WEBVTT - Why do we age? (featuring Dr. Venki Ramakrishnan) 0:00:07.800 --> 0:00:10.280 They say that only two things in life are certain, 0:00:10.920 --> 0:00:14.760 death and taxes. For the lucky among us will pass 0:00:14.800 --> 0:00:18.520 away quietly at an old age. But why is aging 0:00:19.000 --> 0:00:24.400 and thus death inevitable? And how do we even define aging? Yes, 0:00:24.480 --> 0:00:26.400 you can define it by the ticking of the clock, 0:00:26.920 --> 0:00:29.639 but is there a biological way to define it that 0:00:29.720 --> 0:00:32.720 gives you a better shot at really understanding how the 0:00:32.760 --> 0:00:36.159 passage of time has worn away at your body. If 0:00:36.200 --> 0:00:38.880 two people in their thirties can mix their old cells 0:00:38.920 --> 0:00:42.120 together to make a brand new baby, then why can't 0:00:42.159 --> 0:00:46.720 those same two people just start making young cells for themselves? 0:00:47.240 --> 0:00:50.760 And shouldn't evolution favor living a really long time so 0:00:50.800 --> 0:00:53.199 we can make more babies and be around to help 0:00:53.240 --> 0:00:57.520 them grow. Aging can be a counterintuitive phenomenon, and Daniel 0:00:57.560 --> 0:01:01.520 and I get many questions from our audience the extraordinaries 0:01:01.880 --> 0:01:06.240 about the aging process. However, despite the furrows in my 0:01:06.319 --> 0:01:09.240 forehead that get deeper each year and that my son 0:01:09.400 --> 0:01:13.600 sometimes stares at, this biologist is not an expert in 0:01:13.640 --> 0:01:16.440 the science of aging. But lucky for us, we were 0:01:16.480 --> 0:01:20.560 able to get doctor Venki Ramakrishnan, author of Why We Die, 0:01:20.959 --> 0:01:23.920 The New Science of Aging and The Quests for immortality 0:01:24.240 --> 0:01:28.200 to come onto the show to answer your questions. Welcome 0:01:28.280 --> 0:01:31.560 to Daniel and Kelly's extraordinarily Old Universe. 0:01:44.920 --> 0:01:45.120 Hi. 0:01:45.319 --> 0:01:48.840 I'm Daniel. I'm a particle physicist. I round my age 0:01:48.880 --> 0:01:49.760 up two hundred. 0:01:50.040 --> 0:01:53.640 Hello. I'm Kelly Waidersmith. I study parasites and space And Daniel, 0:01:53.720 --> 0:01:56.760 last time we talked, you rounded up to fifty. Have 0:01:56.880 --> 0:01:59.240 you just decided that, now that you're fifty, yere rounding 0:01:59.320 --> 0:02:01.320 up to one hundred because that is not a helpful 0:02:01.400 --> 0:02:02.040 wait around. 0:02:03.920 --> 0:02:06.280 I think that's totally consistent. When I was forty eight, 0:02:06.320 --> 0:02:08.679 I called myself fifty, and now that I'm fifty, I 0:02:08.720 --> 0:02:11.040 got a round up to one hundred. It totally makes sense, 0:02:11.360 --> 0:02:13.720 not to me. Plus, I think I look pretty good 0:02:13.720 --> 0:02:14.200 for one hundred. 0:02:14.280 --> 0:02:16.840 Yeah, you look great for one hundred, But I say 0:02:16.919 --> 0:02:18.160 you look good for fifty two. 0:02:18.400 --> 0:02:19.920 But like, I don't. 0:02:20.000 --> 0:02:21.760 Yeah, I know that that kind of rounding doesn't make 0:02:21.760 --> 0:02:23.120 sense to me. But that's all right, all right. 0:02:23.200 --> 0:02:25.960 So here's my question for you today, Kelly. If you 0:02:26.000 --> 0:02:28.160 could take a pill that would extend your life to 0:02:28.240 --> 0:02:31.320 a thousand years or a million years, would you do 0:02:31.360 --> 0:02:34.240 you want to live a super crazy long life? 0:02:34.680 --> 0:02:39.200 Umm? Al right, So one, okay, So selfishly, I would 0:02:39.240 --> 0:02:41.600 need to know about the quality of that life, and 0:02:41.680 --> 0:02:43.400 if the quality of my life was going to be 0:02:43.440 --> 0:02:45.239 as good it is now, for all of that time, 0:02:45.320 --> 0:02:48.120 I would think about it. But to be honest, the 0:02:48.160 --> 0:02:50.400 only reason I'm thinking that I might want to say 0:02:50.440 --> 0:02:52.560 yes is that I want to live at least as 0:02:52.560 --> 0:02:55.359 long as my son lives, because he's going to need 0:02:55.440 --> 0:02:57.360 care his whole life, and I don't want him to 0:02:57.360 --> 0:02:59.680 ever be alone. And so if I could live as 0:02:59.720 --> 0:03:02.799 long as he lives, one hundred percent, So what about. 0:03:02.600 --> 0:03:05.440 You, No, I see, life is like a hike. You know, 0:03:05.520 --> 0:03:08.639 hikes are wonderful. There's oneful moments you're glad you went 0:03:08.720 --> 0:03:11.760 on them. You're also glad when they're over. Nobody wants 0:03:11.800 --> 0:03:13.800 to be in a hike that lasts until the end 0:03:13.800 --> 0:03:16.519 of the universe. And maybe sometimes the best part of 0:03:16.560 --> 0:03:17.960 a hike is when you get to sit down at 0:03:17.960 --> 0:03:22.480 the end, you're like, oh wow, what a nice walk done. 0:03:22.880 --> 0:03:26.000 Especially at the end of a good hike, Yeah, you're like, ah, 0:03:26.200 --> 0:03:27.600 all right, I'm ready to be done. 0:03:27.639 --> 0:03:27.919 Exact. 0:03:28.120 --> 0:03:30.400 And my grandpa passed away recently, and I think he 0:03:30.480 --> 0:03:33.160 had that kind of life. He hiked it was a 0:03:33.200 --> 0:03:35.600 good trip, and at the end he told everyone, he's like, 0:03:35.920 --> 0:03:38.040 I'm ready, and then he passed away into sleep, and 0:03:38.080 --> 0:03:40.600 I was like, man, I really hope that's in the 0:03:40.680 --> 0:03:42.840 genes somewhere, because that's pretty solid. 0:03:42.960 --> 0:03:45.680 And I hope that listening to this podcast has improved 0:03:45.680 --> 0:03:48.560 that everybody's quality of life out there were making your 0:03:48.680 --> 0:03:50.600 hike through life more pleasant. 0:03:50.840 --> 0:03:53.440 Maybe it will improve their quality of sleep, which at 0:03:53.480 --> 0:03:56.040 the end of the episode will discover is an important 0:03:56.040 --> 0:03:58.760 part of being healthy. So we're doing our part. 0:03:59.080 --> 0:04:03.280 You're saying that listening to the podcast could technically scientifically 0:04:03.440 --> 0:04:04.560 extend your lifespan. 0:04:06.080 --> 0:04:09.360 Maybe maybe listen to our prior episodes about how you 0:04:09.440 --> 0:04:14.200 evaluate scientific statements and see what you think, dear listeners, 0:04:14.920 --> 0:04:15.560 and whether. 0:04:15.360 --> 0:04:17.920 You should believe people who have skin in the game exactly. 0:04:18.040 --> 0:04:20.640 Yes, all right, Well, so we get loads and loads 0:04:20.680 --> 0:04:23.640 of questions about aging from the extraordinaries, and so I 0:04:23.720 --> 0:04:27.159 pulled them all together. We found an amazing expert to 0:04:27.200 --> 0:04:30.440 answer the question. Amazing, amazing, he does such a great job. 0:04:30.520 --> 0:04:31.800 How do you know this Nobel Prize? 0:04:32.040 --> 0:04:37.480 Kelly Oh, thanks for pitching myte We both were on 0:04:37.520 --> 0:04:40.719 the short list for the Royal Society Book Prize. Yep, 0:04:40.800 --> 0:04:44.000 Why We Die is thank you Rama Christnan's book, and 0:04:44.040 --> 0:04:46.560 A City on Mars was my book, and we both 0:04:46.560 --> 0:04:48.440 made the short list for the Royal Society Prize. 0:04:48.520 --> 0:04:51.279 And you're just gonna omit those crucial piece of information 0:04:51.360 --> 0:04:53.960 that you won the prize. So Kelly is the author 0:04:54.000 --> 0:04:56.880 of a book which edged out a Nobel Prize winning 0:04:56.920 --> 0:04:57.960 nonfiction science book. 0:04:58.160 --> 0:05:01.800 I was not gonna mention that. Thank you for ult 0:05:02.800 --> 0:05:03.560 over the years. 0:05:03.800 --> 0:05:08.200 I appreciate it, all right, Well, this is a wonderful 0:05:08.240 --> 0:05:12.800 conversation with a deep expert who also has the unusual 0:05:12.880 --> 0:05:15.880 quality of being able to explain things clearly yes. 0:05:15.720 --> 0:05:18.279 And being so nice, so nice. 0:05:18.480 --> 0:05:18.640 Yeah. 0:05:18.680 --> 0:05:20.360 Anyway, So I had so much fun. I feel so 0:05:20.480 --> 0:05:21.240 lucky we got to do. 0:05:21.200 --> 0:05:24.400 This interview before we bring on our expert, who want 0:05:24.400 --> 0:05:26.680 to know abel prize in this area. We asked you 0:05:26.760 --> 0:05:30.520 guys what you thought was the reason for aging. Here's 0:05:30.560 --> 0:05:31.960 what people had to say. 0:05:32.400 --> 0:05:36.279 I underested it to be oxidative pressures where new copies 0:05:36.320 --> 0:05:38.960 of things just aren't quite as good as they used 0:05:39.000 --> 0:05:42.440 to be and there are errors throughout. Short answer telemeres 0:05:42.880 --> 0:05:45.280 real answer, so that there's someone to say I wouldn't 0:05:45.320 --> 0:05:47.880 do that if I were you to the younger generations, 0:05:48.240 --> 0:05:50.839 it's not like the clouds are going to yell at themselves. 0:05:50.880 --> 0:05:56.359 Certain proteins that mark ourselves or do something along the 0:05:56.400 --> 0:06:03.200 lines of maintaining how are unique gets repeated or transcripted deggregate. 0:06:03.279 --> 0:06:04.640 Over time, the. 0:06:04.680 --> 0:06:07.479 Body forgets how to make a new body the way 0:06:07.480 --> 0:06:08.240 that it once did. 0:06:08.600 --> 0:06:11.960 We age as a consequence of too many gas station burritos, 0:06:12.160 --> 0:06:15.080 ninety nine cent big gulps and betrayal by Teilomeir. 0:06:15.440 --> 0:06:18.440 At a molecular point of view, it's really hard to 0:06:18.480 --> 0:06:23.239 maintain consistency in the gazillion times molecules and the cells 0:06:23.320 --> 0:06:26.560 needs to produce these error skips that canap until the 0:06:26.680 --> 0:06:28.280 whole body the case, my. 0:06:28.320 --> 0:06:31.239 Short answer is we age due to the passage of time. 0:06:31.600 --> 0:06:34.800 I think we age because we need to die ultimately. 0:06:35.520 --> 0:06:38.800 I think it's conducive, if not crucial, to the evolution 0:06:38.880 --> 0:06:43.599 of life itself, for organisms to have a finite lifespan. 0:06:43.680 --> 0:06:45.480 Every beginning as an end. 0:06:46.000 --> 0:06:48.720 So I believe I've read somewhere that the reason why 0:06:48.800 --> 0:06:52.680 we age is because there is a shortening of some 0:06:52.760 --> 0:06:57.160 kind of a protein or molecule within our cells. 0:06:57.960 --> 0:07:03.400 And so for DNA current to fray and just gets 0:07:03.680 --> 0:07:05.120 left up to entropy. 0:07:05.640 --> 0:07:09.440 Aging and death are just part of the evolutionary. 0:07:08.839 --> 0:07:11.520 Process and processes that have brought us to where we 0:07:11.520 --> 0:07:12.040 are today. 0:07:12.320 --> 0:07:13.200 It's just a fact. 0:07:13.520 --> 0:07:17.680 Thanks everybody for your speculation on this concept. Now let's 0:07:17.760 --> 0:07:19.920 talk to the expert and find out what we know 0:07:20.200 --> 0:07:21.280 and what we don't know. 0:07:21.600 --> 0:07:24.800 Doctor. Thank you. Rama Krishnan was initially interested in physics, 0:07:24.840 --> 0:07:26.440 but I'm going to go ahead and give a point 0:07:26.440 --> 0:07:29.640 to biology because he transitioned to focusing more on this 0:07:29.760 --> 0:07:32.480 field and the biology stuff worked out well for him 0:07:32.520 --> 0:07:34.800 because in two thousand and nine he received a Nobel 0:07:34.840 --> 0:07:38.120 Prize for his work on ribosomes. He was President of 0:07:38.160 --> 0:07:40.960 the Royal Society from twenty fifteen to twenty twenty and 0:07:41.080 --> 0:07:44.160 recently wrote the book Why We Die, The New Science 0:07:44.200 --> 0:07:47.400 of Aging and the Quest for Immortality. And today we'll 0:07:47.400 --> 0:07:50.080 be talking about the science of aging. Welcome to the show. 0:07:50.360 --> 0:07:51.920 Thank you, and thank you for having me. 0:07:52.080 --> 0:07:53.920 Yeah, we're super excited to have you. We get so 0:07:54.080 --> 0:07:56.960 many questions from our audience about aging, and every time 0:07:57.080 --> 0:07:58.840 I'm like, look, I know when you look at me, 0:07:58.920 --> 0:08:02.640 I look like the right person to ask about. 0:08:01.920 --> 0:08:06.640 Well, they should look at me then, and there's so 0:08:06.720 --> 0:08:09.840 much discussion out there about aging and how to prevent 0:08:09.880 --> 0:08:12.520 it and if it's possible, and so much snake oil 0:08:12.600 --> 0:08:14.840 being sold out there. It's so important to cut to 0:08:14.880 --> 0:08:15.320 the chase. 0:08:15.560 --> 0:08:19.440 It's certainly having a moment, and I'm a little bit cynical. 0:08:19.680 --> 0:08:22.760 I think it has to do with my generation, the 0:08:22.760 --> 0:08:28.000 boomer generation, that's used to having everything it wanted in life, 0:08:28.120 --> 0:08:34.400 suddenly coming to terms with getting old, and so, you know, 0:08:34.480 --> 0:08:38.800 there's a lot of anxiety in the air. Although having 0:08:38.840 --> 0:08:43.120 said that, you know, this fear of death and fear 0:08:43.160 --> 0:08:48.000 of aging is simply as old as humans, you know, 0:08:48.120 --> 0:08:52.320 because ever since we learned about mortality, we've fretted and 0:08:52.400 --> 0:08:55.920 worried about it. And I like to say we may 0:08:55.920 --> 0:09:00.000 be the only species that's aware of mortality. Other animal 0:09:00.760 --> 0:09:05.040 maybe are aware of death, but they're not aware that 0:09:05.400 --> 0:09:08.679 they all have a finite lifespan and everybody is going 0:09:08.720 --> 0:09:12.480 to die. I'm not sure that other species have that 0:09:13.400 --> 0:09:18.679 understanding that we do. And when we somehow obtain that understanding, 0:09:18.880 --> 0:09:23.719 perhaps as a result of cognitive development, language and so on, 0:09:25.080 --> 0:09:28.480 ever since then, it has become it became a theme 0:09:29.240 --> 0:09:32.000 and if you look at most religions. They're all about, 0:09:32.559 --> 0:09:35.360 you know, how to deal with death and what happens 0:09:35.400 --> 0:09:36.479 after we die. 0:09:36.520 --> 0:09:38.040 I don't know if it's a blessing or a curse 0:09:38.080 --> 0:09:39.440 that our species is aware of that. 0:09:40.280 --> 0:09:43.760 Yeah, I mean many species aren't even aware of death, 0:09:43.800 --> 0:09:45.120 you know, it just simply happens. 0:09:46.520 --> 0:09:48.760 Well, can I start us off with a very broad 0:09:48.840 --> 0:09:52.720 sort of philosophical question, which is, how do you define 0:09:52.840 --> 0:09:56.160 aging biologically? Because as a physicist, I might think, well, 0:09:56.360 --> 0:09:58.560 you have a clock and it starts and it stops, 0:09:58.640 --> 0:10:02.160 and that's your age. But we're interested in more than that, right, 0:10:02.200 --> 0:10:04.720 It's some sort of like decrease in the quality of life. 0:10:04.800 --> 0:10:08.400 You're gradually moving towards death. It's this fact that you 0:10:08.400 --> 0:10:10.959 don't just like live for sixty two years and then poof, 0:10:11.000 --> 0:10:15.360 you're done. Your body degrades. How do we define aging 0:10:15.440 --> 0:10:16.960 in a crisp way scientifically? 0:10:17.320 --> 0:10:22.120 Yeah, so it's not. It's definitely related to the chronological 0:10:22.240 --> 0:10:26.520 clock to time, but the rate is very different, not 0:10:26.600 --> 0:10:31.480 only for species, it's vastly different for species, but it's 0:10:31.480 --> 0:10:34.240 also different for individuals within a species. If you go 0:10:34.320 --> 0:10:37.880 to your high school reunion, you will immediately be aware 0:10:37.920 --> 0:10:41.199 of that the fact that people don't age at the 0:10:41.240 --> 0:10:47.600 same rate, and I think aging molecular biologists would define 0:10:47.600 --> 0:10:54.000 it as the gradual accumulation of changes and damage to 0:10:54.320 --> 0:10:59.280 us over time that can happen different rates in different individuals. 0:10:59.800 --> 0:11:04.000 And it's not just damage. Some of it has changes 0:11:04.120 --> 0:11:08.720 that occur with time. It may occur at different rates 0:11:08.720 --> 0:11:12.800 in different individuals, and these changes may have a purpose 0:11:12.920 --> 0:11:17.760 early in life, for example, modifications of our DNA, but 0:11:17.880 --> 0:11:21.560 they cause us or at least they're strongly correlated with 0:11:21.679 --> 0:11:27.199 aging later in life. So that's how I define it. 0:11:27.280 --> 0:11:32.920 And this accumulation of changes in damage leads to a 0:11:32.960 --> 0:11:37.480 gradual loss of function, and when that loss of function 0:11:37.720 --> 0:11:45.040 reaches some point where some critical system fails, then you 0:11:45.120 --> 0:11:49.480 have death. And so a death is a result of aging, 0:11:49.800 --> 0:11:53.680 but its exact moment can't be predicted because in a 0:11:53.720 --> 0:11:58.400 complex system, you can't predict exactly when a critical component 0:11:58.480 --> 0:11:59.080 will fail. 0:12:00.320 --> 0:12:03.760 Aging and changes, but that must mean very different things 0:12:04.040 --> 0:12:06.240 to different parts of your body. You're talking about your 0:12:06.280 --> 0:12:09.720 nerves or your skin or your eyes. Are there ways 0:12:09.840 --> 0:12:10.960 we have to measure it? 0:12:10.960 --> 0:12:14.120 It happens at every level. It happens at every level. 0:12:14.240 --> 0:12:17.800 But I would say fundamentally it happens at the molecular level, 0:12:18.679 --> 0:12:25.360 and that then manifests itself and each increasing level of complexity. 0:12:25.480 --> 0:12:28.960 So you can go from molecules to collection of molecules 0:12:28.960 --> 0:12:33.480 in our cell, to components of the cell, to cells themselves, 0:12:34.040 --> 0:12:39.120 and then entire tissues, and you know the way cells 0:12:39.160 --> 0:12:42.240 communicate with each other, like our immune system. So you 0:12:42.280 --> 0:12:46.280 can see that, you know, it happens at the molecular level, 0:12:46.760 --> 0:12:53.080 but it starts manifesting itself at increasingly higher levels, you know, 0:12:53.200 --> 0:12:57.320 until the point that you know, we see aging as 0:12:57.559 --> 0:13:01.840 various forms of frailty, you know. So in fact, a 0:13:01.920 --> 0:13:04.600 very good measure of aging is actually something called the 0:13:04.640 --> 0:13:08.120 frailty index. They'll measure things like can you get out 0:13:08.120 --> 0:13:11.920 of bed? How fast can you walk you know, fifty yards? 0:13:12.679 --> 0:13:16.040 What's your grip strength? How good is your eyesight? How 0:13:16.080 --> 0:13:19.280 good is your cognition? You know, how good is your memory? 0:13:19.640 --> 0:13:23.439 So all of those things are indications of frailty at 0:13:23.440 --> 0:13:28.200 a macroscopic level, at a level that you and I experience. 0:13:28.880 --> 0:13:32.160 But ultimately the underlying causes are molecular. 0:13:31.880 --> 0:13:34.760 Okay, and is aging universal. So we're getting to one 0:13:34.800 --> 0:13:38.079 of our first listener questions right now. One of our 0:13:38.080 --> 0:13:42.000 listeners noted that they had heard stories about immortal organisms 0:13:42.360 --> 0:13:44.560 and they wanted to know are they actually immortal. 0:13:45.160 --> 0:13:49.920 Yeah, I had to say, there's a lot of hype. 0:13:50.000 --> 0:13:53.720 What happens is people will study an organism that ages 0:13:53.840 --> 0:13:57.400 very slowly, and suddenly they'll say, oh, this has no 0:13:57.640 --> 0:14:01.319 sign of biological mortality. Let me back up and explain 0:14:01.400 --> 0:14:06.280 what I mean by that. So, in normal species, the 0:14:06.679 --> 0:14:09.200 likelihood of that we are going to die at any 0:14:09.200 --> 0:14:14.440 given time keeps increasing exponentially. So for example, that chances 0:14:14.480 --> 0:14:17.560 that you'll die when you're ten are very small, but 0:14:17.640 --> 0:14:21.440 the chances you'll die in the next year when say 0:14:21.480 --> 0:14:26.040 you're ninety five or one hundred or almost fifty percent, okay, 0:14:26.600 --> 0:14:32.400 so the chances keep going up. Now, in some organisms, 0:14:32.520 --> 0:14:37.680 it appears that that likelihood of dying you know, of 0:14:37.840 --> 0:14:41.160 aging events, not of being eaten by a predator or 0:14:41.160 --> 0:14:45.400 starving or anything else. Those are called external causes. But 0:14:45.440 --> 0:14:51.280 you know aging, just dying of aging, that probability doesn't 0:14:51.320 --> 0:14:55.320 seem to go up with time. And so there are 0:14:55.320 --> 0:15:00.440 some species, like a freshwater species called the hydra. There's 0:15:00.480 --> 0:15:05.240 another species called the immortal jellyfish, and these tend not 0:15:05.320 --> 0:15:09.080 to show any signs of biological aging. That is, the 0:15:09.240 --> 0:15:12.040 likelihood it's going to die just doesn't seem to change 0:15:12.760 --> 0:15:17.560 with time. But in fact what is happening is it's 0:15:17.600 --> 0:15:21.480 probably aging very very slowly. So if you looked, if 0:15:21.480 --> 0:15:25.560 you simply followed a hydra in the wild, it'll die 0:15:25.560 --> 0:15:28.440 of some other cause, not of old age. But if 0:15:28.440 --> 0:15:31.640 you kept it safe and followed it long enough, you 0:15:31.720 --> 0:15:36.920 will find that it too, gradually ages because no regeneration 0:15:37.360 --> 0:15:41.840 is perfect. You know, the reason hydra and jellyfish appear 0:15:41.960 --> 0:15:46.480 not to age is they constantly regenerate their tissue using 0:15:46.520 --> 0:15:50.640 specialized cells called stem cells. In a way, they're like plants. 0:15:50.720 --> 0:15:53.760 You know, plants have stem cells all over themselves, and 0:15:53.800 --> 0:15:56.040 that's why you can take a cutting from a plant 0:15:56.080 --> 0:15:59.760 and you know, grow an entirely new tree with it. Right, 0:16:00.600 --> 0:16:03.400 we can't do that, but you know, some animals regenerate, 0:16:03.520 --> 0:16:05.560 like starfish. You know, it cut off an arm and 0:16:05.600 --> 0:16:09.600 it'll regenerate an arm. And you know, some of these 0:16:09.640 --> 0:16:15.400 species can regenerate, you know, any tissue, and but it's 0:16:15.400 --> 0:16:18.360 not perfect. And so I would say to your listener 0:16:19.360 --> 0:16:22.840 that yes, everything will die, but they die at different rates. 0:16:23.360 --> 0:16:25.119 I mean, they age at different rates. 0:16:25.160 --> 0:16:29.280 And so everything ages. It's universal across organisms. Do we 0:16:29.400 --> 0:16:33.520 understand why we age? Like, is it an inevitability of 0:16:33.600 --> 0:16:37.400 like thermodynamics or molecular copying or something, or is it 0:16:37.440 --> 0:16:39.200 an evolutionary advantage? 0:16:39.320 --> 0:16:41.920 Well, there there are two ways of looking at it. 0:16:42.000 --> 0:16:45.720 One is, you know, the physicist way would be that 0:16:46.000 --> 0:16:49.560 you know, second law wins and there's always increase in 0:16:49.800 --> 0:16:53.720 entropy and disorder and eventually things sort of degrade. And 0:16:53.800 --> 0:16:57.840 you know, life is not a you know, equilibrium system. 0:16:58.280 --> 0:17:00.680 The problem with that is that life is not a 0:17:00.720 --> 0:17:06.000 closed system, and if you apply enough energy and enough 0:17:06.080 --> 0:17:10.600 resources you can reverse damage. And in fact that's what 0:17:10.640 --> 0:17:14.480 we do. So why is it then that we age 0:17:14.480 --> 0:17:18.240 and die? Well, I'll tell you the evolutionary argument. The 0:17:18.240 --> 0:17:23.639 evolutionary argument is resources are limited and throughout our history 0:17:23.640 --> 0:17:27.639 and in fact, until recently, resources were limited for humans 0:17:27.680 --> 0:17:30.359 as well. You know, we had to struggle to have 0:17:30.480 --> 0:17:34.280 enough food to live and so on. When resources are limiting, 0:17:35.280 --> 0:17:38.000 the organism has a choice to make. Does it put 0:17:38.160 --> 0:17:44.760 more of the resources into maintenance and repair, which requires energy, 0:17:44.920 --> 0:17:50.560 requires food, et cetera. Or should those resources be put 0:17:50.560 --> 0:17:55.040 in too rapid growth and development? Now, if you take 0:17:55.080 --> 0:17:57.960 a mouse. For example, a mouse lives about two years, 0:17:58.600 --> 0:18:02.600 whereas a blue whale lives a few hundred years. So 0:18:02.640 --> 0:18:06.359 why is it that there's this vast difference. Well, the 0:18:06.400 --> 0:18:10.680 evolutionary argument is that evolution doesn't actually care how long 0:18:10.720 --> 0:18:16.439 you live. Evolution simply cares about how successful are you 0:18:16.480 --> 0:18:19.080 going to be at passing on your genes because it's 0:18:19.119 --> 0:18:23.720 selecting for those genes, it's not really selecting for you 0:18:23.760 --> 0:18:28.520 as an individual. And so in the case of a mouse, 0:18:28.560 --> 0:18:32.720 there's no point in spending a lot of resources getting 0:18:32.760 --> 0:18:35.520 a mouse to live to be forty years. And the 0:18:35.600 --> 0:18:38.560 reason is that long before that it'll be eaten, or 0:18:38.600 --> 0:18:41.960 it'll die of starvation or in a drought, or all 0:18:42.240 --> 0:18:46.800 of a zillion external causes. And so in the case 0:18:46.840 --> 0:18:51.160 of a mouse, it's more advantageous from an evolutionary point 0:18:51.200 --> 0:18:54.280 of view for a mouse to grow very rapidly, produce 0:18:54.320 --> 0:18:57.399 lots of offspring, and then you know, it doesn't matter 0:18:57.520 --> 0:19:02.119 whether it dies, Whereas with larger animals, their metabolism is 0:19:02.160 --> 0:19:06.120 also slower, so they take longer to mature, their offspring 0:19:06.160 --> 0:19:11.600 take longer to produce and grow up and mature, and 0:19:11.680 --> 0:19:16.280 so in there it does make sense for evolution to 0:19:16.400 --> 0:19:22.200 have selected for longer lifespan in order to ensure fitness. Okay, 0:19:22.200 --> 0:19:25.639 because otherwise it may men not actually have the chance 0:19:25.720 --> 0:19:30.480 to reproduce, or not to reproduce enough. And it gets 0:19:30.520 --> 0:19:34.440 worse than that. It's not even that evolution doesn't care 0:19:34.840 --> 0:19:38.720 what happens to you after you've produced your offspring. Evolution 0:19:38.960 --> 0:19:42.560 also will select for traits that are advantageous early in 0:19:42.640 --> 0:19:47.640 life that will get you to maturity and reproduction, even 0:19:47.720 --> 0:19:51.520 if those exact same traits will cause you to age 0:19:51.600 --> 0:19:54.600 later in life. And there are many examples of that 0:19:55.400 --> 0:19:59.000 in my book. For example, certain mechanisms that cause us 0:19:59.000 --> 0:20:02.600 to age may have evolved as anti cancer mechanisms. Now, 0:20:02.640 --> 0:20:05.320 of course you want to prevent cancer early in life, 0:20:06.000 --> 0:20:09.520 but later in life they may cause aging, and ironically, 0:20:09.560 --> 0:20:14.400 cancer itself increases as we age the likelihood of getting cancer. 0:20:14.600 --> 0:20:16.080 But that's a different story. 0:20:16.119 --> 0:20:18.240 Can you give us an example of an anti cancer 0:20:18.240 --> 0:20:19.400 strategy that causes aging? 0:20:19.480 --> 0:20:24.000 Leader Yeah, sure so. One very classic example is that 0:20:24.800 --> 0:20:27.760 most of the cells in our body can only divide 0:20:27.760 --> 0:20:30.439 a certain number of times, and then they reach a 0:20:30.480 --> 0:20:36.399 state called sinesence. Senessen cells are these dysfunctional cells that 0:20:36.480 --> 0:20:42.880 can't divide and they actually secrete inflammatory compounds. And as 0:20:42.920 --> 0:20:46.719 we age, we accumulate more sinescent cells and that becomes 0:20:46.720 --> 0:20:51.080 a problem and inflammation becomes a problem. Now, why do 0:20:51.359 --> 0:20:55.200 cell stop dividing? Well, it turns out that our chromosomes 0:20:55.240 --> 0:20:59.920 are linear DNA molecules and their ends are specialized struck. 0:21:00.200 --> 0:21:04.840 It is called telomeres. Now, the copying mechanism for DNA, 0:21:04.880 --> 0:21:07.320 every time it cell divides, that DNA has to be copied. 0:21:07.800 --> 0:21:11.600 The copying mechanism is such that our chromosomes get slightly 0:21:11.680 --> 0:21:17.320 shorter every time the cell divides. Okay, and these ends 0:21:17.359 --> 0:21:22.200 have a special structure. Now, when they become too short, 0:21:22.280 --> 0:21:27.200 that structure unravels. When it unravels, the end of our 0:21:27.400 --> 0:21:31.200 chromosomes looks to the cell like a broken piece of DNA. 0:21:32.200 --> 0:21:37.840 That the cell has evolved mechanisms that if there's a 0:21:37.920 --> 0:21:40.840 DNA break, it will either try to repair it, or 0:21:40.840 --> 0:21:43.280 if it can't repair it, it will send the cell 0:21:43.320 --> 0:21:49.200 into Sinessence. Why, because a cell with a defective genome 0:21:50.240 --> 0:21:53.320 is at cancer risk because it's about you know, it 0:21:53.359 --> 0:21:56.760 could do all kinds of you know, abnormal things, and 0:21:56.840 --> 0:21:59.600 it's much better to send that cell off to sinessence 0:21:59.640 --> 0:22:04.280 and have it be removed by the immune system, then 0:22:04.359 --> 0:22:08.760 have it continue with a DNA defect or a chromosome defect. Right, 0:22:09.280 --> 0:22:13.520 So the cell has evolved as DNA response damage response 0:22:14.240 --> 0:22:16.840 in order to get rid of cells that are problematic 0:22:16.880 --> 0:22:20.600 in this way. But of course that same thing is 0:22:20.760 --> 0:22:25.800 causing senessens and increase in senescent cells as we get 0:22:25.840 --> 0:22:28.880 older and causing us to age. So that's a very 0:22:29.600 --> 0:22:34.679 you know, clear example of how something that may have 0:22:34.760 --> 0:22:39.159 evolved as an anti cancer mechanism early in life really 0:22:40.000 --> 0:22:42.399 is a cause of aging later in life. 0:22:42.480 --> 0:22:44.400 All Right, I want to hear a lot more about that, 0:22:44.440 --> 0:23:06.400 but first we have to take a break. Okay, we're 0:23:06.440 --> 0:23:08.440 back and we're talking about aging. 0:23:09.119 --> 0:23:11.560 So you mentioned that as cells go on and replicate 0:23:11.720 --> 0:23:15.520 the telomeres, you get shorter. But we and this is 0:23:15.560 --> 0:23:19.360 another listener question, but we're able to, you know, combine 0:23:19.359 --> 0:23:21.720 our gam meets with somebody else and make a fetus 0:23:21.720 --> 0:23:25.359 that has all new cells. And you also mentioned that starfish, 0:23:25.440 --> 0:23:28.679 can you regenerate an entire arm using stem cells? So 0:23:28.720 --> 0:23:31.600 why is it inevitable that our cells will break down 0:23:31.640 --> 0:23:34.120 when we seem able to set the clock back if 0:23:34.119 --> 0:23:35.640 we want to so we. 0:23:35.680 --> 0:23:39.919 Have evolved so that most of our cells have lost 0:23:39.960 --> 0:23:45.800 that ability to regenerate, probably because you don't want all 0:23:45.840 --> 0:23:48.240 of the trillions of cells in our body to be 0:23:48.280 --> 0:23:51.320 able to keep dividing at will, because that is also 0:23:51.359 --> 0:23:54.919 a cancer risk, okay, because they could acquire mutation and 0:23:54.960 --> 0:24:00.000 then they could become cancerous. So we have specialized cells 0:24:00.040 --> 0:24:06.720 called stem cells, which can keep regenerating. They don't go 0:24:06.760 --> 0:24:13.560 into senescence, and these specialized cells their role is to 0:24:13.720 --> 0:24:18.280 regenerate tissue. Now where do these stem cells come from, Well, 0:24:18.320 --> 0:24:21.200 they came from the fertilized egg. The fertilized egg is 0:24:21.240 --> 0:24:25.439