New Developments in Aging Research

MS. DIANE REHM

11:06:53
Thanks for joining us. I'm Diane Rehm. By age 65, most people will be diagnosed with two age-related diseases. Scientists at The Mayo Clinic recently found that removing old cells in mice prevented them from developing cataracts and muscle loss. And at UCLA, researchers activated a gene in the stomach of a fruit fly that extended its life by 50 percent.

MS. DIANE REHM

11:07:34
Joining me here in the studio to talk about how new developments in aging research might apply to humans, Felipe Sierra of the National Institutes of Health. Joining us from a studio in Rochester, Minnesota, Jan van Deursen of The Mayo Clinic. This is such exciting research. I hope you'll join us with your questions, comments 800-433-8850. Send us your email to drshow@wamu.org. Join us on Facebook or Twitter. And good morning to you, Felipe Sierra.

MR. FELIPE SIERRA

11:08:28
Good morning, Diane.

REHM

11:08:29
And good morning to you, Jan van Deursen.

MR. JAN VAN DEURSEN

11:08:33
Good morning.

REHM

11:08:35
Felipe Sierra, this is not brand new research, is it?

SIERRA

11:08:44
The research that was done at The Mayo Clinic is, of course, brand new, just published, but the field of senescence has been around with us for 50 years.

REHM

11:08:54
Explain senescence.

SIERRA

11:08:57
Yes, so senescence is one of possible fates of cells when cells that normally can divide, when, for one reason or another, they cannot do so anymore. And usually this is considered -- this was described originally 50 years ago by Leonard Hayflick and it was suggested that it was related to human aging, but we have not known that as a fact until now.

SIERRA

11:09:27
Now, what has been pretty much agreed by scientific communities recently is that senescence is one of two mechanisms that we have at the cell level to fight cancer. When a cell tries to divide forever, as in a cancer, you either activate its own cell death mechanism, it gets killed or it turns into a senescent cell, which cannot divide anymore therefore it does not produce a cancer.

SIERRA

11:10:03
However, recent research has also shown that these senescent cells do not just sit there, but they secrete a lot of bad things, basically, which could or could not be one of the causes of aging and that's where we were until the recent research.

REHM

11:10:27
Now Jan van Deursen, tell us about your recent study on senescent cells in mice.

DEURSEN

11:10:37
Yes. What we did is -- so we knew about senescent cells accumulating in tissues and organs of mice and humans with age and the question we asked is, are these cells just innocent bystanders or are they actually doing bad things, such as driving the dysfunction of these tissues and organs, dysfunction that's typically associated with age-associated disorders?

DEURSEN

11:11:07
And so we designed an animal model where we could induce the killing of senescent cells, the clearance, so to speak, and what we found was that age-related diseases that were occurring in our mouse model, such as sarcopenia which is a loss of muscle mass and muscle strength which is very common in the elderly and associated with their loss of independence, the formation of eye defects such as cataracts and the loss of functional fat.

DEURSEN

11:11:49
And so what we found was that the accumulation of senescent cells in skeletal muscle, fat and in the eye actually drives the age-related pathologies and that clearing these cells is not only delaying the onset of these disorders, but can actually -- or it's not preventing those, but it's delaying the onset of these diseases.

REHM

11:12:22
Okay, so let me just recap here a little bit. What you're saying is that by virtue of the elimination of these senescent cells in mice, what you were able to do was to delay the onset of diseases in their tissues. Is that accurate?

DEURSEN

11:12:51
Yes. And I think an important finding of this study is also that we found no overt negative side effects of clearing these cells. So one big question is always in this type of research, you know, these cells accumulate for a reason. Is that reason -- is there a benefit to their accumulation? And as far as we can tell, the removal of the cells seems to be safe in our animal models, so there are no negative consequences.

DEURSEN

11:13:27
Then only positive consequences were noticed. But I would like to stress that we did not see a reversal of aging. It's not like we turned an old mouse into a young mouse.

REHM

11:13:43
So we're not talking about the fountain of youth, at least, yet. Is that correct?

DEURSEN

11:13:50
I think that's correct. Aging is a very complex process and all cells in our body essentially, over time, experience wear and tear and on top of that they experience these senescent cells that make the neighborhood in which cells live not so livable. They make it more difficult to do well so just by taking away these senescent cells, you basically improve the neighborhood in which cells live, but you're not taking away the damage that these cells have encountered...

REHM

11:14:37
I see.

DEURSEN

11:14:37
...themselves.

REHM

11:14:39
But Felipe Sierra, there's a question here. If these senescent cells are harmful, why haven't human beings evolved in a way to simply get rid of them?

SIERRA

11:14:55
Well, there are two aspects to that. One possibility, of course, is that the importance of fighting cancer for a multi-cellular organism like ourselves, the way we can grow to a size that we have and we can live for so long is precisely given by the ability of some of our cells to divide forever and that has the risk of cancer. So we evolved these mechanisms to get rid of the cancer and maybe that's a priority. Evolution cannot prevent us from developing a mechanism that keeps us healthy when we're young, even if it has a deleterious effect when we're old because evolution doesn't care about us when we're old.

REHM

11:15:41
So -- but when we are young, do these senescent cells behave differently from what happens as we age?

SIERRA

11:15:54
Not that we know. As far as we know, they behave the same, but they don't accumulate much because there's a system to get rid of them. They don't die like the other cells, the other mechanisms for fighting cancer. They do not die. However, the immune system clears them. So the senescent cells secrete several compounds that call the immune system to tell them, hey, I need to be removed.

SIERRA

11:16:25
Okay, now what happens with age is that our immune system starts failing, too, so the cells are not removed as efficiently as when we were young and that's when the problems start accumulating.

REHM

11:16:38
So from these kinds of experiments with mice, can we extrapolate and begin to think that the same process could be at work in human beings?

SIERRA

11:17:00
Well, the mechanism, as Jan probably could -- might be able to explain, because it's quite fancy genetics that they did, to be able to do this in mice so a similar way in humans will not be possible. However, the finding that the cells in these have the effects that they have makes us think that it's something that we should focus on. We should try to get rid of the cells. Before these results, we weren't sure that the senescent cells were indeed bad, now we know that they are bad and therefore there's a reason to focus either on eliminating the cells, at least eliminating their secretions, or at least neutralizing them one way or another.

SIERRA

11:17:49
It's worth doing now and I think that's where their research will go in the near future.

REHM

11:17:56
And I would certainly think, Jan van Deursen, that drug companies would be awfully interested in your work?

DEURSEN

11:18:09
Yeah, that's the case and so we have received interest from several companies. And I'm actually quite optimistic that -- we used a genetic trick to kill cells and now the next step is to find a way to clear them in humans or in mice.

REHM

11:18:32
All right, and we're going to take a short break here. You're listening to Jan van Deursen at The Mayo Clinic and Felipe Sierra at NIH.

REHM

11:20:04
And we're talking about some very exciting new research going on currently in mice and elsewhere. With me here in the studio is Felipe Sierra. He's director of the Division of Aging Biology at the National Institute on Aging at NIH. Joining us from a studio at the Mayo Clinic in Rochester, Minn. is Jan Van Deursen. He's professor of molecular biology and biochemistry at the Mayo Clinic. They are both extremely excited about their work. Now joining us from a studio at UCLA is David Walker. He's assistant professor of integrative biology and physiology at the University of California Los Angeles. Good morning, Dr. Walker. Thanks for joining us.

MR. DAVID WALKER

11:21:13
Good morning. I'm very happy to be here.

REHM

11:21:14
Thank you. Tell me about your fruit fly study.

WALKER

11:21:20
So we're interested in some of the same basic questions. We're very interested to try and understand the basic biology of aging. And in this recent study what we did was we identified a gene. The gene's called PGC1. And we made a discovery which is that if we up regulate, if we boost the activity of that gene in the intestine of the fly that's able to make the whole animal live significantly longer, as much as 50 percent in certain cases.

WALKER

11:21:53
And really at the same time we see that this, as well as extending the lifespan of the animal, we actually slow many of the hallmarks of aging within the fly intestines. So we're really...

REHM

11:22:06
How long does the normal fruit fly live?

WALKER

11:22:12
Normal healthy flies live between six and eight weeks or, you know, just under two months.

REHM

11:22:19
So I gather that would make them a good subject for your study.

WALKER

11:22:25
Exactly, exactly.

REHM

11:22:27
And when do they begin showing signs of aging?

WALKER

11:22:33
Well, just like people, the major features of aging are recapitulated in the fly when they reach around middle age. So after about four weeks or a month the flies begin to -- their reproductive capacity declines. They become much less active. They lose the ability to fly and climb. And they even lose cognitive abilities. They don't remember quite so well as when they're young.

REHM

11:22:57
So it sounds as though you're saying that there's something very, very important about the digestive tract as it relates to aging. Do you believe that that also applies to human beings?

WALKER

11:23:18
Well, that's one of the major findings of our study with respect to the fly. But yes, that we find that we can slow aging at the organismal level by slowing aging of the intestine. And the study was, you know, exclusively done in the fly. But it does raise questions about intestinal aging in other species, mammals, including people, of course.

WALKER

11:23:44
The intestine is, you know, a vital organ of course for nutrient uptake for, you know, getting energy from food. But it's also a very important barrier that protects us from pathogens and toxins in the environment. So, you know, we can -- in some ways it makes a lot of sense that maintaining healthy intestinal function as we age is very important for our health.

REHM

11:24:11
Dr. Sierra.

SIERRA

11:24:13
Yeah, I would like to add that the intestine in the fly has one particular characteristic that is unique in the fly but it's not unique in us. The intestine is the only organ in the fly that has stem cells that can actually proliferate. So maybe in us -- and I don't disagree with David on the importance of the intestine in terms of absorption and being a barrier to chemicals -- but in humans we have other tissues that share this thing with the intestine of the fly, which is we have stem cells. We have a regenerate capacity. And maybe what he's observing in the intestine being unique to him testing, in mammals it could be unique to all regenerative tissues including those that eventually could show cell senescence and things like that.

REHM

11:25:11
Interesting. And Jan Van Deursen, what's your reaction to the fruit fly study by Professor Walker? Could it be tried with mice?

DEURSEN

11:25:24
Actually it has been done in mice. There's a study by the -- where one researcher I know involved named Bruce Spiegelman (sp?) where they over expressed this gene, the PGC1 alpha in skeletal muscle. And that study shows that the mice lived longer as well. So I think that this concern that there might be some specific thing about flies that would make this gene work with regard to longevity I think has already been kind of shown in mice that it works even when expressed in a different tissue. And, Dr. Walker, correct me if I'm wrong on this mouse study.

WALKER

11:26:19
Yeah, we're -- I'm aware of that study from Dr. Spiegelman's lab, yeah. They also showed, I believe, that it delayed the onset of sarcopenia in those animals. And the same gene has (unintelligible) ...

REHM

11:26:33
What is sarcopenia?

WALKER

11:26:35
Sarcopenia is the loss of muscle tissue as a function of age. So this gene has also been implicated in a number of other age related neurodegenerative diseases such as Parkinson's disease and even Huntington's disease. So it does seem to be, you know, a potential target to intervene in aging.

REHM

11:26:58
Dr. Sierra, I've read that you refer to this study of cell senescence as the holy grail of the aging field.

SIERRA

11:27:12
No.

REHM

11:27:14
No?

SIERRA

11:27:14
Not the holy grail of the aging field. The holy grail of the senescence cell field.

REHM

11:27:21
All right. I'll take that.

SIERRA

11:27:22
Basically there are several lines of research, as Dr. Van Deursen said. Removing the senescence cells did not abolish aging. We're not going to become immortal.

REHM

11:27:33
Right.

SIERRA

11:27:34
There are many aspects to aging and cell senescence is one of them. Now when I talk about the holy grail in that sense, it's because the cells have been known for 50 years. And what has been at the center of everybody's attention is, are they really important. There's not many of them. They don't accumulate to large numbers. So the question of whether they have a physiological role in the decay of tissue function has always been in the back of people's mind. Yes, they are there. Okay, fine. Are they bad? Or maybe they are good. We don't know.

SIERRA

11:28:14
As you asked me earlier, why do we still have them? Maybe they're good. And that question actually has not been answered and will not be answered for a while. Maybe there are some circumstances that we have not tested yet in which the senescence cells will be important. For example, because they secrete these things that call the immune system into action, maybe that's -- they play a role in those circumstances. We just don't know.

SIERRA

11:28:43
But the holy grail comment was because it was so important to determine what happens if we get rid of them or if we increase them. And that's what has been done with this study.

REHM

11:28:55
We have a question from Elizabeth in Boston. "To what extent is research on mitochondrial mechanisms related to this research?" She says, "I have two sons with mitochondrial disease."

SIERRA

11:29:19
Okay. Mitochondrion has been one of the other big fields that we have been studying in aging. The free radical hypothesis which is the one that everybody says free radicals are bad for you, okay. Well, it's -- there's a lot of questions there, but the research of mitochondria has been very, very important. And things like PGC1F, for example, has been shown to be activated by resveratrol, which is another compound that people know about that helps with aging physiology.

SIERRA

11:29:57
So there's a lot to be said about how important mitochondria are. After all, they are the ones that produce all the energy that we use or most of the energy that we use. So defects in mitochondria can have very severe consequences, as unfortunately happens in these mitochondrial diseases. With aging, the effects are not as dramatic, but nevertheless there's a decay in their functioning and that plays a role.

REHM

11:30:24
Dr. Walker, what about calorie restriction? How do you think it plays a role in the aging process?

WALKER

11:30:35
Well, that's a very interesting question, very appropriate to our study. So both the role of mitochondria and also dietary or caloric restriction were one -- were an inspiration behind our study. So as Felipe mentioned, it's known that mitochondria decay is a function of age. And it's also been known for a long time that dietary restriction can extend lifespan. We don't really know the mechanism, but one of the physiological (sounds like) carlets of dietary restriction is actually boosting mitochondrial activity. And that's exactly the same physiological function that PGC1 exerts.

WALKER

11:31:10
So we -- one of the things we were interested to do was to see what if we boost mitochondrial activity via PGC1 without changing the diet of the flies. Would that have the same life extending effect as diet restriction? And as we published it does indeed when we target PGC1 to the digestive tract of the fly. So these things are -- mitochondria and diet restriction, they're all related.

REHM

11:31:36
And to you, Jan Van Deursen, are senescence cells related to the causes of Alzheimer's Disease?

DEURSEN

11:31:50
It isn't clear right now. Our model that we used -- our mouse model that we used did not have Alzheimer-like defects. One of the studies that is currently ongoing in the lab performed by Dr. Dan Baker is to specifically look at the effect of senescence all clearance on Alzheimer's disease. There is a mouse model for Alzheimer's disease and we are setting up the clearance of senescence cells. It's known that there is an inflammatory component to Alzheimer's disease which might be caused by -- or influenced by senescence cells.

DEURSEN

11:32:33
So that's a very good question. Can the clearance of senescence cells also improve the function of the brain and the central nervous system? And unfortunately our model did not -- we were unable to draw any conclusions on the existing model. But that's currently ongoing.

REHM

11:32:58
And you're listening to "The Diane Rehm Show." We have a great many callers. I do want to open the phones. First let's go to Phoenix, Ariz. and Phyllis. Good morning, you're on the air.

PHYLLIS

11:33:15
Good morning.

REHM

11:33:16
Morning.

PHYLLIS

11:33:17
This is a fascinating program for me because I am extremely elderly and a stroke survivor. And I'm wondering if they are doing any research into the brain cell that has been killed by strokes. If there is any hope for regenerating brain cells.

REHM

11:33:38
Dr. Sierra.

SIERRA

11:33:40
Well, once a neuron is killed, unfortunately there is no way of regenerating that neuron that we know of. Maybe in the future we will find, but right now, no. There is a lot of research on stroke. There's an institute in INDS which funds most of the research on stroke. But like all these age related diseases, we feel that there is a commonality to all of them that the aging processes are what's behind all of this. So in terms of treatments or cures, we don't have much in hand now. And to tell you the truth, I'm not that familiar with what the INDS funds. So I don't know if anything is on the way for that.

REHM

11:34:30
But let me ask David Walker. This notion of growing older but growing older in a healthier way is really what all this research is about. Am I correct there?

WALKER

11:34:49
Yeah, that's correct. I guess the approach is instead of targeting the individual diseases of old age one by one, what we try and do is focus on the underlying aging process itself, because as we're all saying that's the number one risk factor for all these disorders. And if we could find a way to slow that underlying aging process then we would improve the overall health of the aging population, rather than target the individual diseases. And I think that would have a huge impact on stroke, but also on Alzheimer's disease, cancers, cardiovascular diseases, all these diseases.

REHM

11:35:30
And what about other countries? Are they doing similar research? Are they ahead of us? What about that, Dr. Sierra?

SIERRA

11:35:42
Other countries are doing similar research. I was recently at the meeting in the Netherlands. Actually Dr. Van Deursen was there too. They are doing very similar type of research. Different countries of course have different capability in terms of money. Some countries are going up, some are going down in terms of their funding for research in general. So the United States of course has been a workforce in research for many, many years and we continue to be.

REHM

11:36:17
Do you think given the importance of what we're seeing both here in the digestive tract with fruit flies and senescence cells that perhaps we're focusing too much on the heart and the brain in the research that is being done here in this country, Sr. Sierra?

SIERRA

11:36:43
Well, I agree with what was said that aging is the major risk factor for all of (word?) . And I think funding for that is a priority. But I'm not going to comment on how funding is distributed.

REHM

11:36:59
I understand that. I'm just wondering about people's focus, though, and whether you'll see in the coming months and years greater focus in this direction?

SIERRA

11:37:15
Yes. We are seeing a greater focus on aging in general. However, researchers, being what they are, they tend to go wherever they think it's most interesting. And many of them have reason to go to cardiovascular and to Alzheimer's or whatever.

REHM

11:37:32
Felipe Sierra of the National Institute on Aging at NIH. Short break and more of your calls when we come back.

REHM

11:40:05
Welcome back as we talk about new research that looks into preventing disease from developing as we age. Let's go right back to the phones to Deep Gap, N.C. Good morning, Lee.

LEE

11:40:27
Good morning. How are you?

REHM

11:40:28
Fine, thanks.

WALKER

11:40:30
I'm -- this is my first time. I really appreciate the opportunity and I really enjoy your show. I've listened for years.

REHM

11:40:35
I'm so glad. Thank you.

REHM

11:40:38
Anyway, my comment is that -- no, I've been aware of ways of cleaning out senescent cells, you know, from your body, you know, for many years. And I mean, you know, there have been methods, you know, for clearing the body out, you know, for thousands of years. You know, various kinds, you know, fasting, various kinds of diets. So there are many different ways of doing this already and I'm just kind of curious as to -- now, I think the genetic research is extremely interesting, but I would also be interested to see how that would work, you know, along with these other more traditional ways of clearing out the body.

REHM

11:41:25
David Walker?

WALKER

11:41:28
Well, this question may be -- Jan, could perhaps answer this better than I since it comments on his study, but yeah, the comment on the diet, yes. We've known for a long time that restricting dietary intake without malnutrition can extend our lifespan, but the mechanism underlying that we don't know. And I think that's what a lot of us in the basic biology of aging are trying to figure out.

REHM

11:41:58
Jan?

DEURSEN

11:42:01
So Felipe mentioned that one way of getting rid of senescent cells is by the immune system. So, in essence, perhaps activities that boost the immune system could help keep your senescent cell levels down. For instance, there is one interesting study that has linked the clearance of senescent cells or at least the prevention of accumulation to exercise.

REHM

11:42:36
To exercise, healthy eating, I would think probably not smoking.

DEURSEN

11:42:46
Yes. So I think we don't know -- or without having a drug that can clear these cells it seems like common sense that a healthy lifestyle will prevent the accumulation and perhaps promote the clearance of cells through natural ways. And I think the caller is absolutely right, but I don't think, apart from the study on exercise, I'm not aware of, you know, other lifestyles that -- or proof of other lifestyles that could help keep the senescent cell levels down.

REHM

11:43:26
But, Dr. Van Deursen, is that where this might be headed toward? For example, the development of some drug therapy that could rid the body of senescent cells?

DEURSEN

11:43:43
Yeah, I think that's a very promising line of research. I think that all the research that has been done on the targeted killing of cancer cells, sort of targeted therapies, find a drug that kills specifically a kind or certain types of cancer cells and leave the normal cells, the healthy cells in our body unattached. That research has been going on for several years now. And I think the clearance of senescent cell approaches can really benefit from that research.

DEURSEN

11:44:17
And I think that clearance of senescent cells might actually be a lot easier than killing cancer cells because senescent cells cannot divide. And senescent cells cannot escape the drug as easy as cancer cells do. That's the major problem with the targeted drug therapies, is that the cancer cells mutate and find a way around a drug. And I think because senescent cells don't have the ability to proliferate, I think they will be easy targets. And personally, I'm very optimistic that there will be, maybe in addition to some lifestyle changes, that there might be specific drugs being developed over recent years that can actually attack these cells.

REHM

11:45:07
Help me to understand what happens during, for example, radiation as a cancer therapy and what that does to both senescent cells and cancer cells.

DEURSEN

11:45:29
So the radiation and chemo basically introduces DNA and protein damage. And cancer cells are somewhat more sensitive to that and die more readily after experience chemo or radiation, but normal cells also will experience damage. And normal cells, as a result of that could go into senescence. Now that we know that senescent cells do bad things, that's maybe why chemo and your radiation treatments are associated with accelerated aging. And so perhaps in the future, if you find a way to get rid of senescent cells, maybe that would also benefit people that receive cancer treatment.

REHM

11:46:23
Interesting. Dr. Walker, do you want to comment?

WALKER

11:46:26
No. I would agree with those statements and sentiments, yeah.

REHM

11:46:33
All right. And let's go to Louisville, Ky. Good morning, Annie.

ANNIE

11:46:40
Good morning. Thanks for taking my call.

REHM

11:46:42
Surely.

ANNIE

11:46:44
My question is, I've been sort of reading about the longevity diet, about calorie restriction, optimal nutrition and the whole idea is still sort of vague for me. So I don't know if you've already touched on this or not, but I'm just wondering if maybe you guys could talk about it just a little bit more. And, let's see, I had another question, what do you guys think about a vegan diet as a way to prolong life and as opposed to like eating meat or eating dairy, things like that?

REHM

11:47:13
Well, you understand these are not dieticians, but Dr. Sierra, you might want to comment.

SIERRA

11:47:23
Yeah, so there so was this thing about dietary restriction, it increases lifespan and increases…

REHM

11:47:30
Right.

SIERRA

11:47:30
…health. Those are studies, for the most part, done in animals. We don't know whether there's other effects in humans. There are some…

REHM

11:47:41
And how severe are those dietary restrictions?

SIERRA

11:47:44
Quite. Quite. Depend on the species and different conditions. They are from weaning of a mouse, in other words, from about 21 days of age until they die, a 40 percent restriction. So that's a quite -- it's not just your regular diet. That's a very -- and yet, with no malnutrition. Now, the thing that's not that clear is that your genetic background affects how dietary restriction will work. So we don't know in humans, which have a varied genetic background, they have their genius genetic background. Some of us might be helped by dietary restriction and some of us might not.

SIERRA

11:48:27
Now, if you have a heavy BMI of 27 or 28, there's no question that diet will help you. But this extreme diet that we subject the animals to, I see them primarily as a research tool to identify the mechanisms so that, like we have been doing with other things, once you identify the mechanism the idea is to develop mimetics of the diet restriction where you don't restrict yourself, but you take something that makes the body think that you are doing that.

REHM

11:49:01
I see. I see. Jan van Deursen, I'd be interested in your work with centenarians.

DEURSEN

11:49:14
Well, we're not doing work with centenarians, but what we are learning from centenarians is that they typically have a very long health span, which is basically the period in one's time that a person is free of major chronic diseases. The health span in centenarians is very long. And one interesting goal, I think, or more recent goal is not to increase lifespan so much as health span, to improve the quality of life. We're trying to learn from centenarians why their health span is so good and try to mimic that so that ordinary folks, like my family, might be able to improve the quality of their health in later years.

DEURSEN

11:50:07
And that also has of course an important socioeconomic advantage. If you can compress the period in one's life that one is dependent on doctors, hospitals and maybe nursing homes, that would decrease the healthcare costs quite dramatically. And we all know that this is very important.

REHM

11:50:37
But is there something different that you've seen about centenarians? Do they live differently? Do they eat differently? Do they sleep differently?

DEURSEN

11:50:54
Well, this is not my area of expertise, but what we're always joking about at meetings is that these people do not particularly live healthy lifestyles. They don't necessarily watch their diet. Some of them even smoke. They -- it seems like their genetic composition is such that they're resistant to a lot of age-related disease or deterioration. And we say genetic -- I say genetic because usually siblings have also -- of these centenarians -- have a long life expectancy. So there is definitely a genetic component to all this.

REHM

11:51:41
And that brings me full circle. I mean, if Dr. Sierra, you're born with a genetic makeup, that is no matter what you do, if you drink, if you smoke, if you don't exercise, if you overeat and you're gonna live beyond 100 then how does that affect your thinking about all this research?

SIERRA

11:52:13
Well, certainly that is true. If I knew that I had the genetic…

REHM

11:52:18
Sure.

SIERRA

11:52:19
Okay. I would misbehave, however, I don't know. I don't know. So the bottom line is that these centenarians are really extreme cases. There are very few of them. So the chances that my genetic components are so that I would become a centenarian are extremely, extremely -- I have low chance.

REHM

11:52:39
Low, low.

SIERRA

11:52:41
So I'd rather take care of myself, exercise, eat good and so on because I can't count on being like these ones that have been studied. Now, one thing that I would like to add, when we talk about centenarians and Jan talked on the -- touched a little bit on the cost to society. So I recently heard -- and I have not seen the data, but I was told by somebody who works with centenarians. One thing that we do know is that most of the cost of healthcare occurs in the last five years of your life, but it takes a third of the cost when you die at 100 than it takes when you die at 80.

SIERRA

11:53:19
When you die at 80, you have a slow decay that requires a lot of health services and it's very expensive. When you die at 100, indeed your health span has been increased to a point that you don't even go to the doctor when you're 80. You start going about a year before you die. And then you die very fast. So the cost of the last five years is only a third of what would be otherwise.

REHM

11:53:44
Fascinating. And you're listening to "The Diane Rehm Show." Let's go to Salt Lake City, Utah. Good morning, Tom.

TOM

11:53:55
Hi. I have two questions. So I was wondering what the difference is between health and lifespan, but I guess that was partially answered.

REHM

11:54:09
Yeah.

TOM

11:54:10
But also what point in a human life cycle these problems seem to really develop? And I guess, you know, to be frank, like, you know, if I'm in my 20's now, you know, and what's kind of the time frame that we're looking at in terms of like an actual treatment to, you know, remove these senescent cells so that, you know, practically speaking we might be able to actually, you know, enjoy this extended health span?

REHM

11:54:47
That's an interesting question, Dr. Sierra.

SIERRA

11:54:51
Well, for one thing we cannot remove the senescent cells yet so you don't have to worry yourself about that. But in terms of when you can start a treatment to prevent aging, it's unlikely that people will -- even that the FDA will approve or that people will start a treatment when you're healthy to make you live longer if you are only 20. This becomes more relevant when you are getting old. So you start thinking about it. And it starts bothering you. And in that sense, for example, the NIA funded a study that showed that rapamycin extends the lifespan and the health span, as far as we can tell.

REHM

11:55:37
Rapamycin.

SIERRA

11:55:38
Rapamycin.

REHM

11:55:39
What is that?

SIERRA

11:55:40
It's a compound that was found in the island of Rapa Nui. And that's why it is called rapamycin. Rapa Nui is what in here is called Easter Island. Okay. So this compound has been used as an immunosuppressant for transplant patients.

REHM

11:55:58
I see.

SIERRA

11:55:58
But it acts -- the molecular way in which it works at the cell level is very well known. And studies in flies and worms had shown that modifying the activity of that pathway did lead to longer life. So it was tried in mice and it did. It made the mice live longer. Okay. Now, the interesting thing is that for several reasons the treatment of the mice started when the mice were almost two years old, which has been extrapolated -- I don't know how correct this is, but would be equivalent to a 60-year-old person.

SIERRA

11:56:39
Then we're talking about something that as a 60-year-old you start thinking about what I'm gonna do when I get old.

REHM

11:56:46
Felipe Sierra, he's at the National Institute on Aging, Jan van Deursen, professor of molecular biology and biochemistry at The Mayo Clinic and David Walker, he's assistant professor of integrative biology and physiology at the University of California, Los Angeles. Fascinating work gentleman. I will be interested as I grow older hearing all about it. Thank you all so much.

SIERRA

11:57:21
Thank you, Diane.

REHM

11:57:24
And thanks for listening all. I'm Diane Rehm.
Transcripts of WAMU programs are available for personal use. Transcripts are provided "As Is" without warranties of any kind, either express or implied. WAMU does not warrant that the transcript is error-free. For all WAMU programs, the broadcast audio should be considered the authoritative version. Transcripts are owned by WAMU 88.5 FM American University Radio and are protected by laws in both the United States and international law. You may not sell or modify transcripts or reproduce, display, distribute, or otherwise use the transcript, in whole or in part, in any way for any public or commercial purpose without the express written permission of WAMU. All requests for uses beyond personal and noncommercial use should be referred to (202) 885-1200.

Our address has changed!

The Diane Rehm Show is produced by member-supported WAMU 88.5 in Washington DC.