You Are Getting Older (Part 1)

[00:00:01.84] DEBORAH ROACH: Hello.

[00:00:02.72] AUDIENCE: Hello.

[00:00:03.10] AUDIENCE: Hello.

[00:00:03.49] AUDIENCE: Hello.

[00:00:04.57] DEBORAH ROACH: I'm Deborah Roach. And I hope that you all are here to talk about the uplifting story about aging.

[00:00:13.79] [LAUGHTER]

[00:00:14.94] AUDIENCE: Old age.

[00:00:17.19] DEBORAH ROACH: And so I am fairly freshly retired only about a year and a half ago now from the Department of Biology. And while I was in biology, I actually taught a course on the biology of aging for about 25 years. And so I've gotten to know a lot about the field. But when I think about the field of biology, the biology of aging, I have to tell you that I don't just think about humans.

[00:00:54.82] I also think about plants. And I think about other animals as well. And so as we go through and talk about aging, I'm actually going to throw in some examples from other species too. But, of course, the focus for today and for the next week is really to talk about human biology of aging, and what we can do about it, how we can look at some of the myths that are out there and know what works, and what really doesn't work, OK?

[00:01:29.99] I have to say, first of all, that I said I taught this class for a long time. But I was talking to 18 and 20-year-olds. And it's different when you want-- I start the class out. And I always say, well, what's aging? And they look at me. And they talk about the cells and the sort of thing. And they had no idea. And so this is a really different audience for me to talk to. And it really makes it-- it's kind of fun.

[00:02:01.05] So I think all of us have a sense of what aging is all about. And so please, as we go through this, ask questions, OK? I'm sure you've wondered, what's this seminar going to be about? So what is this I've been thinking about experiencing over the years? So please don't hesitate to ask questions. And for people online, I'd also say welcome. And please write questions in to Kelly. And Kelly, just go ahead and raise your hand when someone else has raised a question. And is everything, before we go on any further, is everything OK online? So we're all set?

[00:02:47.03] AUDIENCE: Yes, thank you.

[00:02:49.06] DEBORAH ROACH: Yeah, OK.

[00:02:50.24] AUDIENCE: Maybe you let us know where they're going to pan the audience.

[00:02:52.74] [LAUGHTER]

[00:02:55.79] DEBORAH ROACH: OK. So when we think about aging, it's, of course, as the population has aged, and so forth, there are just many, many more books and myths, and there's so much out there that's really been thrown at us. And as a professional in the field also, I've always been surprised at how captured people feel, and militant almost, about what their research is about and how what they're doing is going to solve the problem.

[00:03:39.51] And so I go to meetings and so forth. And you see people living, their research, people working on caloric restriction or are eating very little at lunchtime during the breaks, and that sort of thing. And so it's really very interesting to think about all the ideas that people have about aging. And I guess what I'd like to say is the big take-home message is that aging is complex. And there is no one answer. So that will be the take-home message.

[00:04:22.74] But there's also an optimistic message that I hope you all walk away with. And that is this idea that, in fact, we can do something. We can actually look at biological processes and see that we can reverse this process, or increase our defenses against this process. And so that's where we're headed. And that's what I hope that you'll start to understand as we move forward.

[00:04:49.64] So today, what I'm going to do is I'm going to talk a little bit about lifespan, and then move into defining exactly what aging is all about. And then what I want to do is I actually want to then tackle one of the myths. And the myth that we're aiming for here is this idea that social interactions like these, the retired faculty association, actually can have an impact on biological aging. And I'm getting way ahead of myself. But I just want you to know where we're headed.

[00:05:30.67] And so let me get started. And I cannot start a-- I can't start a discussion about aging without talking about the two people, male and female, who have lived the longest. And this is Madame Calment, who lived for 122 years, and Mr. Kimura, who lived 116 years. And we all want to look at these individuals and say, wow, how do these people live this long? And what were their secrets?

[00:06:18.73] And I have to tell you that there's been a lot more research done on Madame Calment. In fact, there's been a book written about her. And some of the secrets as people talk about it from her are that she ate pounds of chocolate.

[00:06:37.60] [LAUGHTER]

[00:06:42.28] She drank red wine regularly. And the other thing is she rode a bicycle until she was 100.

[00:06:50.41] AUDIENCE: [INAUDIBLE]

[00:06:51.22] DEBORAH ROACH: And, yeah, seriously. And she lived independently until she was 110.

[00:06:56.65] AUDIENCE: [INAUDIBLE]

[00:06:57.88] DEBORAH ROACH: Yeah. So, I mean, this is someone we would call a super ager, because it wasn't-- she was living long. But she was also healthy. And I have to tell you that in my professional network, I knew someone who interviewed her. And he would interview her every couple of years to get information, see how she was doing, take all these health measurements. And one time when he was there, and he was in his mid-sixties, and he was finished his analysis and so forth, and was about to leave, and he turned and said, see you next year. And she said, yeah, you don't look so bad.

[00:07:42.73] [LAUGHTER]

[00:07:45.04] Saying that. Well, she, at that time, she was 117. So another take-home message from this is a sense of humor is actually a really good characteristic. And maybe it had something to do with this fact that she was a super ager. I don't know. But what I can tell you is that there's a lot of research going on looking at these people who are living to late ages, and trying to understand what their characteristics are, do they have unique genetics? Do they have innate behaviors? Do they have different unique environments, diets, and that sort of thing, to try to put all these things together? And there is a lot of research that's going on with respect to that.

[00:08:35.44] And there was something that I read about just recently, which suggests that when we think about the-- very often, you think, well, people who have genes that are going to predispose them to a high chance of getting Alzheimer's disease, for example. Well, it turns out, the expectation is that those people will have shorter lifespans. Well, it turns out that there's now a lot of good evidence that, in fact, some of these people who are living to these late ages and are healthy are also carriers of some of these genetic age-related diseases. Wow.

[00:09:24.58] And so the question then is, do they have other parts of their genome which are actually counteracting their susceptibility to these diseases? Or in fact-- or is there something about their environment that actually is limiting the expression of these deleterious diseases? And so it's really very interesting. And there's a whole lot that's being done to look at these, as they called, unexpected heroes, those who are living for really long periods of time. Now--

[00:10:03.39] AUDIENCE: What did they die of?

[00:10:07.85] DEBORAH ROACH: Honestly, I don't know. But I have had friends of mine who are in this field. And they get so frustrated when the doctor then signs what did they die of? Old age. And-- yeah, yeah. But that-- I don't know. I don't know if there are any physicians in the room, are there? Yes--

[00:10:29.69] AUDIENCE: I'm a retired pediatrician.

[00:10:31.03] [INTERPOSING VOICES]

[00:10:33.23] --be helpful.

[00:10:34.82] DEBORAH ROACH: OK. So you won't be able to speak to that. But it is a good question. And I don't remember with respect to Madame Calment and Mr. Kimura. But--

[00:10:47.39] AUDIENCE: Maybe there was no autopsy done, right?

[00:10:49.53] DEBORAH ROACH: Right. That's true, too. That's true, too. It's a good question. So what I wanted to do was I wanted to take you-- actually remind you of one of the things that actually the paper that you read all raised. And that was this idea that, in fact, we have increased lifespan over time in a very dramatic way. And this is, this is actually life expectancy. Life expectancy is basically the average lifespan of a group of individuals who are born in a particular year.

[00:11:32.37] And so what I'd like you to see here is that, in fact, life expectancy was, from the 1700s, until to the mid-1900s, was pretty flat. It was about 30, 35 years. And then we've had these dramatic increases in life expectancy. And such takes us to the point, as mentioned in your reading, that we have Hong Kong and Japan who have a life expectancy now of 85 years, OK? So that's the average lifespan.

[00:12:12.79] So there are many more people who are going to be living to really late ages, given this change. It's been a dramatic change. In fact, the change was-- this was a very linear change here. In other words, every 10 years, there was an increase in life expectancy about 2 and 1/2 years, so really, really fast. Any suggestions about what was going on here?

[00:12:39.66] AUDIENCE: Penicillin, maybe?

[00:12:40.86] DEBORAH ROACH: Yeah. Clearly, a lot of antibiotics and all sorts of things, yes, that would have impacted mortality rates.

[00:12:54.90] AUDIENCE: Vaccines.

[00:12:55.81] DEBORAH ROACH: Vaccines, yes. And, so clearly, a lot of health advances, but a lot of social advances as well. Hygiene, you think from the-- going from the mid-1900s until now, things like hygiene, just basic socioeconomic levels, increasing food and lifestyle. And so--

[00:13:21.24] AUDIENCE: And infant mortality--

[00:13:22.08] [INTERPOSING VOICES]

[00:13:23.96] AUDIENCE: Those figures are funny because they-- again, somebody, everybody.

[00:13:30.04] DEBORAH ROACH: That's right. That's right. Infant mortality is the biggest point in the lifespan that has changed with respect to mortality rates during this period of time. But there is also all age mortality has actually improved as well, even for the elderly. But infant mortality is one of the key factors which has led to this. And there's a lot of discussion in the literature about whether or not we're reaching a limit, and things are going to start to slow down or not. But it is resulting in an extremely extended lifespan.

[00:14:08.32] Now what I want to do is also mention that environment is something that's very important. And one way we can see how the environment is important is to look at the US. And so this is life expectancy by state. And I always find it fascinating that, in fact, there is such a range here. So the best performing countries primarily out in the West have a life expectancy within the state between 78 and 80 years old. And those are the worst performing. It's almost 10 years less than that. It's 71 to 75 years. And that's this purple color here. And--

[00:15:01.47] AUDIENCE: Let's go somewhere else.

[00:15:02.79] DEBORAH ROACH: Pardon me.

[00:15:03.30] AUDIENCE: Let's go somewhere else.

[00:15:04.59] DEBORAH ROACH: Yeah, that's right. That's right. Yeah. That's right. Even in Virginia, we're not doing as well as we might-- as we might like to. But yes--

[00:15:13.50] AUDIENCE: So it doesn't take ethnicity into consideration, I suppose. The West coast is your Asian population.

[00:15:22.10] DEBORAH ROACH: Well, I think that you're raising a really good point. And that is that there's a lot of heterogeneity in the US. And so in fact, that's why the US is not one of the best performers. The US is ranked like 47th in terms of life expectancy compared to other countries. And a lot of that is due to the heterogeneity with respect to ethnicity, with respect to socioeconomic situations, and things like that are really--

[00:15:52.48] AUDIENCE: --comparing states, migration patterns, where people want to live-- half the state of Washington--

[00:15:59.00] DEBORAH ROACH: Yeah.

[00:15:59.82] AUDIENCE: Yeah. I mean--

[00:16:00.82] DEBORAH ROACH: That's absolutely right. And in fact, there are also differences among states. And I'd love to superimpose another map to show these differences in terms of issues with respect to socioeconomic levels, but also things like addiction, and things like that. As we know, we've heard about the opioid crisis. And we know that it's been isolated in certain parts more than others. And that has an impact.

[00:16:35.91] AUDIENCE: I think that Florida surprises me. I would have thought that would have been--

[00:16:39.58] DEBORAH ROACH: Yes, yes.

[00:16:40.68] AUDIENCE: --top of it. But I guess all those old people are dying.

[00:16:43.84] [LAUGHTER]

[00:16:46.32] DEBORAH ROACH: Thank you. That, they do OK. So what's the take-home message here? The take-home message is that when we think about lifespan, really, there are-- let me go back a second, and to say that when we think about lifespan, one of the things that's very important is environment. A lot of the things that we've been talking about are environmental impacts on lifespan.

[00:17:16.89] And so when we think about also this expanding life expectancy, and so forth, what we also want to recognize is that as we increase lifespan, there's this area of healthspan. We, sort of, mentioned that a little bit earlier. And this is an idea that you're fairly healthy for some part of that lifespan. But then there is this phase of the lifespan where you are suffering from age-related diseases.

[00:17:53.32] And so when we start thinking about aging and understanding aging, we want to-- ideally, most of us don't really want to keep pushing out lifespan so much, especially if it means pushing out this period of age-related diseases. Really, what we'd like to do is to maximize this period of healthspan, and then have a very small period of age-related diseases.

[00:18:27.67] And to go back to what we've been talking about with respect to lifespan across the US, and historically, we have to recognize that both the environment and aging are determining lifespan. And the goal of most aging research these days is not so much to increase lifespan as we historically have been, but really to try to figure out how we can tackle this piece. And so we'll be talking about that in multiple different ways.

[00:19:06.84] And there is some good news, though. And that is that, in fact-- When we think about lifespan, there is a very large-- as we've been talking about, there is a large environmental piece. And so that means that, in fact, we can do something. It may not be as complicated as we may have thought.

[00:19:37.06] So what I'd like to do is to say, OK, so what is aging? Now OK-- now your reading for the session today talked about how much historical interest there has been in finding the fountain of youth. It's this idea that we're going to find this restorative spring. We're going to all jump into it. And then we're going to come out the other end. And we're all going to be young again.

[00:20:17.17] I like this painting from the 1500s, where, in fact, they're bringing in old ladies on carts and on stretchers. And they get into these restorative waters. And then they come out as young males on the other side. And it all suggests that, in fact, there is something special going on. But in fact-- and that we just have to find the right answers. And we'll be able to solve all this problems. In fact, you know the stories about Ponce de Leon, who went out to look for the fountain of youth. And what did he find? He found Florida.

[00:20:57.42] [LAUGHTER]

[00:21:03.29] AUDIENCE: And they're all white there. They're all white. That's, you know, an interpretation. But there were Black people.

[00:21:09.09] AUDIENCE: Really?

[00:21:09.74] AUDIENCE: I know these ones.

[00:21:11.96] DEBORAH ROACH: So--

[00:21:13.67] AUDIENCE: I've never been to, is it called Albemarle dermatology. But is that what it looks like?

[00:21:20.87] DEBORAH ROACH: You're right.

[00:21:21.74] AUDIENCE: They seem advertised--

[00:21:22.59] DEBORAH ROACH: --restorative, yes.

[00:21:23.41] [INTERPOSING VOICES]

[00:21:25.28] AUDIENCE: --facials and restorative this and

[00:21:27.29] [INTERPOSING VOICES]

[00:21:28.19] DEBORAH ROACH: Well, this is a big business, with advertising yourself is doing some anti-aging type of restoration. Yeah, it's a big business. So there is some good news when we look in the natural world. And that is that there are some species that can escape. And I'm going to tell you about one of them. And that's the lobster. And you'll never look at lobster again the same way.

[00:22:00.86] So negligible senescence. Senescence is-- and is what we're referring to as aging OK? And negligible senescence is that here's a species that doesn't seem to show any aging. Well, how does it do it? So what happens, a lobster continues to get bigger as it gets older. And as it gets bigger, a big lobster, it's about two feet long, can make about 100,000 eggs, huge level of food production. And as they get older, they make even more eggs.

[00:22:43.14] And so what happens, though, is that as they get bigger, they have this hard shell on the outside. And what they're going to do is they're going to shed their aging body and throw it away. So basically what happens is that this lobster will then-- the skin cells under the shell start to get enlarged.

[00:23:10.69] And then basically, they drain the calcium out of the shell, because they're going to need that calcium later on. And then they're going to basically pump seawater in and throw off their body. And just before this, what they've been doing is making the foundation for their new shell. But with-- this would be like throwing away all our skeletal-- all--

[00:23:41.89] AUDIENCE: Does that happen all at once?

[00:23:43.69] DEBORAH ROACH: No. In fact, when they're young, it does it about-- they do it about five or six times a year. And when they're older, they do it about once a year. And so-- yeah, come on in. So the idea is so in fact, they don't age.

[00:24:07.33] AUDIENCE: But we get rid of ourselves every seven years, don't we? We replace them, more or less, all of them.

[00:24:12.25] DEBORAH ROACH: Not all of them. And the trouble is that we're accumulating other damage. And so--

[00:24:18.55] AUDIENCE: Not fast enough.

[00:24:19.87] DEBORAH ROACH: No, that's not enough just to get rid of ourselves, because we've got a whole lot of other things that are getting damaged. But this is one way to, in fact, to have no aging. But I want to ask you a question. So do you think that to say that the lobster doesn't age, do you think it lives forever? Is it immortal?

[00:24:41.80] AUDIENCE: It's a different lobster.

[00:24:43.49] DEBORAH ROACH: No, no.

[00:24:44.50] [INTERPOSING VOICES]

[00:24:47.38] No, let's just say this one individual, OK?

[00:24:50.92] AUDIENCE: Well, it's changed everything.

[00:24:53.59] DEBORAH ROACH: It has changed, yeah.

[00:24:55.09] AUDIENCE: Doesn't a lobster have organs?

[00:24:57.28] DEBORAH ROACH: It does. It does. It does. And in fact, they have-- their organs actually have cells that have the ability to constantly continue to repair, and so forth. And so they've got other mechanisms as well. But the throwing away of the body, except for those internal organs, is something that's the most--

[00:25:23.56] AUDIENCE: Is a 15-year-old lobster as tender as a-- yeah. Really, I mean, so you got this 27 pounds lobster, we would enjoy the meat.

[00:25:35.65] DEBORAH ROACH: Yes, Yes. Yes, exactly. But you know what's interesting? And this-- just mentioned this. There's this wonderful book by Trevor Carson on The Secret Life of Lobsters. And it's really about conservation of fishing with the fishermen, and then all of the biologists who want to be sure that you've got the idea that you're preserving the oldest individuals to keep the populations going.

[00:26:08.70] And so in fact, there's a very narrow window that you're allowed to keep the lobsters, because these big mamas, if you will, are very critical to keep the population going. But an individual lobster, if it can continue to get bigger and so forth, over time, it's not going to live forever, OK? It's just not going to age. It's not going to get any older.

[00:26:39.86] But there are other things that go on. There are other-- mortality of a lobster is also dependent on the environment. Every organism encounters some level of environmental mortality. It may be constant, but it happens. And so even by accidents or whatever random chance alone, age independent mortality is happening.

[00:27:04.69] AUDIENCE: Are they easier prey for other animals--

[00:27:08.41] DEBORAH ROACH: No.

[00:27:08.83] AUDIENCE: --when they get older?

[00:27:09.85] DEBORAH ROACH: No, don't think so. I don't think there's any evidence that that's the case. So, in fact, the general thought is that there's sort of a constant probability of dying with age, but that that's fairly constant with age. And that's actually how you would define not aging.

[00:27:29.48] AUDIENCE: They get diseases, or--

[00:27:33.38] DEBORAH ROACH: Not that I-- honestly I don't know.

[00:27:36.35] AUDIENCE: OK. How do they die? I can hardly wait to hear--

[00:27:40.40] DEBORAH ROACH: Well, there are situations with predators that come along. And actually, one of the things, one of the most vulnerable stage in a lobster, then we're going to have to go on, the most vulnerable stage in the lobsters, when they throw off their skin, they throw off this body. And in fact, they haven't actually solidified this hard outside shell. That hard outside shell prevents a lot of predation. But before in between times, when they don't have that shell, they're actually very vulnerable.

[00:28:14.53] AUDIENCE: Certainly. All right.

[00:28:15.90] DEBORAH ROACH: Yeah, yeah. Yeah. So I've mentioned that, in fact, that no aging means that, in fact, there's this constant chance of dying just due to predators and other environmental factors. And in fact, aging is then this idea that, in fact, your chance of dying is actually going to be increasing over time.

[00:28:43.61] Now, I want to show you this as we transition here to say, what is aging. And I want to show you this with respect to a beautiful. picture here, painting, actually, that represents the bridge of life. But it actually was a very specific painting. And this painting was put together in response to the Benjamin Gompertz, who, in 1825, put together the mathematical, a good mathematical understanding of how death rates change with age. They increase in a linear fashion. And they keep increasing as you get older. And that's depressing. But anyway, we'll get back to that.

[00:29:39.85] And this picture actually shows this very nicely. And that is that as an infant, some individuals may be carrying genetic diseases, and so forth. And so this skeleton here with the skull on the top is representing ancestral diseases that some infants may die of very early on in life. But then this child and young man have very few things except random chance sorts of things that are impacting their death rates.

[00:30:14.76] And the way that's represented here, this is very violent. The way this represented is that as we go through ages of life, these weapons that are used to cause mortality, if you will, become more and more accurate. OK. So here a bow and arrow here, and some sort of a musket here.

[00:30:38.73] And then here, just remember, this is from the 1800s, this was the ultimate weapon, which was very accurate, the Winchester rifle. And so over time, these causes of mortality become more and more accurate, and more and more precise until life ends, and some limit is reached. And so this was basically to depict this idea that, in fact, the older you get, the higher the chance you have of dying. And that's one of the fundamental features of aging.

[00:31:19.50] But I want you to-- I really want to translate that into something that makes sense. And I'd like to think about it as a balance between damage and repair. So when we're young, then we have-- there are a number of things that can cause damage. And we'll talk about those in a second here. But when we're young, there's a very nice balance between damage and repair. And most there's-- what little damage that occurs with respect to environmental factors, for example, the repair systems were working too. And everything's in very good shape. And in fact mortality is very low.

[00:32:12.74] Then as we get older, damage levels increase. And so-- wait a second here. The repair processes may also increase to a certain extent. But then the repair processes themselves may start to decline. And so we get this imbalance between damage and repair. Now, from a-- yeah, let me just leave that there like that, because what I want to do is I want to take you to the next slide here.

[00:32:46.49] And this is what I've been talking about. And this is this balance between damage and repair. And what's determining that? Some of it is our genetics. But a lot of it is environmental factors. Environmental factors are increasing the levels of damage. And when there's a lot of damage, there's repair. But there's a lot of unrepaired damage that starts to accumulate with age. And the higher the levels of damage accumulation then lead to aging, lead to this functional decline, and lead to the susceptibility to age-associated diseases and cancers.

[00:33:39.28] Before I go on, does that make sense at this point? OK. And I want to use one example just to let you know-- give you an example of this in a little more concretely. I want to talk about the accumulation of DNA damage in the body. And when I talk about the environment, I'm talking about things like radiation, chemicals, toxins, that sort of thing, which can damage the DNA. And I'm also talking about metabolic processes that are occurring. And we'll talk more about that in the next session that we'll have.

[00:34:20.00] But in fact, even metabolism creates damaging materials that can then have an impact on the amount of DNA damage. And then what happens is that with this accumulation of DNA damage, we actually have a decline in cellular functions. We have cell death. We have aging of the body. And also, as it turns out, we have a decline in DNA repair mechanisms. And then we have this, again, accumulation of damage, which is then contributing to aging.

[00:35:04.89] Now in your reading, the reading talked about the hallmarks of aging. And I don't want to spend a lot of time on this. But I did feel that given that it was in the reading, I wanted to mention what they were talking about. And so here, we have things like genomic instability that's associated with cancers, and that sort of thing. And all of these are processes that are fundamental to the biology of aging.

[00:35:44.37] And generally speaking, there are, depending on who you read, they're either 9 or 12 fundamental processes that are getting damaged, increasing the levels of decline in function. And these are then genomic instability, epigenetic alterations. So what that means is that our DNA is actually getting these caps on them. And we're going to talk about this in a few minutes a little more. But our DNA is getting modified with these chemical markers, which then end up turning the genes off. It's not changing the structure of the DNA. But it's actually turning genes off. And well, let me hold back and talk about that a little more later.

[00:36:41.93] And I'll just tell you about a few more of these things. But our chromosomes actually have these little caps on them. And over time, those caps get smaller and smaller and eventually reach a limit. And so we can't go through the cell cycle. And what we do, what we end up with is we end up with a lot of dead cells in our body. We have this accumulation of dead cells in our body. And so one of the pathways that we need to then try to sort out is how can we get rid of that? But this declines in telomere function can lead to immune system problems, and all sorts of things.

[00:37:28.38] And let me just talk a little bit more about one of these, and then we'll move on. This idea of proteostasis, and this idea that there's this accumulation of proteins in the body, which are no longer folding correctly. And there are all these errors that start to accumulate. Well, those are the types of errors that are associated with Alzheimer's, with Parkinson's, and with cataracts.

[00:37:58.51] And so all of these changes that are occurring at the cell level in the body are not only themselves creating functional problems for us, but they're also interacting with each other as well. And so there's a lot of cross-talk here between all of these different changes that are occurring. And the take-home message is aging is really complex. And again, there's no one answer that we're going to come up with that's going to be able to sort all this out.

[00:38:40.74] And the idea is that we have this accumulation of damage, which then results in these functional declines. But it's only really if we understand this biology piece of it, which we're only just beginning to understand. Are we really going to understand how we may be able to ameliorate some of these conditions?

[00:39:06.18] So I don't usually use bullet points in my slides. But I am here because I want to be sure that we get all of the different pieces, if you will, of what aging really is. So aging is time independent. Some of us are aging fast. And some of us are aging slowly, even if we're the same age. It's progressive, cumulative, increases in damage. And that's-- we can't-- everybody is experiencing that. That's a universal feature.

[00:39:47.92] And it's caused by both extrinsic and intrinsic factors. As I said before, some of it is-- a lot of it is the environment, toxins, and so forth. But it's also intrinsic. There are metabolic processes that are creating these wastes that are causing the damage. It results in the deleterious loss of physiological, structural, and cognitive function. We all know that. And eventually ends in death.

[00:40:17.90] Now. It's unpredictable. And I think that one of the other things that needs to be understood is that it's universal. If we look across all of the different species that show aging, every individual on that. species, whether it be humans or horses, they all age. And it's something that's shared among them. So what I want to do is to shift a little bit and ask and say, take you back to the reading and say, is aging a disease? I'd like to ask that question.

[00:41:08.28] AUDIENCE: No, good point.

[00:41:09.47] AUDIENCE: No, don't think so. I think it's just lifespan determined. Because if we-- like a butterfly has a lifespan. All Different organisms have lifespans. And we have one of them. And when I just see it all around, it's sort of like people get to be 80. It's like there's something that happens that's qualitatively different. And then--

[00:41:36.26] AUDIENCE: Yeah. Yeah. Yeah.

[00:41:38.73] DEBORAH ROACH: And how is that different than other disease?

[00:41:42.12] AUDIENCE: We all have-- we all have diseases from acne. I mean, and they're age-related. I mean, I don't have acne anymore.

[00:41:49.36] [LAUGHTER]

[00:41:52.37] DEBORAH ROACH: Yeah, yeah.

[00:41:55.60] Well, yeah.

[00:41:57.00] AUDIENCE: So different things happen at different times in a human being's life that aren't-- looking for a cure of aging is just going to happen.

[00:42:07.80] DEBORAH ROACH: Yeah, that-- yeah, that's-- does anyone else want to comment?

[00:42:11.59] AUDIENCE: Well, I was so unsettled when I read that it was a disease. And that's what the article says. I thought at the end, it would say, aging is not a disease. But that's not where it ends. It's still it's that position forward. But it's hard to think of aging and disease in the same sentence. But that's what you want us to do.

[00:42:35.26] AUDIENCE: I thought just the opposite.

[00:42:36.85] DEBORAH ROACH: Yeah, so-- yeah.

[00:42:38.32] AUDIENCE: That's what I got out of it is aging is not a disease, something that happens. And as far as I can tell from what I read, the disease is something that occurs at any given moment during the aging process. But it's not the same. And we probably be happy have you explained what you really mean by that.

[00:43:06.60] DEBORAH ROACH: Well, one of the things-- I mean, I think you've both-- this is good because I can take off from this here. Because first of all, not every-- we don't all suffer from the same diseases. We all suffer from aging. But we don't all suffer from the same diseases. So that's one big difference between aging and disease. We can't cure aging. But we can hope to cure most diseases, OK? We don't talk about a cure for aging as we talk about a cure for a disease.

[00:43:48.44] AUDIENCE: How do we know we can't cure aging?

[00:43:52.80] DEBORAH ROACH: Because even-- I'm going to show you-- well, let me just flip to this for a second and show you that if we were to eliminate diseases, and particular, age-related diseases that we are vulnerable to-- if we were to eliminate heart disease and cancer, we would actually only add about seven years life expectancy. And we would be susceptible to other diseases.

[00:44:25.51] AUDIENCE: Yeah. I'm not thinking of eliminating diseases as eliminating aging. I'm thinking of it as a different process of eliminating the damage that's done somehow, damage that's done, sort of, all over our bodies.

[00:44:43.45] DEBORAH ROACH: Right. And, in fact, I think that there's a general consensus that what we want to figure out how to do is to push out the functional declines that are due to the accumulation to the latest ages. Aging biologists-- or biologists, excuse me, not aging biologists. Biologists study aging. Really, they use the expression, they want you to die with your boots on. In other words, you have-- you try to figure out how to push off the functional declines, the susceptibility to the age-related diseases to the very, very last stage, and keep that as short as possible. But we won't-- there's no expectation that we'll be able to cure all the aspects of aging.

[00:45:32.78] [INTERPOSING VOICES]

[00:45:35.68] AUDIENCE: --that you showed that arrow [INAUDIBLE].

[00:45:38.91] DEBORAH ROACH: That's right. That's right. That's right. But to get to your point, Beverley, about what the paper was saying, my understanding of what the paper was saying was that, in fact, there are differences between aging and disease. But they were suggesting, well, maybe to get bring attention to any say, drug that may be available to actually put off or to delay aging to a later age, the only way that we're going to get the FDA to notice that is to call-- is to somehow, yeah, put these two things together, because aging is such a complex thing.

[00:46:30.49] It's hard to make it sexy in terms of funding, and that sort of thing. And so I think that that's really what the point was, was we're-- how can we-- how can we get the funding that's necessary? Because, in fact aging itself, you go to the National Institute of Aging, and in fact, people are studying age-related diseases. They're not actually doing a lot with these actual processes, these hallmarks of aging decline--

[00:47:02.68] AUDIENCE: The age-related disease can be something that occurs among people of a certain age and still not be-- it's kind of a correlational relationship, and not a causational--

[00:47:16.20] [INTERPOSING VOICES]

[00:47:17.76] DEBORAH ROACH: --causation.

[00:47:18.72] AUDIENCE: --business in this paper. It's just have to look at it very carefully.

[00:47:24.48] DEBORAH ROACH: That's right. And it's that causation, it's that basic biology, which is what we need to get at.

[00:47:30.31] AUDIENCE: You can intercede and alter those processes.

[00:47:33.22] DEBORAH ROACH: Yeah, yeah.

[00:47:34.02] AUDIENCE: Otherwise-- so age-related disease, to me, is just in this-- in my group, there's more likely to be Alzheimer's. And then now that's not a good thing. So what do we do about it--

[00:47:49.78] DEBORAH ROACH: What do we do about it? That's right. That's right.

[00:47:52.29] AUDIENCE: --into that.

[00:47:52.96] DEBORAH ROACH: Yeah. Yeah, absolutely.

[00:47:55.18] AUDIENCE: OK.

[00:47:56.88] AUDIENCE: Well, age-related disease, there are clearly genetic diseases that are age-related that are not primarily environmentally determined.

[00:48:07.77] DEBORAH ROACH: Well-- but there are-- but there are environmental factors, which may mediate the seriousness of any of those age-related diseases. So I think there's a combination of both genetics and environment that are important. But yeah. Yeah, you're right. You're right.

[00:48:26.69] AUDIENCE: And one of the things that-- I'm sorry I was late. I had a trouble-- I'd never been to this place. I'd had trouble finding it.

[00:48:33.69] AUDIENCE: Many of us did.

[00:48:35.61] AUDIENCE: age-related.

[00:48:37.72] AUDIENCE: I was at NIH. And there was one researcher who was able to actually transplant young-- transplant the thalamus in rats. And you can actually see on the slides the difference between the young cells and the old cells. Now, I don't know what that would have to do with human beings, but it certainly would have to do with what you're talking about, that the young cells can recover or can repair some of that damage, and the old cells cannot. But this was in the same living organism in the brain that have some young cells and some old cells.

[00:49:18.63] DEBORAH ROACH: Wow, wow. Yeah, I don't know about that work. But it sounds fascinating. Yeah, yeah. That's neat. I don't want to run too-- I know I'm not even going to get through everything I was going to do. But let me-- let's go on here. Because what I'd like to do is I'd like to show you these two gentlemen here, OK? Now, how old do you think they are? Anyone want to take a guess?

[00:49:53.35] AUDIENCE: Well, there's a gentleman sitting right next to me. And I missed his age by about 15 years.

[00:50:03.64] [LAUGHTER]

[00:50:06.45] AUDIENCE: I'm actually 42.

[00:50:07.52] [LAUGHTER]

[00:50:16.02] AUDIENCE: Are they the same age?

[00:50:17.11] AUDIENCE: I was going to say that--

[00:50:18.16] DEBORAH ROACH: Yeah, yeah. Yeah, they are. They are. They're both-- they're both actually 72. This was part of-- one of my colleagues was working with Danish twins. And the Danish twin study is a really big study that they've been following people for a long period of time. And they asked nurses, they show them photographs and say, how old do you think this is, and this person is, and then show another picture. And how old do you think this person is?

[00:50:55.62] So the perceived age of the gentleman on the left was 80. And his brother, who was the same age, was perceived to be 73. And that's like summarized here at the bottom of the slide. Those who looked older had a higher probability of dying. And even after just, just two years. And so this is really interesting, because, as we talk about aging, and as we try to figure out how are we going to measure how fast someone is aging, we need a meter. We need some way. We need some way to be able to identify how old people are, and what their susceptibility is to dying, what their functional situation is.

[00:52:03.27] But I have to tell you that even in the lab, if you have nematode worms, and they're all genetically clones of each other, and they're in exactly the same environment, and they have different rates of aging. So there's some random chance that's going on, too. And so we don't really know how to-- the puzzle has been to figure out how are we going to measure aging and understand the damage levels that are accumulating. And yeah.

[00:52:41.81] AUDIENCE: --just having two really quick comments there. Probably, many of us have been to 50th high school and college reunions. And the perceived age of our classmates, the differences is really strange.

[00:52:53.48] AUDIENCE: Amazing, isn't it? Yeah.

[00:52:55.85] AUDIENCE: And this is another strange comment. I wondered if the older-looking brother had had a hair transplant, had had Botox, had had a different wardrobe, might he have been treated differently by his physician? Might he have-- might there have been other things that influenced the death rates?

[00:53:18.15] DEBORAH ROACH: You're right.

[00:53:19.95] AUDIENCE: Are they identical twins?

[00:53:22.38] AUDIENCE: No.

[00:53:24.66] DEBORAH ROACH: Yeah.

[00:53:26.24] [INTERPOSING VOICES]

[00:53:28.21] --they've got-- yeah. And so-- and they've got-- they're both-- they did this for both men and women.

[00:53:34.64] AUDIENCE: I guess the question would be if they were identical twins, would they look the same?

[00:53:39.98] DEBORAH ROACH: Right, right.

[00:53:40.86] AUDIENCE: Because of aging.

[00:53:41.94] DEBORAH ROACH: Right. No, the answer is no. They don't. They don't. And in fact, it's absolutely known that in fact, any way that we can measure function, and so forth. The twins actually seem to diverge the older they get in terms of their biology, in terms of their function, which is--

[00:54:06.12] AUDIENCE: Which has certain environmental factors and situational.

[00:54:09.43] DEBORAH ROACH: That's right. That's right, it does. It does. But we know from the worms, even if the environment is constant, that doesn't help.

[00:54:19.56] AUDIENCE: But before you go, that's just fascinating. So if at a certain age, what if one went into an exercise program or a training program? It seems like that should make some difference. But you're saying not necessarily?

[00:54:34.49] DEBORAH ROACH: Well, it does. And so that gets me to where I'm headed. So this idea that really what we want to do is-- these guys are the same chronological age. And so what I'm saying is that really, what we want is something that will measure biological age so that-- chronological age is how many birthday candles do you have on your cake.

[00:55:03.19] And then, on the other hand, biological age is how much damage is accumulated in your cells. And it's this-- and really, that's what we want to know. We want to be able to know who is aging at a faster rate than the next person. And the other reason it would be really nice to get these aging meters, if you will, is that-- and this takes me back to what I'd like to talk about in the bigger picture of things is, it would help us to evaluate the myths.

[00:55:41.38] It would help us to say, OK, if you take this treatment, did it actually reverse your biological age? Did it change? Did it actually make you age at a slower rate, accumulate less damage than the person who had a placebo? And that's what we want to do, is we want to be able to set this up.

[00:56:06.14] And so what I'm going to do is-- OK, I know. So the data that's being used for this is, and I'm sure many of you have probably heard about this. But there are a lot of studies going on across the world. I'm just going to talk about one of them. And that's the Baltimore Longitudinal Study. And the Baltimore Longitudinal Study has had-- it's been going on for 60 years. And it's been following people for a long time. And it's still taking in new people.

[00:56:44.92] The gentleman down here has been in the study for 51 years. And so he goes in, I believe it's every other year. And they have this whole host of physiological traits that are measured on him and all sorts of tracking that's done, both with blood samples, as well as metabolically. And they're trying to find out who are the super agers, and what sorts of markers might we be able to use to be able to develop this meter that we're going to be able to distinguish people who are the same chronological age, but different biological ages.

[00:57:34.38] So there have been a number of interesting results from this study. One of the things is something that we've already talked about here. And that is that there are more differences between people who are older than people who are younger. It's not that-- when we were younger, we used to say all old people look alike. And so they all must be. No, it's actually there are more differences. We are more different as we've gotten older.

[00:58:03.24] And really, what the whole plan is here is to try to understand what's normal aging. And the really good news, and we've sort of talked about this a little bit, is that, in fact, when we look at variation in biological age, and we look at all these people that have been coming in, repeated measures of the same individuals over time, just it's a gold mine of research and data. About 20% of the variation in performance changes over time is due to genetics, but 80% of it is lifestyle.

[00:58:46.55] Some of that's fixed. Some of that was fixed before age 30. So some of the things like education levels, early life diseases, those sorts of things, all do have an impact on this, what we're calling biological age. But they're fixed. But there are a large part, probably about 50% of that lifestyle impact on aging. It's actually also are things that we can do ourselves now.

[00:59:18.67] And that's really-- I'm going to just summarize today's talk by saying that, what we want to do is we want to measure biological age. And we know our chronological age. So there'll be those people who have a normal aging rate. But there are those who are the super agers. And in fact, as they're older, their biological age is actually much younger. And then there are, of course, those who have accelerated age, like the older-looking twin.

[01:00:03.24] And so what I'm going to do, I didn't get quite through everything I had planned to talk about today. But what I'm going to do is I'm going to take, first of all, define a nice meter for biological age that has been created. And it uses this damage accumulation on the DNA to actually measure biological age.

[01:00:33.98] And then I'm going to use that tool to then test some of our myths, some of the myths like, how does having a good supportive social structure in your life matter? Does it really matter? What about diet? What about exercise? And I want to look at those types of interventions that we hear about all the time and say, is it actually impacting biological age? Or is it just making you feel better? So that's where we're headed. And I really look forward to talking to you all. And thank you ever so much for being such an engaged group. It's been really fun.