yeah. Rapomy. Okay, let's So, rapomy was found in the soil of Easter Island in back from bacteria in in the soil of Easter Island that produced this compound which turns out to be an antifungal compound. And then they found out that it may have some properties against cancer. And then eventually they found out that it actually is an imunosuppressor and event and that's what made it get FDA approval as an imunosuppressive drug. Then much later it was found in a completely different place. It was found that it shuts down a major pathway in the cell and that pathway is related to the it's a pathway that senses nutrients. So it's related to caloric restriction. People then said okay let's see what happens if you give rapomy to mice and so on and mice lived a bit longer seemed a bit healthier. However rapomy is an imunosuppressive drug. So it's going to make you more prone to infections like steroids and and it has other side effects as well. Okay. So the question they have is can you adjust the dosage so you get the benefits against aging without this the the problems of imunosuppression and so on and that's still you know jury is still out on that. Yeah. Okay. Now there's also relativity where you can slow down time for yourself. Oh well that's going into space though. Yeah. Well well right that's one way to defeat aging right. However, you are still aging in your own body 1 second per second. The difference is all your friends are aging faster than you. Right. So, you're not going to live older than you would have as an organism, right? You'll just live longer than everybody else. Exactly. Isn't that the case? And then when you return, all your friends would have been dead. The Kelly the Kelly twins that did the experimental. Oh, yes. Yes. We we had one of them on on this program. Yes. Scott Kelly, astronaut who went up. That's right. And and his brother stayed here. Brother stayed here. They're identical twins and you can calculate how much younger one would have been. It's like a fraction of a second. They weren't. That's what he gained. He g he gained half a second, huh? Does it show? So basically basically Yeah. Does it show? Excellent. I don't remember the fraction, but it was they were not going so fast that the speed of light is the definition of sibling rivalry. The most expensive anti-aging regimen ever.

So as you surely know in physics we speak of this thing called entropy where left to itself a system will always degrade to uh lowest energy highest disorder and the key is left to itself. Yes. Yes. So we can create any manner of complexity on earth because we're not a closed system. We're open to the sun. So the sun is gaining entropy by helping us out. Eventually it's going to die and nothing's going to help it. Right. Right. So do you guys in molecular biology think of of entropy? There there's no question that uh entropic forces exist. But of course living systems all use external energy to keep it alive and part of the energy is used to do this maintenance and repair of the damage. But it never it's not perfect. And so eventually even if you keep repairing DNA damage, repairing cells, getting rid of defective cells, all of that stuff which takes energy, it's not perfect. And eventually the system gradually decays, but it means it decays at different rates for different species. Interesting. And or different parts different systems even within your own body. Oh, that's something that you that very interesting. So if you were to people were to analyze your different organs, they'd find that they they all had different ages. Yes. To to say someone's biological age, different ages mean different time distance from its birth to its death. Correct. Right. Because obviously it's all physically the same age. Physically chronologically it's the same age. Yes. But physiolog. But it doesn't make a difference cuz uh if I got a old heart and a young pancreas, I'm still going to die by with by a heart issue. With by a heart issue. Yes. So that was always what I suspected that people who live very long, all of their organs somehow are aging at the same rate physiologically. Well, I'm not I I don't know if that's true, but maybe uh they're still aging differently, but the the lead organ, the organ that's aging fastest is is still slower than other people. Right. Right. if they die, it's not going to be from that. So, given what you just said, it I didn't put two and two together here until just now in the second law of thermodynamics. Uh, one of its stipulations is if you have sort of usable energy over here and you convert it into another kind of energy over here, there's always energy losses. Always. That's why you cannot make a perpetual motion machine. Right. All right. And so uh the body is all about converting energy of one kind into another. You have chemical energy in food and you turn it into ATP. Yeah. Exactly. Remind us about that. We all learned it in biology class. The ATP cycle. Is that right? There's ATP is adnosin triphosphate. It's a high it's a molecule with high energy bonds. So you can think of it as a universal currency just like uh we in our world electricity is the universal currency. So you convert it to electricity then you can use that for everything and so the body uses it. So you can think of it as a kind of storeable form of energy that it can use right but it's taking energy from what it's taking energy from one thing and typically in our in our case we're getting it from carbohydrates and by burning carbohydrates it's chemical energy it's chemical energy so that energy is is used to make ATP. Got it. and anything else we make in our body to maintain our body temperature cuz we're warm-blooded to move. So, so it goes to thermal energy, kinetic energy, yeah, and the like and most of those things involve uh ATP and electrical energy and for your brain and your heart and signaling and all that. So, I'm just saying every time you convert from one form of energy to another, you're getting less energy than you started with. So, there is a decay in there. Yeah. Uh eventually. Interesting. Yeah.

So you describe this sort of implicit value of death to a species because it doesn't need you after a certain point of your fertility. We're beyond that now and we're what we call civilized. And so there are people who want to do anything they can to stay alive for as long as they can to stay alive for as long as they can. And you're in that business scientifically. What is the ethics? I I

should say my own lab has never worked on aging. I went from zero to expert in one book. Oh, okay. Okay. My my lab works on protein synthesis, which is a a central component of aging, but I don't actually do aging research myself.

Okay. But surely you've thought about the ethics of it. Yeah. Why wouldn't you? Oh, definitely. Yeah. Yes. Yes. And I also have no skin in the game. So that's uh okay that means we can get a very uh a truly objective other than beautifully soft skin. I missed that one though. Be ahead of you. I know that was a good call back. I like it.

Chemical laws, biological laws any in the way to stop us going from where we are now to potential immortality. Right? So there are two issues. One is is aging programmed? I mean are we all programmed to die? No. Because evolution doesn't care about it doesn't care about us dying. So there are genes that affect aging, but those genes don't exist in order to make us age. They were selected for some other reason, but they happen to cause us to age. So now that we understand some of the biology of aging, you ask, can we extend that? Yes. And there's no there are no physical or chemical laws to say that we have to die at 120.

Okay. I mean 120 is about the record. for very few reach that. And by the way, whenever you see a 120 year old, they're like, I am ready to go. I'm not sure. Disney World. Not all of them, but yeah. No, there's there's a woman, Jean Jean Calmont, who was the record holder at 122. Oh, she was a smoker and drinker. She was she used to smoke and drink into into her hundreds and and reporters after a while used to gather at her house every birthday. And one of them, at one of them, one of the reporters said, "Well, see you next year, I hope." And you know what she said? What? She said, "Sure, why not? You look pretty good to me."

So, but there's no physical or chemical law that says, you know, at 120, you got to go. There are species, as I said, that live 700 years, vertebrates. Of course, the question is, can we change our biology to make us live much longer and still keep us humans? You don't want to be a very slow metabolic animal like a Greenland shark. You still want to be human and you still want and you want to live much longer.

Now, there are people, I would say, at the one end of uh the anti-aging research community, including perhaps somebody you've had on your show, uh who think that it's it is possible. You can just keep extending life and that'll buy you enough time to do more research and you'll extend more life. And we eventually there's a generation that would reach the escape velocity. Exactly. Where the prolonging of your life is one year per year and then you live forever. Yeah. Yeah.

Now, I I'm highly skeptical as are most scientists in this field because aging is a is a multiffactorial process and to be able to do this in a way that's safe, that's efficacious, that actually works, I think it's it's going to be very very hard. So, not impossible. the Google software that uses AI for folding proteins which won a Nobel Prize if if memory serves. Won't that solve all your protein folding problems? No, this is this is different from I I think AI will have a big influence on biology and maybe one day it will help with uh things like aging. One day 18 months from now sometime in the distant progressing in the future distant future of AI. What time is it?

Okay, let's say I'm I'm highly skeptical, but but there is no physical law. But I I'd say there's also no physical or chemical law that says you can't colonize other galaxies or even Mars. And so why would we want to, you know, whatever Elon may say, it's not going to happen tomorrow. So I think and I think we should get down here kind of worked out first. I'm sorry, but our own problems. Yeah. Why don't we make this place habitable?

All right. So what happens the day we as chiefs escape velocity? What happens to civilization? I I think before that a number of things will happen. For example, more people uh may live to be 100 or or well into their 90s or early hundreds. That itself will cause a huge shift in society. For example, fertility rates everywhere are dropping dropping. And so what you're going to have is a population. Yeah. society where there's very little turnover. Same people are living longer and longer, very very slow turnover.

To me that means a less dynamic and less vibrant society. If you look at the history of science or any fields even literature, people are have done their most creative work when they're young. And it's not just about physiological age. When you're young, you're you're you're looking at things fresh. you you're not as opinionated. You you don't have you're not dogmatic. And that allows you to think out of the box. You have to convince the old people that they're less useful to society. How do you Well, that's well, one of the reasons I'm retiring is because, you know, I decided four or five years ago to close down my land. It's going to happen late this year. It's partly because I do believe that when you've had your time, you know, you should step aside and let younger people carry on. Carry on.

When Einstein was given the option to be operated on basically on his deathbed, he said, "No, my work is done." My work is done. Yeah. I would have said, "What kind of doctors are you that saved me?" See, the thing is what Thank you, what you were talking about is inverting the population pyramid. So, it goes from a small peak of aging population to a rather large one and less young people. I mean, we are basically diving down a drain here. What would be it would be it would be more stable the whole time. more stable stable thing would be good but if the turnover is very slow and people just live for very long. I mean, as people get older, they accumulate power, they accumulate wealth, they accumulate influence, and of course, the three go together. And that then means that it's harder for younger people uh to gain to gain entrance to to make it and so on. That's a real cultural fact. Yes. And that's a that's a real problem. That's we're seeing that right now in a certain party in in America where they're like, "Yo, everybody who is in charge is 80 years old. Get out of the way because we have a different way to do things and we want to get to it." Interesting. And so, so I think societies would be more stagnant and less dynamic and less creative. People will always throw exceptions at me. Oh, so and so was so brilliant all late in life. But those are exceptions. You know, that's not what you plan a society around. Yeah.

But here's the problem. If somebody gave you a pill and said, "This is going to give you 10 extra years of healthy life." Nobody wants to be sick for 10 years. 10 years of extra healthy life. Would you take it? I know I would. Yes. Okay. Almost all of us would. And this is the conflict between what we as individuals want and what's good for society. And that's because at the end of those 10 years, if you're given the option again, you'll probably say yes again. Exactly right. Absolutely. That takes especially if it's healthy life.

So So that thought experiment takes the larger question down to its individual parts and you realize people really do want to live forever. They they do well cuz Yeah, they do. Because this is, as you say, the only life we know. It's our existence. We we fear the the loss of existence. And that's that's you know there's I mean I'm I'm about to get philosophical. The great thing about death is that when you look at it fullon and embrace it for what it is, it allows you to wake up and treat each day as something special because you know this thing is going to be over. If you take that away, you know, I don't give a damn. Like, you know, people have said that that having a finite life gives you the drive, the incentive to accomplish things. Otherwise, there's always tomorrow. There's always tomorrow.

Okay. So that that is true but at the same time there's an old joke who would want to live to be 100 and the answer is always someone who's 99. Exactly. So you you may you may be philosophical about death in the abstract. You don't want to die next year. Well no you're absolutely right. I don't want to die period. You know cuz my life is pretty damn good. So you know as long and we're not talking about people who are so mortally injured or or ill that death feels like an escape. We're talking about someone who's fully who's vibrant. Vibrant. Yes.

There's also one aspect of aging research. If you tell if you ask most of them, they they'll say except for some of these outliers, they'll say, "Oh, we're not about extending lifespan. We're about increasing health in your life." And the idea is that you stay healthy all your life and then suddenly, you know, crash and die. And there's a poem called The One Horse Open Shay. I just learned about that poem. It's it's the horse that the carriage was perfectly designed so that it wore out at all its parts wore out equally exactly at the same time and one one minute the farmer was riding along the next minute he was on the ground surrounded by a bunch of debris cuz his whole carriage collapsed. Now, that's what people are are asking when when you say we're going to compress the period of morbidity in old age and we're just going to suddenly decline and die. Nobody's shown that that can actually happen. Uh Apple is working on it. Believe me, nobody's shown that.

So, if they increase our health span, it's equally possible that they lip span. Good phrase. Not lifespan, health span. Yeah. But if they do that, if they keep us healthy in old age, it's equally possible that they extend our lives too. And that eventually we still have that slow decline. You still have the you just reach a point where now I'm 108 and it's all falling apart, but I'm not going to die tomorrow. It's still going to be a slow hard death 5 years from now. Yeah. Yeah.

Of course, if we live forever, we need to find another planet because the population will continue to rise and we will outstrip the resources of Earth and possibly Mars, Venus, and any place else we search for. That isn't quite true. For example, what? Okay, if birth rate went to zero, then it's not a problem. Exactly. But who wants that? Well, first of all, you're not going to have complete immortality. You're going to have extended lifespan. So the birth rate simply has to fall in accordance with how much you've increased your lifespan. And in fact, if you look at Korea, South Korea, it's happening. People are living longer and yet the population is going down.

So Vanki, this conversation has been delightful and illuminating and enlightening and I can't wait to die. You're going to have to. And after we're done with this episode, he's going to whisper to us that he's 150. On this topic of why we die, we covered so many nuances of it. I'm left with very little to offer as a cosmic perspective. What I will say is that speaking for myself, echoing the sentiments of others, I at this stage in my life value the knowledge that I will die because that gives meaning to every day that I'm alive. Knowing that there's one fewer days left in my future to love, to have new ideas, to make discoveries, to embrace all that it is to be alive in this world. If you look at it mathematically, if the knowledge of death is what brings meaning to being alive, then to live forever is to live a life with no meaning at all. If you can just put off to tomorrow what you could have done today.

Will I think this on my deathbed? If I'm offered a pill that can make me live another 10 years when I'm on my deathbed, would I take that pill? I don't know. It's kind of easy to talk about death when I'm pretty sure I'm not near it in this moment. But I will say I reserve the right to revisit the option of living a little longer when I'm on my deathbed. But for now, knowing I'm going to die is what's keeping me going. And that is a cosmic perspective. Chuck, good to have you, man. Always a pleasure, Gary. Pleasure, my friend.

Hello there. This has been Star Talk special edition topic, why we die. Until next time, Neil Degrass Tyson, your personal astrophysicist. Keep looking up. [Music]