Why We Age

DOUG MYRLAND (Guest Host): I’m Doug Myrland, sitting in for Maureen Cavanaugh, and you're listening to These Days on KPBS. There's a well-known saying that old age is not so bad when you consider the alternative. So people who live to a ripe, old age have usually considered themselves lucky, despite what health problems they may have. There is, however, a uniquely lucky set of people who live to a great age in great health and they are now the focus of a study conducted by Scripps Genomic Medicine. It's called the "Wellderly Study," and it's being conducted here in San Diego. Earlier this year, Maureen Cavanaugh talked about the research being done on healthy old age with Dr. Eric Topol, Director of Scripps Genomic Medicine, and with Sarah Topol, a nurse and clinical trials coordinator on the "Wellderly Study," and the daughter of Dr. Eric Topol. And here's that interview.

MAUREEN CAVANAUGH (Host): Well, let me start with you if I can, Dr. Topol, and ask you what does science know now about what causes us to age?

DR. ERIC TOPOL (Director, Scripps Genomic Medicine): Well, it's a very interesting and a fascinating process, of course, that is a large part genetically determined. That is, the conditions of the Wellderly is quite a heritable condition, passing from one generation to the next, so it really sets up our study very well to be able to determine what are the genes that influence healthy aging because we know these individuals are potentially destined to have many adverse conditions like heart disease or cancer or Alzheimer's but they don't get these conditions. And so, hopefully, we're going to find out why.

CAVANAUGH: And introduce us, if you will, a little to the "Wellderly Study." How did you come up with the idea to study the genes of people who are 80 or older and in good health?

DR. TOPOL: Well, it's an interesting thing because almost all the work in genetics, in this really exciting time when we can even sequence the whole genome, has been done – focused on diseases and this is really the flip side of that, to turn our interest to what keeps people healthy because we're going to, along the way, learn a lot about diseases. So back in 2006, actually, when we started to see the avalanche of discoveries and the powerful tools, we said let's apply this in a whole different way, and that's how we came up with the idea of finding people who are very different than the norm, that is to be beyond age 80 and never having been significantly ill, no significant medications. That's highly unusual, and that's the kind of people we're looking for to find out about their underpinnings.

CAVANAUGH: And in doing this research, what specifically are you hoping to discover?

DR. TOPOL: Well, we know that there are such things as – called modifier genes that basically titrate or cancel out the risk that other disease susceptibility genes are causing. So that's what we're on the hunt for, is finding what is it about these people that keeps their adverse genes in check because if we can find that out, that's really nature's way of protecting people from getting significant illnesses during their life.

CAVANAUGH: Now you're trained as a cardiologist, Dr. Topol, and I wonder what's the connection between your work in that field and this field, studying the DNA of the Wellderly.

DR. TOPOL: Well, that's a great question, Maureen. I think what's become more of reality over time is that when we treat people with heart disease, it's typically very far into the process, you know, very late in the process, once they already have blocked up arteries or they've had a heart attack or that sort of thing. And so the ultimate prevention is understanding the root cause of health and disease. So really a number of years ago there was a shift to putting a lot more energy and effort into this preventive mode, and that's really what this whole field of genomics genetics affords us, a phenomenal opportunity to move our emphasis into prevention and start working when we know what the basis is for health at a much earlier time in life.

CAVANAUGH: And you alluded to this a little bit before but what actually – what's the criteria for being a participant in this study? You have to be over age 80.

DR. TOPOL: Right, and Sarah's been the lead person to screen these people and it's a lot of work but, you know, it's really finding the criteria of – been healthy all throughout into their ninth decade and beyond without any significant illness and on no significant medications. We have some specifics of things that we allow because if you try to get no eye drops or, you know, no things that vitamins or things for osteoporosis, certain things that is very common in elderly that we – we would rule out everyone. But we are really sampling and enrolling people who are very unique in terms of their fantastic health status.

CAVANAUGH: I'm speaking with Dr. Eric Topol, Director of Scripps Genomic Medicine. He's heading up the "Wellderly Study," which is studying the DNA of people who are – have a – in great health and are also of advanced age. And I'm just about to speak to the Clinical Trials Coordinator for the "Wellderly Study," who happens to be the daughter of Eric Topol. She's nurse Sarah Topol. And, Sarah, you actually interview the people…

SARAH TOPOL (Clinical Trials Coordinator, the "Wellderly Study"): Umm-hmm.

CAVANAUGH: …who want to become participants in the study. How did you get involved in this?

SARAH TOPOL: Well, I've always actually had a passion not only for the, I guess, geriatric patient population but also for genetics. Obviously, from early on, I've been exposed to this field through my father and the work he's done which has always been very cutting edge and keeps you on your toes, really. And being someone in healthcare, that's really what I wanted to focus on, was something that would keep me kind of on the brink of something exciting. It's, as a nurse, a very different role to be in, but it's – especially this project is thrilling, it's inspiring, and it does kind of keep me motivated and actually I love my job. I love going to work. So I'm glad to be here. The people I work with are great and we have a good team.

CAVANAUGH: So suppose someone hears about this study being conducted and says, you know, I'm feeling pretty good and goes down and wants to be a participant. What's the process?

SARAH TOPOL: Well, we do have kind of a recruitment so, you know, things like this, exposing us to the public is great. We do get callers in. They can call in to 1-800-SCRIPPS and that is how we initially get contact with these people. So they actually come to us. We don't actually cold call…

CAVANAUGH: Right.

SARAH TOPOL: …an individual. So the screening process, you know, they have to be over 80 years of age and there's very specific questions we ask about their health whether they've ever had a cancer or heart disease, if they've ever had a stroke or a mini-stroke. We go through a whole list of eligibility criteria and, further, when we determine they're eligible we either talk to them about me coming to their home to visit with them and enroll them in the study, which is a one-time appointment, or they can come in and meet with us at the hospital. Sometimes if there's a large group of people in one area, I can drive to that location and meet with the entire group. So it, you know, we try to be flexible. It's a population that you need to cater to because not everyone is driving or has certain needs. So I do whatever I can to make it easy for them.

CAVANAUGH: And is there – I guess this is a sort of a hard question but are there any traits that seem common in people who you're meeting on a regular basis, who are of advanced age, and who are very healthy.

SARAH TOPOL: Absolutely, and I mean, even my own friends ask me all the time, what is their secret? Tell me. I want to know. So I really think that as a group, and my colleagues would probably say this as well, they've met a lot of the people that I meet, they're very positive. They want to live, they want to have a good quality of life. A lot of them take to their own holistic methods. If they can find another way to treat, say, prostate enlargement, they will – they'll go do whatever they need to do to avoid prescription, to avoid going down that path because they've seen their own friends maybe deteriorate because of taking too many appointments at the doctor or – but over – overwhelmingly it's the positive attitude that I see. And they – a lot of them will say I'd like to live to a hundred and ten but only if I have all of my faculties. So I do meet people that are, for example, a hundred and five who have – everything's intact. They may have some vision problems but, you know, physically, they're able bodied and they can do everything they've done their whole lives. So it's astonishing to see that and I think it comes from them wanting to be here enjoying life. They want to see their family, they want to see their great great grandchildren. And they just – they kind of exude that to me.

CAVANAUGH: We are talking about the "Wellderly Study" that's being conducted at Scripps. I'd like to take a call from Amy in Rancho Bernardo. Hi, Amy.

AMY (Caller, Rancho Bernardo): Hi there. Although my grandmother doesn't fit into the positive kind of person category, she turns a hundred and four April 14th and she is – she always thinks she's sick but she never has had a major illness ever and, oh, and she never takes any medicines. I think she's really strict on not taking any medicines. Her father died at a hundred three so there must be some sort of longevity genes. Hopefully, I have it.

CAVANAUGH: Thank you so much, Amy. Dr. Topol, that sort of confirms what you've been finding, doesn't it?

DR. TOPOL: No, it's actually perfect. It's prototypic and that's what we're on the hunt for is to find those genes that led to that centenarian status and, hopefully, for Amy as well. But, you know, we're well on our way. We're into the sequencing mode and we've done lots of genome scanning on, you know, Sarah and her team have collected almost 600 of these individuals and sounds like Amy's mother would qualify very well.

CAVANAUGH: It does, indeed. You know, we have several clips of the interviews of the people you've been studying. The first clip we're going to play is from Dr. Forest Adams. Now, this man is 89 years old. He wants to have his stem cells harvested and frozen for scientists to study. He believes the key to his longevity and good health is in his genes and he wants to help future generations.

DR. FOREST ADAMS ("Wellderly Study" Participant): Longevity's not for sissies. So, you know, as one deteriorates, what you perceived you were when you were twenty is no longer that way. I mean, all you've got to do is look at the commercials on television, it's about women's health things and they sell – everything they're selling for the face and the skin. They're talking about twenty year olds, they're not talking about fifty year olds or seventy year old women. So that part, you don't look forward to. But on the other hand, for people who are getting things that possibly could be prevented or cured, probably in the case of stem cells could be prevented.

CAVANAUGH: Dr. Topol, can you tell us a little bit more about Dr. Forest Adams?

DR. TOPOL: Well, he's a really fine example because he has reached almost eighty – ninety and has been remarkably intact and he has a interesting view about stem cells and, you know, that's actually one of the things that we think could have a foundation for healthy aging, is that people who have a ability to make stem cells and to do their own repairs of, you know, kind of normal housekeeping whether it's in their blood vessels or other tissue in their bodies, so this is a theory that is one of the major ones that account for healthy aging.

CAVANAUGH: People who sort of repair their stem cells all their life?

DR. TOPOL: Yes, they have a good way to make them either through their bone marrow or other means and they have a high circulating level of these stem cells. And so, you know, of the various candidate genes that's certainly one of the principal pathways that we think could be important.

CAVANAUGH: My guests are Dr. Eric Topol and Sarah Topol and they are Director and Clinical Trials Coordinator, respectively, of the Scripps Genomic Medicine "Wellderly Study." They are studying people 80 years of age and older who are in good health, have no chronic diseases and they're trying to study their DNA to find out how all of us can be that way. Let me, if I may, go to the phones because we have a lot of people who would like to join this discussion. And say hello to John in San Diego. Hi, John.

JOHN (Caller, San Diego): Hi. Thanks for taking my call.

CAVANAUGH: Yes.

JOHN: I have a question. I was wondering if the study was going to include the consideration of diet and how that may impact the expression of specific disease genes.

CAVANAUGH: Thank you for that, John. Dr. Topol.

DR. TOPOL: Yes, I mean, we do get some information about diet. Of course, over the course of many decades, it's hard to track that precisely. But there isn't any question that healthy aging, this Wellderly status is influenced by lifestyle, environmental factors as well. And so it's really understanding the genetic contribution that we're after, acknowledging that there's going to be things like the diet that are also quite important.

CAVANAUGH: I – Yes, and I was about to say that we actually do have two clips that sort of contrast the idea about how diet and exercise and a healthy lifestyle might contribute to a healthy old age. First we hear from George Daenel (sp), who is 82 years old. George thinks he has good genes but he also eats very well, healthy food, he exercises vigorously including riding his bike like he's a young triathlete. He attributes much of this to his lifestyle.

GEORGE DANEL ("Wellderly Study" Participant): I got a few aches and pains in the hands particularly. A little bit of knee thing, not very much. But basically I've pretty much been the same, not quite as limber, can't get up quite as fast. I can't do a handstand anymore. You know, the things that you do when you're growing up and a kid, I couldn't swim out at the Windansea like I used to do as a high school kid anymore, I know I couldn't do that. But basically I've just pretty much been the same all the years that I've lived.

CAVANAUGH: So the participant in the study, George, eats well and exercises and he thinks that has to do with his lifestyle and his longevity. But our last clip is of 80 year old Natalie Nestat (sp), who eats whatever she wants, doesn't exercise, and smokes. She's been smoking for more than 60 years, ten or twelve cigarettes a day. She believes the secret to her long healthy life is in her genes.

NATALIE NESTAT ("Wellderly Study" Participant): I do come from peasant stock, as I told you. I mean, you know, my ancestors were not wealthy people, they lived on little plots and they worked very hard where they came from in Lithuania and it's quite possible that I've just inherited them. I cannot remember my grandparents, who both came from Lithuania, ever being ill. And they were both in their late seventies, which isn't – today, is not old but for them, that was pretty good going.

CAVANAUGH: So Dr. Topol, what are we to make of this?

DR. TOPOL: Well, you know, it's really interesting, Maureen, because if you think about the people who don't eat right and smoke, they're probably the best of all of the individuals because that's where the genetics are protecting them the – the most profoundly. So, you know, I think Sarah could tell you more but I – most of the people are more in the healthy lifestyle side who don't smoke, and actually, you know, pretty thin and take really good care of themselves. But the outliers of the outliers are the ones that – like the woman you just had talk about her experience.

CAVANAUGH: Are you surprised, Sarah, when you meet someone who really has not, you know, taken much care of their health, who happens to be quite old and really, really quite healthy?

SARAH TOPOL: Well, it is surprising because of my generation, what I grew up learning about how to protect your health. I was, you know, the anti-smoking generation and I think there is a generational difference whereas tobacco and smoking was a stress relief for the generation of 80 to 90 year olds. So at this point, it – I kind of expect that they all smoked at some point in their life but I do think it's still astonishing to see people who can tell me they smoked two and a half packs a day for fifty years and they've never had asthma or never had a pulmonary disorder and never even had pneumonia. So those are things that you expect. I mean, as a nurse, I've seen that in the hospital just typically, so they must have something that is protecting them. And also, you do get a lot of information about their family background and, like Natalie was saying, her family was hardy and they lived long and she never remembers seeing them ill where I do interview people who are the only survivor in their family and they've had rampant cancer or heart disease and heart attack that's taken all of their siblings, their parents, yet they have never, themselves, even experienced hypertension or high blood pressure. So there has to be something else contributing there. If it's protecting them from that heritable disorder or something else that they have, and that's the secret, really, that we're targeting.

CAVANAUGH: That is remarkable. Let's take another phone call. From Carolyn in San Diego, good morning, Carolyn.

CAROLYN (Caller, San Diego): Good morning. Yes, I just wanted to comment. Thanks for taking my call. I have a aunt, a uncle, and a grandmother and they're 89, 91, and 93 and the 89 and 93 year old are still driving. All three of them still living on their own. I think they would be an incredible study. They're at – We're all African American, all very independent, no medications, no heart disease, no high blood pressure, no diabetes, nothing. The only thing is the aunt, she can no longer drive because of her eyesight. But…

CAVANAUGH: Carolyn.

CAROLYN: …I'm very interested.

CAVANAUGH: Carolyn, I actually think we're going to put you on hold so we can get some more information from you about your relatives. Thank you so much for calling in. Dr. Topol, that raises the question of the diversity of this study. Are – you're trying to get in all ethnic backgrounds and – and are you at a point where you can find that there's any difference between ethnic races in longevity.

DR. TOPOL: Such an important issue. Out of the 600 individuals that have been enrolled, the vast majority are of European ancestry and we know that the genetic bases is going to differ whether it's Asian ancestry or African ancestry so it's really important that we get a large cohort of diverse ancestries and so that's a really critical path for us going forward now is that we – we've done quite well with European ancestry but we've got to – and that's what's great about San Diego because they have such a diverse population and so it's great. It sounds like there may be three individuals here that are very well qualified, which is fantastic.

CAVANAUGH: That's great. I'm speaking with Dr. Eric Topol. He's the Director of the Scripps Genomic Medicine, heading up the "Wellderly Study," and his daughter nurse Sarah Topol, Clinical Trials Coordinator of the "Wellderly Study." And, Sarah, you have had your own DNA studied.

SARAH TOPOL: Umm-hmm.

CAVANAUGH: What did it say about you?

SARAH TOPOL: Well, I actually wasn't even – A lot of people think, oh, my gosh, I cannot believe you're finding out what's going to happen to you. I wasn't nervous until the day I had to open up – it comes electronically by e-mail. It wasn't, I guess, surprising. A lot of things you see in your family end up on here but there are some moments where you think, oh, my gosh, I have a 20% chance of something like aneurysm. But it is great. I mean, I think that I'm lucky that I'm alive and young in this time where you can use these to your benefit as far as I can now look to early screening for any of the diseases or conditions that came up as a high risk for me, whereas the people I meet, they say, well, should I have this test done? And I say, well, you know, in your nineties, you've probably encountered the major health risks that you have and at this point it may just be age related. But I do think I'm very lucky to be kind of in this world as we see the changes in genomics and genetic sequencing and just be able to use that to my benefit and become a Wellderly, hopefully, someday.

CAVANAUGH: Now there's nothing, Dr. Topol, that you can see in your DNA screening now that tells you you have a wellness gene for old age or anything like that but you can see if you have risks, is that correct?

DR. TOPOL: Yeah, there's almost 30, even up to 40 conditions now where we understand the common gene variance, you know, the ones that explain the susceptibility or protection. There's one that's particularly noteworthy because it is a risk for Alzheimer's and for shortened lifespan. That's the so-called ApoE4 gene and that's one of the many important genes that we're zooming in on in the Wellderly population to see, you know, how many carry that. But for the most part, the genes for healthy aging are not known at this point. And so that's only going to come through, instead of the genome scanning like the data that Sarah just reviewed of her own, this is going to have to be all 3 billion coding letters have to be sequenced in order to find these specific healthy aging genes that aren't known yet.

CAVANAUGH: Let's take another call. Linda is calling from Poway. Hi, Linda.

LINDA (Caller, Poway): Hi.

CAVANAUGH: Hi.

LINDA: I wanted to tell you about my children's godmother who is simply amazing to me because even though she's in her late eighties and has no particular diet, attributes a lot of her health to a good family background. She does a little bit of exercise and she, herself, has told me that she feels she's deteriorated a little bit in what she can do physically, is simply beautiful. In the 25 years I have known her, she has not physically changed very much. Her eyes are sparkling, her skin is glowing, and even though when you look at her you know that she's somewhat older, she is beautiful.

CAVANAUGH: Well, thank you for that so much, Linda, for sharing that with us. And I wonder, Dr. Topol, or maybe I should ask you, Sarah, when you see the people who are candidates for this study, do they look to you the way you've had in your mind, a stereotypical person in their eighties or nineties.

SARAH TOPOL: Typically, no, not at all. Most often, they probably think I'm just flattering them with compliments but I have yet to really see somebody that looks their actual numeric age. So, typically, I go and meet these people and sometimes I'm confused if they're actually the age that they've, you know, declared.

CAVANAUGH: You have to check their ID?

SARAH TOPOL: I have, actually. There have been several individuals, and I'll never forget them, that just shocked me. And totally naturally, without any, you know, surgery, have maintained their skin and they just – they look amazing. I mean, I – you'd think they were 20, 30 years younger than they actually are.

CAVANAUGH: There is something going on here.

SARAH TOPOL: Yeah.

DR. TOPOL: No question about it.

SARAH TOPOL: People would pay a lot of money for their real secret so…

CAVANAUGH: Well, let me ask both of you, if I – perhaps starting with Sarah. Is there sort of like a physical model, a typical look to a person who is going to be very well at an old age? You know, is there a weight component to this? Or anything like that?

SARAH TOPOL: Well, we all – we always look at the body mass index, height and weight combined, and there really isn't a trend, I'd say. There are – there's definitely a trend towards a slimmer person but there's not a trend either way as far as, you know, how much overweight people generally are because not everyone is, you know, the slender, perfect physical body. But there is a trend towards shorter stature and that's both male and female. There are some outliers that are very tall. We do have – I think the tallest female is 5'10" and the tallest male is probably about 6'3". But there's generally a shorter stature which my dad could tell you is, throughout the species, very common for predicting longer life or longevity.

CAVANAUGH: Isn't that strange, Dr. Topol? Any reason for that?

DR. TOPOL: You know, it's interesting but it's never been discovered but across every species and now it appears to be in man as well, shorter stature is an advantage. So shorter dogs live longer, horses, elephants, and man so that's also not just longevity but as we're starting to uncover because this study is not just about, you know, how long you live, it's about how healthy you live during that time. And that short stature appears to be an advantage and that's going to be really interesting because there's a critical gene and a pathway with insulin that determines height, and that may tie into, you know, one of the stories here about healthy aging.

CAVANAUGH: You know, I do want to just make sure that we clarify something. Probably it'll turn out that most of us don't have this great gene.

DR. TOPOL: Well, there'll be more than one, Maureen. There'll be many.

CAVANAUGH: And I wonder if the whole idea that people who live to advanced age in your study in great health often sort of abuse the idea of what you should do and how you should exercise and eat and smoke and all of that. For the rest of us, it's really rather important, isn't it, Doctor, that we do take good care of ourselves?

DR. TOPOL: Well, that's right and it's going to take a while before we get all this stuff unlocked and, of course, many other groups are working on this as well. But I think the biggest thing is whereas in the past it was thought that being able to manipulate healthy aging was taboo, it was – you couldn't even think about it, now the science and the whole genomics is getting so advanced that it is now in the specter of possibility, and that's a big shift in thinking. If you were to say, oh, I don't have any of these genes – but once we understand the biology, it's possible that we'll have, you know, a means, whether it be pills or other mean strategies and it could even be through lifestyle and diet, to help people have a healthier aging process.

CAVANAUGH: And if we can, Doctor, let's just play around with this for a minute. How long do you see humans being able to live?

DR. TOPOL: Well, it's predicted that – it continues to go up, of course, and so life expectancy now is already in the 80+ in this country, and except for the obesity and the so-called diabesity problems related to the diabetes, it's projected that it'll continue to rise over the next 20, 30 years, well into 90 and eventually, you know – the question is, what would be the upper limit? It's projected that could be 120 but is that going to be the norm? No. And, of course, is anyone going to want to live that old if they aren't healthy and having a high quality of life? So that's really what this project is zooming in on, is not just about longevity. And so that, I think, is the critical question, is how can we extend life span with it really encompassing health span.

CAVANAUGH: And I wonder if you've toyed around with any of the social implications of your work? Suppose, indeed, you do find a sequence of genes that sort of – and you can manipulate them in a way that the diseases of aging don't crop up and people are healthier and they're living longer and longer, do you see any societal impacts to that kind of work?

DR. TOPOL: Well, yes. Because if people are living longer, that's going to extend the burden of the – a lot of our healthcare, of course, is for the aged and when the aged are reaching their end of life care that's, of course, a big part of the cost. So there isn't going to be any question that if we're successful, we create a new problem. So -- But, you know what, I think by that time, hopefully in the years ahead, we'll have other strategies that will counterbalance the potential increased cost burden of having a much larger population with healthy aging. And we've already seen, of course, and, you know, I think Sarah can attest at how productive these people are to society. I mean, the – a lot of them are still working, which is amazing.

CAVANAUGH: Yes.

DR. TOPOL: So that's another part not to discount in any way.

CAVANAUGH: And I also want to ask Sarah, in closing, do you have all the participants you need? Or would you like more people to be signed up for the study?

SARAH TOPOL: We're definitely seeking out more people and it'll continue for at least the next year. We'd like to get, at the very top, 2,000 individuals enrolled in the study and we have about 600 currently. And it's been – it's a hard process to recruit these individuals because obviously they're not coming into the hospital. They're steering clear of doctors as much as they can. So we do a lot of community work. We have a great program where we can get some exposure. Because this is a topical area, people want to learn about the future of where this is headed in our department. But it is, it's tricky. A lot of recruitment is through the individuals who participated. George, for example, who you heard earlier in the clip, he's been phenomenal at approaching people at his gym. He has a lot of friends who are active, and just amazing individuals who then, in turn, will find their own friends to participate and I can go and meet with them all in one place. So it takes spread-a-word, it's definitely a process. These people are not easy to find but that's because they're out there and they're busy. They're working or they're actively exercising and playing golf and keeping a very busy schedule. We have a hard time reaching the ones that call in because they are so busy.

CAVANAUGH: Well, I've just been told that if you do think that you or someone you know could be a participant in this study, you can find the information at KPBS.org/TheseDays. I want to thank you both so much for talking about this today. Dr. Eric Topol, Director of Scripps Genomic Medicine, heading up the "Wellderly Study." Dr. Topol, thank you so much.

DR. TOPOL: Oh, we want to thank you and KPBS for helping us along the way. We wouldn't have been able to get already 600 people without tremendous support that you've provided.

CAVANAUGH: Oh, you're welcome. That's nice. And Sarah Topol is the Clinical Trials Coordinator of the "Wellderly Study." Thank you.

SARAH TOPOL: Thank you very much.

CAVANAUGH: For more information about that study, as I said, go to KPBS.org/TheseDays. You're listening to These Days on KPBS.