 And so now it's my additional pleasure to introduce my longtime colleague in the psychology department and probably the Gustavus' leading authority on the field of aging, Dr. Richard Martin here, who will introduce our first speaker. Thank you very much, Tim. I would also like to welcome you to the 40th annual conference, the Science of Aging. It promises to be a really special conference for me and I'm sure for all of you as well. I'm very pleased to introduce Dr. J. Oshansky because I admire his work so much. Dr. Oshansky received his PhD in sociology from the University of Chicago in 1984. He is currently a research professor in the School of Public Health at the University of Illinois at Chicago and a research associate at the Center of Aging at the University of Chicago and at the London School of Hygiene and Tropical Medicine. In addition, Dr. Oshansky is president of the Society for the Study of Social Biology and associate editor of the Journal of Gerontology and an editorial board member of other various scientific journals. Dr. Oshansky has played an essential role in the development of a new field called biodemography. This is a multidisciplinary approach that integrates our knowledge of biology with the knowledge of longevity and survival. To do this, he was a recipient of a Special Emphasis Research Career Award from the National Institute on Aging, which provided him the opportunity to gain additional training in the fields of evolutionary biology, molecular biology, and epidemiology, and later received a five-year Independent Scientist Award to conduct his research. He has written extensively on estimating the upper limits of longevity. These estimates have profound implications for social policy in an aging society such as ours. He has testified before the trustees of the Social Security Administration, where his research has influenced forecasts for our national entitlement programs. He is a clear and lucid writer and has repeatedly demonstrated an ability to think outside the box. He is internationally known and he has presented his research on longevity to groups around the world. Now, his writing on longevity could be described as cautious or even conservative, but he is something of a risk-taker. He has a bet of a half a billion dollars with Dr. Stephen Ostead, a biologist at the University of Idaho, on whether there is someone who is alive in the year 2000 that will be alive in the year 2150. Stephen Ostead has said yes. Dr. Oshansky has said no. I should probably hasten to add that the initial outlay for the bet was $150 each and it was invested and they figured that the interest compounded over 150 years would be $500 million, but still. Now, both of these men are absolutely convinced that the other is wrong and that they will win the bet, but they probably will never know. This bet is a bet that the descendants of Dr. Oshansky and Stephen Ostead will collect on. Interestingly, Dr. Oshansky told me that his own daughter is hoping Steve Ostead will win the bet. Now, although Dr. Oshansky has been strongly critical of anti-aging remedies, there is one practice of anti-aging that he believes in, engaging in his research. In a review of Lenny Garente's book on the Ageless Quest, he writes, Most scientists, as they themselves admit, are just big kids working on somewhat more complex questions than they faced when younger and all are driven by a childlike enthusiasm and excitement that is unparalleled in the working world. I invite you to listen, learn and enjoy. Please join me in welcoming Dr. Oshansky. Well, that was an absolutely wonderful introduction. Greatly appreciated. And I want to point out, I want to emphasize how much of an honor it is to be here. I'm absolutely delighted. I greatly appreciate the invitation from Dr. Peterson and Dr. Robinson. You have to realize for scientists to come to a place like this and to see the support 6,000 plus people interested in science discussing debating science, you have to realize how gratifying that is for scientists. This issue of aging and longevity is a fascinating one, particularly for those of us who are involved in various elements of it. And I anticipate that sometime in the near future, one or more of the pioneers in our field will indeed receive the Nobel Prize for gerontology for research on aging. I greatly look forward to that. Now before I get started, I really want to do something. You know, those of you who are in the field of psychology, psychotherapists know you need your patients as much as your patients need you. And I need my students as much as students might need their professors. So I really would greatly appreciate it if the student volunteers, I know you don't know about this, if the student volunteers would come up and sit right here. But as you have to realize, I can't see past more than just a couple of rows. So please, student volunteers, get up. You have to come over here and sit down in these seats and you are going to be the people whom I'm speaking to quite immediately. I hope you're able to see the screen. I greatly appreciate that. You can also do me a favor, by the way, by pouring me a glass of water. Thanks. Okay. Let's see. Let's get started. First of all, let me emphasize one thing. And the underlying philosophy, thank you very much. The underlying philosophy of my entire discussion today is going to be based on this sentence. And that is, for those of you who might not be able to read this or see this, this comes from Dubjanski from 1973 and says, nothing in biology makes sense except in the light of evolution. That is going to be the underlying theme of what I'm talking about today. Now, it's easy for those of us in this field to distill basic concepts in the field down to a few questions and we tend to do that. I certainly tend to do that as best as I can. So I've attempted to distill down the field of aging to three main questions, of course, many more than three main questions, but I will distill them down to these three. Why do we age? When do we age? And how do we age? Now, incidentally, I am going to provide answers to the first two of those questions. The third one, I don't believe anyone knows the answer to yet, but you're going to get some insights from the subsequent speakers. And the linkage between why and when we age will be fairly obvious. Now, since you're going to hear about aging and aging related issues for the next two days, it's important that we start out with terminology. I mean, we might as well get it right from the beginning. Let's use them right consistently throughout. We are going to be those of us who mix these terms throughout the entire meeting. That's inevitable, but let's get it right from the beginning. First of all, let's distinguish between aging and senescence. Aging should always be considered the passage of chronological time. So all of us age at exactly the same rate, but we can senesce or grow older biologically at different rates. You can have individuals who are all 60 years of age. Some can be much older biologically than others, and the term for that should be senescence. So it's important to distinguish between the passage of chronological time and the passage of biological time. And as a classic illustration of this, I have this wonderful image that comes from Scientific American of these identical twins who would appear to be senescing at quite different rates even though they are chronologically identical. I don't know if the one on the right, by the way, had plastic surgery or if she colored her hair, but I do know that the one on the left had Alzheimer's disease and the one on the right did not. At the time this picture was taken. Okay, life span. Life span should be defined as nothing more than the observed duration of life for an individual. So life span could range anywhere from moments after a live birth, just a few minutes, to 122 and a half years of age, which is the current world record for human longevity. That is the range of life span. There's a tendency to mix these terms up, but the life span should be used to define duration of life for an individual. Life expectancy is nothing more... Well, it's a bit more than this, but it should be considered essentially an average for a population. And this is the term that you'll see most often appear in the literature as life expectancy for a population. It is essentially an average age of death. It's not quite that, but it's close enough for our purposes. The important point to remember is that it's for a population. Maximum life span is the longest lived member of the species. It's the tip of the tail of the survival distribution. It's the world record. It's the Guinness World Record for longevity. For any species, in the case of humans, it's, as I said earlier, 122 and a half. And I'm actually going to show you a picture of the world record holder for human longevity. Now, let me first explain why it is that we live as long as we do. It's sort of one of the basic questions for those of us who study duration of life. And there's plenty of misinformation out there about why it is that life expectancy is as it is today and why we live as long as we do. And I actually have two very simple and straightforward images that will illustrate why it is that we live as long as we do. Some of this was discussed in an article that my colleagues and I published in 1993 called The Aging of the Human Species. And I always like to acknowledge my friends and colleagues with whom I work, Bruce Carnes, who is now at the University of Oklahoma, and Christine Castle, who was at the University of Chicago with me many years ago back in the early 90s. This is the simplest way of understanding, at least in part, why it is that we live as long as we do. It's important to realize that throughout most of human history, infectious and parasitic diseases were the major causes of death. In fact, the vast majority of all humans ever born died before the age of 10 from an infectious or parasitic disease. It's only in modern times that we get to see what we know of as aging, as much longer lives. And so what we had was very high birth rates and death rates, roughly 50 per thousand throughout most of human history. And in today's developed world, death rates began to decline very rapidly right around 1850 until they reached very low death rates as they exist today in developed countries of about 8 to 10 per thousand. And so it's this transformation within just 100 to 150 years that led to extremely rapid increases in life expectancy, rapid declines in death rates. And of course this difference between the birth rate and the death rate is why we have so many people on the planet today. This is perhaps the easiest explanation for why it is that we experience this quantum leap in life expectancy. Let me explain this figure. On the x-axis is age. On the y-axis is number of deaths. Now if you were to take a hypothetical group of 100,000 babies born in a giving year and you applied to those babies, the death rates observed in that giving year at all ages and you plotted out the ages at which all of those children had died, you would get something referred to as a distribution of death. That's what this is. This is a distribution of death for females in the United States in 1900 and in the year 2000. So the area under the curve is the same under both conditions. It's 100,000 hypothetical babies. Well this is a classic illustration of why we live as long as we do today. You can see in 1900 extremely high infant and child mortality before the age of 10. You see this characteristic hump in mortality in females right around the age of 20. Tell me why it is that you see that increase in mortality right around the age of 20 in females in 1900? Yes, exactly. Childbirth. Maternal mortality was very high at the beginning of the century. Absolutely. And once you made it past those first couple of decades of life, even in 1900 you had a reasonable chance of making it out past 70, 80, and 90. And we even know that there were a couple of instances of extremely long-lived individuals from a couple of thousand years ago. There's evidence to indicate that one of the pharaohs perhaps lived over 100. So we've always had the potential to live a long life. But what you see here is essentially a redistribution of death from the young to the old that occurred within an extraordinarily short time period. Within four human generations we have been able to transform death from something that occurred at younger ages and this is the distribution of death that we now see in today's developed world. And this is why we had the quantum leap in life expectancy, the 30-year increase in life expectancy during the 20th century. It's not because we have influenced aging in any way. Aging has never been influenced in humans in any way. In fact, you'll hear some discussion about this, but there appears to be no evidence that aging itself has been influenced in any species. By any intervention that currently exists. So what we see here in this particular figure is a transformation of life expectancy at birth. This was this term that I was using earlier from about 49 in 1900 to about 80 today here in the United States for females. The modal age of death has increased from 73 to 88. Maximum observed age of death has increased from 105 to about 113 and there's no evidence that more than one, perhaps two people on Earth have ever lived past the age of 120. I anticipate, by the way, that that world record will be broken in this century. If you just increase the number of individuals the size of the population, you tend to push out the tails of the distribution and I anticipate that world record will be broken. The question is, how interesting is it for the rest of us who have little or no chance of making it out to extreme old age? The answer, by the way, is I think for a number of reasons, it will be very interesting to study these centenarians, people who live past 100 and super centenarians, people who live past 110 and I'll talk about that a little bit later. So let's get to this question, why do we age? Well, I'm going to argue that humans are essentially this, a rather amazing, miraculous machine. This happens to be a Bentley, it's a very expensive, highly efficient car, it runs very well, that eventually turns into this. And that this line of reasoning, this transformation of this miraculous machine into what ultimately turns into, if you can't see this, is essentially a junkyard, for automobiles also applies to dogs. This happens to be my dog, Sophie. It applies to horses, it applies to mice, in fact it applies to most sexually reproducing species. So, why aren't we immortal? Why do we live as long as we do? That's the symbol of immortality, by the way. Well, there's another way of asking that question. Well, the question of course is why aren't we immortal? Why don't we live forever? Even though we know we're composed of particles that themselves are immortal. Well, the answer is fairly simple and straightforward. Of course, it is an oversimplification, but it is a fairly straightforward argument that comes right out of evolution biology. It's an argument that immortality, in a way, already exists. It exists for elements of DNA. And in fact, all of us in this room, all of you watching and listening, are carriers of DNA that has been around since the origin of life on Earth. And once DNA acquired the property of immortality, its carriers, you and I and other sexually reproducing species, became mortal. The evolutionary theory of senescence is perhaps the best explanation for this, and I'm not going to go into detail. I'm going to use a simple image to explain this, but I do want to mention the individuals, main individuals involved in developing the evolutionary theory of senescence, which of course began with Charles Darwin. Sir Peter Medowar in the middle part of the 20th century developed the notion of mutation accumulation, basically arguing that the post-reproductive region of the lifespan is essentially a genetic dustbin. There's no penalty for having genes that do bad things late in life as long as they do good things early in life. George Williams, who is still with us, developed the notion of antagonistic pleiotropy, genes that are harmful late, are selected for because they are favored early in life. That was his argument. And the disposable soma theory by my friend and colleague, Tom Kirkwood, who basically argues there's a limited amount of physiological resources and in a world where immortality is not biologically possible, it's much better to invest in reproduction than immortality. Well, here's my simple explanation of the evolutionary theory of senescence. And I use this race car analogy as the easiest way, I think, to illustrate this particular phenomenon. Those of you here, of course, from the states will recognize that there is a race that is run right near where we live in Chicago called the Indianapolis 500. And the individuals, the engineers who build these cars know what the duration of the race is. They know exactly how far it is that they have to get these automobiles to run in order to complete the race. In this case, it's 500 miles. If something happens to go wrong with these automobiles during the course of the race, they bring them back in. They fix whatever goes wrong with them and they will send them back out. What's interesting though is that after the end of the race, they turn the engine off. They bring them in and they replace many of the individual components of the automobile. But if you were to conduct an experiment on Indianapolis 500 race cars or perhaps your own automobiles and run them beyond essentially the end of the race, you would get to see things go wrong with these automobiles that you would never ordinarily have an opportunity to see. You would see things fall off, they would start to fall apart, they would begin to fail. And actually, if you look at the distribution of failure times or the distribution of death times for automobiles that are run beyond the end of the race, it would look nearly identical to that of living things. It's not actually surprising for those of us who study aging, but in fact aging or senescence is occurring among essentially everything. The important point to remember here is that the engineers who built these cars did not build them to fail. They didn't put in an aging program. What they put in was a program designed to make it at least a given distance. And what happens here is simply an accident of using these automobiles beyond the time in which, or in this case, the distance in which they were intended to be used. Now, you can apply the same line of reasoning to sexually reproducing species such as humans. Here, of course, in this particular case, the argument is that the end of the race is not a measure of distance, it is a measure of time. And time is defined by reproductive success. Reproductive success is defined by when reproduction begins puberty and when it ends menopause, of course defined by females. Now, essentially what we have done during the course of the 20th century, as I said earlier, is redistributed death from the young to the old. So we've conducted this grand biological experiment on ourselves that I'm suggesting could be done hypothetically with these automobiles. We are pushing individuals into the post reproductive region of the lifespan for the first time in human history with great frequency at a level that we have never seen before. And so what happens, we get to see senescence. We get to see aging really for the first time. And in fact, we only see aging and senescence as we see it in us in only a couple of other species. The animals that we protect are pets and laboratory and zoo animals. Very few, in very few cases, are you actually able to see senescence and when you do see it, it is nearly identical in all of those species, the kinds of things that go wrong. The same line of reasoning applies here that applies to the automobile. We are not... Essentially, we are conducting this grand experiment by pushing ourselves into the post reproductive period, but it's important to remember that there isn't a program for aging and there isn't a program for death. What we have are genetic programs for growth, development, and reproduction. And we get to see senescence by living beyond the time period when our bodies were essentially using quotes designed to operate. Now, this is a classic illustration of this particular phenomenon in the case of humans. This is age on the x-axis. This is, in this case, cumulative reproductive success and effectiveness of natural selection. I don't want to go into great detail on this. I just want to illustrate that the way in which I tend to look at duration of life in sexually reproducing species is to divide the lifespan into three regions. The pre-reproductive region, the reproductive region, and the post-reproductive region of the lifespan. In fact, that's how evolutionary biologists tend to look at duration of life. As soon as reproduction begins, right around the age of 13 to 15 in humans, the ability of natural selection to influence gene frequencies in subsequent generations decline rapidly. So, in the pre-reproductive period, if things begin to go wrong, particularly as a result of single gene lethal diseases expressing themselves, natural selection is very effective in eliminating those individuals from the population. They're not passing their genes on to the next generation. As soon as reproduction begins, the force of natural selection declines until we reach the post-reproductive region of the lifespan where the force of natural selection is at or near zero and where it is no longer possible to lead to the evolution of either aging or death genes. So there is a remarkable consistency to the timing of death across species that is directly associated with this linkage between reproduction and senescence. In fact, research that my colleagues and I have done, this is what we published back in the late 90s, demonstrated that the duration of life of species, and I'm going to repeat this because it's important, the duration of life of species in general is calibrated to the onset and length of a species-reproductive window. So the timing with which puberty occurs and the duration of this reproductive window influences ultimately the duration of life of a species. Here's a classic illustration. The mouse, for example, lives 1,000 days. The dog, on average, lives about 5,000 days. An elephant lives about 26,000 days. A human, on average, lives about 29,000 days. I do present this in days for a very specific reason, which will be obvious perhaps later. Sea turtles live about 55,000 days and bowhead whales live about 77,000 days. It's absolutely amazing when you look at this and you look at the timing with which reproduction occurs. We know when reproduction is occurring in a mouse. It's fairly shortly after birth. I think it's within about 30 days. The sea turtle is not even capable, it doesn't even go through puberty until 50 years of age. It is capable of reproducing for 100 years and it lives about 150 years. The important message here is that there is a fundamental biological link between when reproduction occurs and duration of life, when senescence ultimately occurs in the species. We would argue, my colleagues and I have argued, that aging or senescence is, in fact, an accident of surviving beyond what we refer to as the warranty period for living machines. You know this already. If you trade your car in every two to three years, you're not going to see too many things go wrong with your automobile, but if you operate your car for seven, eight, nine, ten years or longer, you push it out to two, three, four hundred thousand miles, you are going to see things go wrong with that car that you never would have had an opportunity to see and the same thing applies to our bodies. If we push out the envelope of human survival further and further into the post reproductive region of the lifespan, it should be no surprise that we are going to see things go wrong with our bodies, that we have never had an opportunity to see before and the further out we push that envelope of human survival, the more things we are going to see go wrong. There's another way, and in my opinion, important way of illustrating this point and I use Linnaeus' description of the binomial system of nomenclature, he's the father of taxonomy, as a way to illustrate this particular point, this of course should be considered the tree of life. I just noticed I don't see any humans up here, but we're up there with all the other vertebrates just for your information. And this is the way I have illustrated this particular point. My colleagues and I have hypothetically created this place called Linnaeus Park. If you were to create some sort of park that we could all go to and visit and visit the genetic structure of every form of life that ever existed on Earth, and you could walk through this park. This park, I have it in this particular shape to resemble the tree of life essentially. You would see something that looked like this. The microorganisms would be down here at the bottom, the dinosaurs would be somewhere there in the middle, and mammals would be very recent development in the history of life on Earth. We're among those mammals. And I thought I'd put this on here. For those of you who are able to see this, this actually came from Linnaeus's classification, 9th edition, his description of... First description of humans was Homo diurnus, or Man of the Day. Now, here we are walking through Linnaeus Park, and we come upon the mammals, and the mammals that we see, including among them are humans. This is an image, I will tell you, that came from an article that my colleagues and I published in 1998 in American Scientists, and the description required for it was so complicated that we decided not to publish it. But it's a wonderful way to illustrate an extremely important point that I think will be discussed throughout this particular conference, and that's the difference between aging and disease. What you see here as you walk through Linnaeus Park are these statues representing every species. And this, for example, is the statue, of course, for the elephant, for the dog, for the mouse. And here we are at the statue for humans. And this, of course, is intended to represent a granite statue, and etched upon the statue is the DNA, the code of life for the species. And the code for life for the species is characterized principally by its effect on growth, development, reproduction, and the passing of the genes on to the next generation. What you see as a result of this particular genetic program for growth, development, and reproduction is something that we refer to as the shadow of senescence, or the shadow of aging. We would argue that we were essentially designed, and I always use that word designed in quotes, essentially designed for short-term use. Of course, mice were shorter-term use and bowhead whales were a bit longer. Humans, about 29,000 days, were essentially designed for short-term use. And that what you see in the way of aging or senescence is not a product of a program for aging or senescence. It is an inadvertent byproduct of genetic programs for something else, for growth, development, and reproduction. And we are very good. We have become very efficient at modifying the manifestations of aging or the shadow of senescence through our ability to treat the diseases of aging, like heart disease, cancer, and stroke. We're very effective at extending the duration of life of many of these individuals through chemotherapy, through, in the case of cancer, radiation therapy. Ultimately, genetics will allow us to influence other diseases through surgical procedures. There are many things that we can do to influence the shadow of senescence. But when we influence the shadow of senescence, we are not influencing the underlying biology that leads to aging itself. And it is critically important to distinguish between this phenomenon of the basic biology of aging itself and its shadow. And I'm not the first to make this argument. One of the pioneers you're going to hear later today, Leonard Hayflick, has been making this argument for decades. Very few people have heard this argument, and those many of whom have heard it have not understood it. And I hope Len spends more time talking about this later today because it's critically important to distinguish between aging and disease. So, is there a metronome for life? This comes up repeatedly. For those of you who might not be able to see it, that's a metronome. Is there a metronome for life? It's not strategically located, by the way. Actually, now that I look at it, I didn't realize what I did. So, is there a metronome for life, or is there a clock for aging? And the answer is no. There is a clock. There is a metronome for growth, development, and reproduction. And what we see as aging or senescence is an inadvertent byproduct of that. Incidentally, there are important implications of this because if indeed we are going to achieve some sort of dramatic extension of human life, it's not going to be a result of modifying the shadow of senescence. It's going to have to come from modifying the bedrock. And if you do that, what else are you going to be modifying in all likelihood? Any ideas? Basic attributes of growth, development, and reproduction. If we try to extend duration of life by modifying genes in all likelihood, we will see some basic change in other biological attributes of the species that we may not like. So, is there a genetic program for aging or death? The answer would be no. And I actually have these props that I use. I can't actually carry these with me everywhere that I go, and I have these two wonderful coins that I carry. One is this Morgan dollar that many of you are familiar with. This one on the right, not by coincidence, was minted in 1882 and is 122 years old. This will outlive everyone in the room, this particular coin. And actually, this coin, which is the one on the left, is 2,000 years old. This one outlived the vast majority of all the humans that have ever existed. It's about 2,000 years old. Here I'll give these to you guys to look at. As a way to illustrate that aging occurs in a wide variety of living and non-living things, not because that there's a program, not because there's a program. And it's particularly important to emphasize that you're going to see senescence occurring in a wide variety of things in the absence of a genetic program for aging or death. And of course, there are classic illustrations of this. These are coins that would, these happen to be made out of chocolate. They would last only minutes. Here is money. And my wife's hands would also last only minutes, but she's here, by the way. These, the paper money will last for, I know I'm going to pay the price for that. Paper money would last for years. Wooden money would last for decades. And money made out of metal will last much longer. So indeed, duration of existence is fundamentally influenced by the physical properties with which things are made. Now I'm going to shift gears here for a moment to look at the picture of death. And I do this for a very specific reason. It's a very good way of illustrating the timing with which death occurs. Now as it turns out, a famous statistician by the name of Carl Pearson in the latter part of the 19th century commissioned an artist he wanted to illustrate the timing with which death occurs, not just in humans, but actually ultimately in other sexually reproducing species. And this is a wonderful illustration. It's referred to as the bridge of life, but of course it looks like anything but the bridge of life. What you will recognize here is these particular skeletons represent what we refer to as the force of mortality, where the ability of death to harvest individuals at various ages. And it's a classic illustration of the timing with which death occurs. You can see that Pearson knew back in the late 19th century that infant mortality was extremely high. And this is illustrated by the force of mortality about to bash this infant over the head, indicating extraordinarily high infant mortality. You can see the force of mortality using a gatling gun here to take out children, also indicating extraordinarily high death among children before the age of 10. The point of lowest mortality where death harvests its fewest individuals is always at puberty where the price to be paid for harvesting individuals is greatest from an evolutionary perspective. This is indicated by the use of a bow and arrow. A musket takes out individuals at middle life and a rifle takes out individuals at older ages indicating a much more accurate way of removing individuals from the population. Now there's some subtle messages in this particular image that I really want to emphasize here. First of all, I want you to notice well, actually I have my students right up in the front here. Are there any subtle messages that you might notice of this bridge of life? That's right. There is no crossing over in this particular case at least in the physical body of this particular physical body making it to the other side. And so Pearson was basically arguing back and what he believed in the latter part of the 19th century and that is that there's a biological limit to the duration of life. That was what he believed and others believed was that there was some sort of biological limit. Now there were a couple of other subtle messages that I always ask my students about and one is take a look at the force of mortality here at these younger ages. The force of mortality has its eye on its target in every case here except one. And I want you to tell me why that is. Why is the force of mortality not even looking at its target? Well, okay the comment was it's a sure shot and actually you're you're right you're absolutely right. Actually what Pearson was thinking at the time was you know I don't really need to take out these individuals with my rifle. I could do it very easily and I do it all the time with heart disease, cancer and stroke but I don't have to because those individuals are going to die anyway from senescence, from aging. It was a basic, it was a classic illustration of an argument that I think we've been trying to make for a long time is the distinction between aging and disease and there's one other subtle image that I think Pearson was trying to get across here if you notice these individuals at younger ages are looking forward and even this older individual is looking forward but why is this individual here in middle age not looking at the other end of the bridge but looking towards the force of mortality. Can somebody now actually I don't know if you guys are old enough to know the answer to this question but any guesses? It's not programmed? No? Any other ideas? What Pearson was trying to do with this particular image was he was trying to recognize that once you make it to middle age, whatever that might have been I don't know what he defined middle age this might be a good question for somebody to ask later what he defined as middle age you begin to recognize your own mortality and I think that's exactly the image and the message that Pearson was trying to get across with this particular image this is what death looks like for humans and actually for other sexually reproducing species this is age on the x-axis this is the death rate on a semi-log scale on the y-axis indicating very high infant mortality you can see the death rate declining to its lowest point at puberty and then it rises exponentially thereafter this is a character what's referred to as a J-curve or a characteristic mortality schedule and you see it among most forms of life here it is illustrated for mice, for dogs, for humans this was work that my colleagues and I published back in the late 90s indicating that once you compare sexually reproducing species on the same time scale you stretch out that duration of life that 5,000 days for the dog and you put them on a comparable time scale you actually discover that the timing with which death occurs is virtually identical for sexually reproducing species and that's what we've illustrated here is that the death rate rises exponentially in the same rate for a wide variety of species next, longevity revolution where are we headed in the future what might lead to the next longevity revolution well there are a couple of books there are many books that have been published on this topic one of my favorites was from a friend and colleague by the name of Greg Stock who wrote what I consider to be a very good book called redesigning humans a fascinating set of arguments a number of other books have been published on this particular topic and this is in part the line of reasoning used by some for how it is that we're going to achieve another quantum leap in life expectancy and that is to essentially and this is already happening of course replacing body parts and we become very good at replacing body parts here of course is a replacement of the hip of the knee corneal transplants this is one I haven't bothered with yet but this is a hair transplant I never will bother with this one we've been able to replace our teeth and ultimately we can replace many of the organs inside the body the lungs the liver parts of bones skin, kidney, pancreas heart and valve and actually we become very good at replacing body parts and we're getting better at it but the problem is that you can't replace everything and one of the things that we simply cannot influence significantly at this time hopefully we will be able to influence at some time in the future is the brain itself and so remember if you're able to replace all of the body parts in one way or another but you can't replace the brain what have you done you've created a potentially very dangerous scenario where you have a healthy or well functioning body but a mind that is deteriorating very rapidly and anyone who knows individuals who have had Alzheimer's disease dementia recognize that this is not a good combination there are also arguments that efforts are going to be underway to modify the underlying biology of humans through a number of other ways through sex and trait selection which is already possible through human cloning which is close to being possible through germline modification and last but not least for those who are unable to read this this is a it says right up here genetic engineering to eliminate disease modify physiology and morphology and combat aging it's a picture of a tuna that has been genetically modified and it says we've genetically engineered a tuna exactly the same diameter as our cans now I put this up here for a very specific reason and that is to make you aware of the fact that that the language of improving the human species is a language that has been with us since Darwin and in fact it led to what I considered to be an extraordinarily dangerous it led to an extraordinarily dangerous phenomenon of a discussion of positive eugenics and negative eugenics at the beginning of the 20th century and the language of the eugenics movement at the beginning of the 20th century was actually it was initiated in many cases by scientists and it was initiated for the purpose of improving quote unquote improving humanity and I dare say that we are very close to using in fact not just very close we are already beginning to use the same language that was associated with the positive and the negative eugenics movement at the beginning of the 20th century arguing that we are on the verge of modifying the basic biology of our own species in order to quote unquote improve it and there are inherent dangers associated with the language of the eugenics movement both then and today and I think we need to be extraordinarily careful and cautious about efforts to modify the underlying genetics of our own species you realize of course is that there will be I have no doubt wonderful advances in technology that will occur as a result of genetics stem cell technology and genetic engineering I have no doubt that this is going to happen and we will wipe out I suspect many diseases but there will be an effort in my view to cleanse the human genome of diseases and disorders and things that we don't like and of course as soon as you identify genes that we deem to be undesirable you then have to identify the individuals who possess those genes and you move down that slippery slope that we faced more than 100 years ago and I am personally quite concerned about that particular issue now on a lighter note I would ask the question what if we could in fact redesign the human body now I will tell you that my colleagues and I have worked on this particular issue for the last few years asking a very specific question what if indeed mother nature operated with an open eye rather than a closed eye and what if mother nature could could essentially design a human body built to last longer than the one that we currently have I will tell you my colleagues and I had more fun and enjoyment drafting this particular manuscript that was published in Scientific American it was republished last summer in this issue on human evolution we had more fun writing this article than any other article that we had ever written and science should be fun it should be enjoyable what we did essentially we stood it up and we asked the question body part by body part how could we do it better because we know what it is that fails in the human body with the passage of time if we could design body parts better than they are currently designed how might this entire body look if we could do it better than is currently the case I will tell you that we did all of this back in about 3-4 years ago and we have a new manuscript called Human Body Design that is forthcoming in American scientists where we go inside the body and make a series of changes at the molecular level to illustrate a particular point let me show you what we did here two views of human body design one is that of Michelangelo of creation exemplifying essentially the perfection of humanity that the human body in the image of God is indeed a perfect physical specimen that is one particular image that you will see and hear often and the other of course is that of Charles Darwin suggesting that there were a number of anatomical oddities that exist in the human body and that he presented that ultimately as the strongest evidence for his theory of evolution illustrating a couple of examples of organs in the body that perhaps don't really serve very useful functions in this particular case the appendix the knee wasn't particularly well designed the hip wasn't particularly well designed most of the people in the audience are going to know that these are some of the major problems and my favorite I think it's a classic illustration and that is this I'm turning to the side here to illustrate my Adam's apple here there's rather bizarre contraption in the back of the throat called the epiglottis which if you were to design it you would think to cross the food in the air passageway in the back of the throat it makes no sense and the heavy price we pay for that crossing of the food in the air passageway often is choking very bad design well as it turns out the view that we present in our manuscript is that indeed both Michelangelo and Darwin were right the human body is indeed and should be considered a miraculous living machine works with near artistic perfection it's actually amazing we live as long as we do given the toxic soup that's produced by our own the cellular machinery of life it's amazing that we actually live as long as we do but time in fact reveals what we refer to as the flaws in body design a body that was not intended for long term use and that we indeed are pushing well beyond the end of its biological warranty period so here's the argument that we made with our colleagues Bruce Kearns again from Oklahoma and this article was also co-authored by Bob Butler from the International Longevity Center in New York Bob was also the founding director of the National Institute on Aging alright here's what we did we started out with with this rather bizarre contraption of what is in this particular case obvious bipedal locomotion and you don't really see this elsewhere in the animal world you'll see it for moments at a time in other species and I'm sure that there were wonderful benefits associated with bipedal locomotion for our early ancestors it certainly freed up our hands to do other things but we paid a very heavy price for walking upright and walking upright bipedal locomotion as it turns out is a disaster when you do it for 7, 8, 9, 10 decades it's great for the first few decades but when you do it for a long time period a number of things go wrong many of us are familiar with the kinds of things that go wrong including problems with this joint right here this particular hinge really was not designed to operate that long this particular hinge right here was not designed to operate as long as we tend to use it these pulleys I use the analogy pulleys, pumps, levers and hinges because essentially when you look at the body that's what it is these particular pulleys these muscles begin to atrophy with time bone density we lose bone mass right around the age of 30 in humans and there are a number of problems all the way up and down that are associated with bipedal locomotion and then of course there are a number of other problems that occur with the passage of time including sensory impairments loss of hearing we actually proposed some modifications to these and I'm going to show them to you one at a time and I will tell you that when we proposed these to begin with we had no idea what this anatomically modified human was going to look like we sent all the information to an artist and we had the artist recreate the human for us and then they essentially showed us what it was going to look like so here's a classic example I'm only going to give you a couple of these a couple of classic examples the problem with the epiglottis problems with the eye it's amazing that the eye actually works at all considering the number of things that go wrong with it with the passage of time well here are some of the changes that we made one of the first things is we increased the size of the outer ear and we made it mobile and that's what I do all the time when I can't hear something I go like this so I can collect sound more efficiently so we essentially increased the size of the outer ear the artist by the way called me up and said what do you want it to look like I said well I'm a fan of Star Trek why don't you make it look like Spock ears we also increased the number and durability of the hair cells in the inner ear because ultimately that's one of the reasons why we begin to lose hearing with the passage of time those of you who like to listen to loud rock music you begin losing those hair cells it's ironic my kids will go to those rock concerts and they'll listen they'll stand right next to the speakers and I'll tell my son you know you're gonna start to lose your hearing and he just completely ignores me of course we chose and a lot of people completely ignore that advice by the way and of course that's precisely why we have some of these problems as we grow older with loss of hearing we have a number of problems associated with the eyes all we did was we simply used the more stable connection of the retina to the back of the eye that exists in the case of a squid the squid appears to have a better attachment than we have so we simply adopted the squids attachment as a way to illustrate that perhaps the eye could have been designed differently this is my favorite for any male over the age of 50 and I turn 50 in February you know what I'm talking about here and I will tell you that my father is 89 years old he's still plumbing and I went to him for advice when it came to this particular organ in the body the prostate and I said what do you think dad and he said he said Jay this is the work of an apprentice who would think to run a tube carrying a liquid through an enclosing organ it makes absolutely no sense whatsoever it works well for a while 4, 5, 6 decades for some people after a while it just simply begins to fail most of us are aware of this problem at later ages and so our fix was simple we moved the urethra or we moved the prostate I don't know which one we did anyway we pieced all of these together and to make a long story short this is what we came up with we shortened this animal down to about 5 feet or less and we did it for a very specific reason to lower the center of gravity to reduce the probability of falling which is a major problem for individuals who ultimately have hip fractures the other thing we did was we increased bone mass in this individual so that they would have more bone to lose once it begins demineralizing around the age of 30 we increased the padding of the joints I reversed the knee joint not as a way to illustrate what we have but as a way to illustrate the one that we have really doesn't work that well we increased bone muscle mass we tilted the upper torso forward 15 to 20 degrees in order to lessen pressure on the lower back ultimately some bio engineers came up to us and said well Jay that would actually have the opposite effect and they were right of course and then because my father was a plumber we added in check valves, more check valves in the lower extremities to make sure that blood would be moving more efficiently to the upper end of the body here's the male version of the same thing and our bio engineer friends pointed out to us that if you tilt the upper torso forward 15 to 20 degrees you reverse the knee joint and you put any weight in this hand what's going to happen that's right it's going to fall right over and I pointed out I said you know that's what you think this is all about you missed the point the point is not that we were trying as scientists to come up with a better design we were not as scientists trying to suggest this is what we should be pursuing we were not as scientists trying to suggest that we should be attempting to genetically modify humans in order to make us look like this or act like this in any way we were doing this for one reason principally and that was to illustrate that the body design that we do have that is currently unchangeable was not intended for long term use here are some of the images that appeared in the newspapers after that article was published this one was in San Francisco this came out in the Singapore Times within about a week after the article was published it created a supermodel they had to have a female version of the same thing now I will tell you that in our latest manuscript and I am very pleased to say that Len Hayflick has agreed to contribute to this particular manuscript and our other colleagues are Michael Kahn Michael Bemben and Deborah Bemben and my colleague Jacob Brody and this article you will see later on I think it's going to be published in January or February in American scientists and we will give you a taste of what we fixed I know you will be pleased to hear that in this manuscript we fixed all of these problems we fixed obesity we fixed osteoporosis we fixed hearing loss we fixed atherosclerosis we fixed sarcopenia I know others will be pleased to hear we fixed Alzheimer's disease what that fix is and last but not least I am pleased to say that Dr. Hayflick was kind enough to fix aging now as it turns out you will realize that we didn't really fix anything what we were really trying to do is stimulate more research in the field of aging to go after these kinds of problems what about pursuing life extension in humans well look at this we know we have the evidence before us we have all of these species the mouse, the dog, the human the bow head whale clearly they are shaped differently but there are fundamental attributes of each of these species that are identical I mean we breathe we have blood flowing through our bodies, we have bones we have red blood cells and white blood cells and yet you have one species that lives 77 times longer the bow head whale lives 77 times longer than the mouse and so there is something underlying the duration of life of these species that we need to discover as scientists and I think scientists need to be pursuing and indeed are pursuing these fundamental differences in longevity between species as a way to find perhaps why it is that we live exactly as we do and perhaps find a way of intervening the duration of life actually there was a point I was trying to make there well actually I already made it so pursuing life extension in humans of course we have a classic illustration in our own species individuals who make it up to 120 and individuals who die in their 20s, 30s and 40s we see it within our own species great variation and perhaps we need to begin discovering why there is such great variation in duration of life in humans and let me point very quickly to a project that actually is being initiated by a colleague who is somewhere here in the audience a fellow by the name of Dan Butner a project called LifeQuest which is an effort to essentially go across the globe identify sentinarians particularly super sentinarians people who live past 110 and try and not just discover what it is about their lifestyles that might be influencing how long they live and how healthy they are but the genetics of exceptional longevity and ultimately I believe we will be traveling to these various places to evaluate the sentinarians and super sentinarians in these various parts of the world Dan happens to be from right here in Minnesota wonderful project that hopefully will take off in the coming years I'm right near the end can we slow aging now as it turns out for the first time scientists can now say we have extended experimentally the duration of life of a wide variety of things we've done this it's been done and Cynthia Kenyon is going to talk about this tomorrow it's been done in worms that's a fruit fly by the way reading a newspaper it's been done in mice it's been done in a wide variety of animals and in fact we can extend the duration of life of humans I mean you can do it by wearing your seat belt and in fact we're very successful at extending the duration of life of humans but the question is is there any evidence to indicate that the biological process of aging has ever been modified in any species whether it's a nematode, a fruit fly, a mouse a human whatever and we would suggest many of my colleagues and I would suggest that there's no evidence that aging the basic biological process of aging itself has ever been modified but duration of life has I'm going to skip over that and I'm going to end let me see if this is quite near where I'm at at the end oh this question was asked of me by a reporter not long ago and I've heard it many times and that is who cares how we extend duration of life if we extend duration of life by altering the risk of disease by altering heart disease or cancer what difference does it make as long as we can make people live longer why should anyone care whether life extension occurs by slowing aging or modifying the risk of fatal diseases and I would say emphatically we should care it's extremely important to know the difference and understand the difference between modifying the manifestations of aging which is what we are very successful at doing now and modifying the biological process of aging itself and this is the figure I'm going to use to illustrate why this is so important you remember that distribution of death I showed you earlier in the presentation this is a truncated version looking only at ages 50 to 120 and it's a classic illustration of the potential problem we may be facing if we continue to combat only the fatal diseases the manifestations of aging such as heart disease, cancer and stroke what we have essentially done during the course of the 20th century as a result of redistributing death from the young to the old is we've pushed out survival into older and older regions of the lifespan where individuals face elevated risks of a wide variety of non-fatal diseases and disorders arthritis, osteoporosis, vision hearing impairment and other diseases and disorders that are expressed at an increasing rate at later and later ages so if we push out the envelope of human survival only by influencing its manifestations there is a very real possibility that we may in the end be extending the period of frailty and disability at older ages this was referred to many years ago by I think it was Ernest Greenberg called the failures of success extending the duration of life and of course there is a benefit to extending duration of life for those at middle ages but remember when we add when we add time to life through medical technology when we add time to life through our exercise programs ultimately it's always at the end we're not adding it at the beginning we're not adding it at the middle it is always at the end and so while you may in fact be healthier when you are younger and middle ages and of course that's the reason why many of us exercise so we can feel better now ultimately we may pay the price by extending duration of life in these older regions of the lifespan where frailty and disability are higher so we have to be careful what we wish for we don't necessarily want to live that much longer if indeed we know it's going to result in increased frailty and disability however if we can extend duration of life by slowing the biological process of aging itself then frailty and disability simultaneously will be pushed out to later and later ages health extension in my view must occur simultaneously for both body and mind and any intervention that extends the duration of life of the physical body without simultaneously extending the functioning of the mind in my view would be a harmful intervention and I'm going to end with just a couple of this one cartoon and a couple of pictures this is a for those who can't see this it's two men sitting at a bench says my goal is to die before there's a technology breakthrough that forces me to live to 130 as a way to illustrate that you may not want to make it that long but I'm just wondering some of the things that go wrong and here are some of the examples of documented super centenarians people who live past 110 I don't know the names of these two individuals but this is the world record holder this is Jean Calmon who lived for 122 and a half years I will say that the last seven or eight years of her life she couldn't see, she couldn't hear, she couldn't taste she was immobile, she was incontinent she was working fairly well but she did have a wide variety of other problems here are some images pictures that I took when I was in Hainan, China of alleged centenarians and super centenarians we don't know yet whether or not it's true in Hainan but I just thought I would show you a couple of pictures of these very happy individuals in Hainan China I don't know how long this fellow was smoking this was allegedly the longest lived member of the population of Hainan she was said to be 110 and I would emphasize one particular important point here with this lady up here and I would emphasize that a day in the life of this woman who was allegedly 110 is in my view equally important as a day in the life of a child who is 10 years old and there's a tendency to discount the lives of individuals because they have lived longer lives and this is a lesson I learned from my professor Bernice Newgard many years ago and that is to emphasize the importance of life at any time at any age whether you're older or young and she deserves to live and enjoy her time and her day today as much as any of the rest of us and I will end with I couldn't resist I have to say this these are my last pictures this is a picture of a young lady who was actually sitting in the front row happens to be my wife she was I think about 10 years old when this picture was taken and I would say that sometimes many times often times aging can in fact be a very good thing to this this is my daughter on the right side she is now 20 years old here is Sarah today and her 50th birthday was yesterday so help me in wishing Sarah a happy birthday