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S.D. Scientists Close to Figuring Out Genetic Secrets of Good Health

Envision San Diego & KPBS Special Report

— Natalie Nestadt: I’m 80 years old and I think I attribute everything to genes, just good genes.

Forrest Adams: Longevity’s not for sissies.

George Dehnel: The human body is a powerful thing. It can take incredible abuse and still you might say, come up smiling. In our case, come up living.

Project Envision San Diego

Envision SD: The Aging Code

Web movie: Envision SD: The Aging Code

Above: Envision San Diego special: The Aging Code

That’s George Dehnel. He’s one of four San Diego seniors you’re going to meet tonight. They are part of a very special population.

Hello everyone, I’m Joanne Faryon. Welcome to tonight’s Envision special, The Aging Code. We are going to explore the secret to a long and healthy life. A secret that may be locked away in our genetic code.

San Diego scientists are close to figuring out why our bodies age and why old age is the leading cause of disease. Tonight, you’ll meet those scientists and you will get to know some people who are remarkably healthy for their age. They are the subjects of the first genomics study of its kind in the world.

Let’s start with George Dehnel. Before I tell you how old George is, watch him ride his bike. And now, get a closer look at his face. There’s barely a wrinkle. George Dehnel is 82 years old.

George: I got a few aches and pains in the hands particularly, little bit of knee thing, not very much, but basically I’ve been pretty much the same.

Just how George has been able to stay pretty much the same all his life is the subject of a nationwide study into the genetics of the so-called Wellderly – that is people 80 years and older with no history of chronic disease.

George: And every morning and night I do 80 to 100 pushups too just to kind of make me think I’m not as old as my birth certificate tells me I am.

Scientists believe if they can figure out what’s keeping George this healthy, this long, they could prevent age related disease in the general population.

And that could have a dramatic effect on how long we live.

A baby born today has an average life expectancy of 77 years. That same baby, born 100 years ago would have only lived to be 50.

The science of aging is advancing so rapidly these days – this baby, in her lifetime, could nearly double her expected life span.

Scientists now know that aging healthy and living long is not just determined by how we live, it’s programmed in our genetic code.

Dr. Andrew Dillin: In fifty years will we see the first person living until 150, I think it’s on the scope, I don’t know it will happen but I think the possibility is definitely there.

Sarah Topol: You look great.

83-year-old B is the newest enrollee into the Wellderly study.

Sarah: You’re okay with the stairs I imagine.

She’s a triathlete, cycling more than 20 miles routinely and swimming several mornings a week – in the ocean.

B’s blood is taken and her DNA is going to be studied.

Those in the Wellderly Study must be 80 years or older with no history of major or chronic disease such as cancer or diabetes.

This study is the brainchild of Dr. Eric Topol, chief of Genomic Medicine at Scripps Health.

Joanne: How many people in your study right now?

Topol is focusing his work on healthy people, old healthy people and their genes. He plans to enroll 1000 people into the study. So far, 600 have contributed blood and saliva samples.

Dr.Eric Topol: What we know already is people in the Wellderly group, they have bad genes. They have genes for Alzheimer’s, genes for heart attack, cancer and other illnesses, but they don’t get these diseases, and a lot of them don’t practice healthy lifestyles.

Topol believes people who live disease free so long, must have some kind of genetic protection.

Dr. Topol: We have some of them that are in their late 90’s who still smoke. So this is not just a lifestyle story. There is genetic inheritability that accounts for this so if we can understand what are the genes for the modifiers that titrate the risk, that cancel out this susceptibility to diseases wouldn’t that be exciting?

Topol isn’t sure whether he’s looking for a single longevity gene or a series of genetic mutations that protect against specific diseases. With 30,000 genes in the human genome, Topol is navigating a vast and complex landscape with the genetic code as his compass. In the end, he’s embarking on a journey not knowing whether his destination even exists.

We spent time with three of the subjects enrolled in the Wellderly study. You’ve already met George Dehnel. There’s also Dr. Forrest and Natalie Nestadt. Natalie is 80 years old. And she’s a smoker.

Natalie: I don’t have anything in particular, any notes to tell you. I did mention my grandparents came from Lithuania. They were strong healthy people. My dad was a healthy man and that’s obviously what’s happened to me. I just got their genes.”

Joanne: You smoke?

Natalie: Yep.

Natalie: No, I haven’t smoked for 80 years, nearly…65 maybe. 61 years possibly, but I’m not a chain smoker. I have my ten, 12 a day.

Natalie, her husband Stanley and four of their five children emigrated from South Africa to the United States more than 20 years ago after Stanley retired.

Photos of their past life show a big family who went to the beach often and traveled.

There’s Natalie with her thick brown hair.

Hair that stayed thick and brown until Natalie was 75.

Natalie: It just fell out. I had thick lovely beautiful hair. Day by day it came out in clumps, I was virtually bald.

But it grew back. Thick and curly and grey. She’s still not sure why.

Natalie also has good vision. She only uses reading glasses. She stills drives, sometimes to the casino. She bakes. And she travels.

Natalie: I’m going to Israel in June. I’m going to Alaska in July. I’m hoping to go to South Africa next year to my daughter. And travel is a great thing. I think that’s what’s very important as you get older.

And she’s been married to Stanley for 59 years.

Natalie: We are definitely the kind of people who you would say opposites attract because there is nothing we both like the same; food, where we’re going to go on holiday…

Natalie says she does not live a particularly healthy lifestyle.

Her exercise is marching up and down these stairs.

She eats whatever she wants.

Natalie: We really are going to Home Buffet for dinner tonight.

Stan: Just the two of us doesn’t pay to cook and they make the best meat loaf there.

And of course, there’s the smoking.

Joanne: Why not stop smoking? Maybe you’ll live 20 more years instead of 10 more.

Natalie: No, I wouldn’t like to live 20 more years. I couldn’t imagine being 100. I would hate to be in a wheelchair or hate to be in one of these assisted facility. No. I wouldn’t like another 20 years.

She would however want another 10 healthy years. But she believes that will not be up to her – it will be up to her genes.

Natalie: I was at the Los Angeles station one time and there were two young girls in front of me and I asked them if I could lean on their trolley, and they said to me, “How old are you?” And I said, “I’m 79.” And they said, “How come you look so good?” I said, “It must be my genes.” And they obviously didn’t know what genes, and they looked, like it was denim or something. They don’t know what genes are, they think you’re stupid, must be my genes…

Forrest Adams: I’m sure that I will have a number of genes that protect me from all sorts of infectious diseases.

Dr. Forrest Adams will be 90 years old in a few months.

He doesn’t smoke, rarely drinks and eats a healthy diet.

And as you can see, he exercises.

But he believes lifestyle has little to do with his good health.

Forrest: I’ve arrived at the conclusion the majority, 90 to 95 percent, of man’s medical illnesses are determined genetically in a sense we’re predestined to get certain things, like Alzheimer’s, Parkinson’s disease, heart disease…

Forrest is a descendant of John Quincy Adams, sixth president, a man who lived to be 81, a great feat back in the eighteen hundreds. Forrest’s grandparents and great grandparents all lived into their eighties and nineties.

Spend some time with Dr. Forrest Adams and it’s apparent he is a man of science. A pediatrician, cardiologist and researcher, he has spent a lifetime solving problems.

Joanne: It sounds like you could go back into the lab today. This is what excites you.

Forrest: I would if somebody asked me.

In the meantime, he’s not waiting around for an invitation. He’s been researching his new project.

Forrest: Then I want them to get my stem cells and put them in liquid nitrogen and save those.

Adams believes so much in the healing power of his genes, he’s arranging to have his stem cells harvested and frozen while he’s still alive.

Joanne: If you want your stem cells frozen then you want this long life for other people.

Forrest: Exactly.

Joanne: Why do you want this long life for other people?

Forrest: I don’t say they need to live until they’re 100 or 120. Longevity’s not for sissies. As one deteriorates, what you perceived you were when you’re 20 is no longer that way. All you got do is look at the commercials on television. It’s about women’s health thing and everything they’re selling for the face and the skin. They’re talking about 20 year olds. They’re not talking about 50 year olds or 70 year old women. That part you don’t look forward to. On the other hand, for people who are getting things that possibly could be prevented or cured, in the case of stem cells prevented.

George Dehnel: I just grind these things up, sesame, flax grind them up in here into a powder.”

82 year old George Dehnel isn’t so convinced he can rely only on his good genes.

Joanne: And this tastes good to you?

George: Yeah, it tastes pretty good, you’d be surprised.

Joanne: If you didn’t do any of this, if you didn’t eat this way and exercise, do you think you’d look and feel the way you look and feel right now?”

George: Absolutely not.

He eats chicken and greens for breakfast. He makes his own roughage concoction with these grains, blends a smoothie for lunch and eats oatmeal for dinner.

He doesn’t smoke, rarely drinks and does vigorous exercise every day.

George: I used to think, “George, if you do all these things right, you’re probably going to be healthy and happy and active right up to the day you die.” And I’m beginning to realize this is not going to be this way, that the body ages and the hands get sore and you can’t do all the things with as much strength and quickness and coordination like you use to do. So aging is a problem for me in the sense that I expect it to be perfect forever and then croak. And it’s not going to be that way.

But George may come as close to perfect as he can. He still sits in his rocker like a young man and moves around his kitchen like a teenager showing off his latest gadget, his Cuisinart.

George is right, though, eventually age catches up to everyone.

Our bodies go through a typical aging process. Forget about wrinkles. Think about the systems in your body. Your heart, your digestive system, your brain. They all lose function over time. Let’s take a look at the normal aging process.

For men, risk of heart disease begins at 45, for women 55. Forty percent of deaths in people 65 and older are heart related, making age the biggest risk factor for heart disease.

Eighty percent of cancer is diagnosed at 55 or older.

Once you reach 65, you are now at risk for Alzheimer’s, and every five years that risk doubles.

By age 75, you have a one in three chance of losing your vision to macular degeneration, and you’ll almost surely have hearing loss.

Add to that a long list of age related ailments like arthritis and osteoporosis. Your skin will also get thinner, your mouth drier, even your digestive system slows down.

Joanne: When do we start seeing these age onset related diseases, when do they start happening is it forties, fifties, sixties? It’s in your forties?

Dr. Dillin: Forties.

Dr. Andrew Dillin is a researcher at Salk Institute.

Dillin: Fifteen years ago it was argued it was environmental and there was very little genetics involved. So now that we’ve actually found genes that we can manipulate and make an animal live twice as long, it’s really opened up the door. There are genes that play a role in it.

Dillin uses a tiny worm to study the aging process.

He believes if scientists can control aging, they can control the onset of age related disease.

Dillin: I have no interest in making people live longer. I want to have them live healthier a longer period of time and so that’s the ultimate goal. To not increase life span but increase health span.

But the two may go hand in hand. At least that’s what Dillin’s research has shown so far.

This is video of some of Dillin’s experimental worms. Researchers injected some of the worms with a protein associated with Alzheimer’s disease. They were also able to reverse the effects of the disease. In other words, cure the worm of Alzheimer’s. But the cure had a side effect, it doubled the lifespan of the worm.

Dillin: We don’t want to increase the bad years of your life span. We want to increase the youthful period of your life span and ideally we would not like to increase lifespan at all, but just the youthful period. So when you’re 90, you felt like you were when you were 60, but you’re not going to live until 150 years old, you’re going to live to be 100 years old. That would be the ultimate goal, but so far, we haven’t been unable to uncouple that. So every time we increase the health span we increase his lifespan as well, so we haven’t figured out how to uncouple those two events. So it may be a side effect that comes from this research, you might actually increase life span by 50 years and health span by the same time.

Dr. Topol: The Alzheimer’s, the apoe3, you don’t have it. This is also for long life. This is the most important of all the whole scan right there. You are so lucky. You’ll be around a long time.”

Back in Eric Topol’s lab, Topol’s learned his daughter Sara, who is also a nurse working on his study, doesn’t have the Alzheimer’s gene, something he believes may be linked to the longevity gene.

And while there is excitement at the prospect of his daughter living a long life, Topol says the real goal of his research is to increase health span and not life span.

Topol: What if we start to learn what keeps people healthy? And if we can learn that wouldn’t that be a much better way to get the information we need to enable health over the years ahead?

Topol believes environment does influence how one ages, but he’s excited at the prospect of discovering a genetic mutation that buys some people protection against age onset disease. He says if he can find that, researchers can eventually inoculate the rest of the population.

Topol: It could be a vaccine. It could be a pill.

Dillin: If you know of genes that control aging and they would be targeted as pharmaceuticals, you can imagine that somewhere down the road, someone is going to develop a drug that will possibly change the aging process.

Topol’s lab will begin sequencing the genes of the hundreds of Wellderly subjects in the next several months, but so far, he’s been able to put together a body type of the average person enrolled in the study.

Here she is: female, short average metabolism, and lean., a slower than

Topol: The short stature story, that’s really interesting, because in all species, dogs, elephants, all species, the shorter that the species is, the more long life and health that person is endowed with. The other one that was a surprise was about thyroid disease. And Sara Topol has noted there have been many people in this study that have a history of a low thyroid. So the question is, does that protect people? Does that slow down the process? Is there something inborn? Should we all be walking around a little hypothyroid, to make us healthier?

B: I’m happy I have found love in my life at 76 and that makes me happy.

There’s something else, not so scientific that Sara Topol has noticed about the people in the study. They have a positive attitude toward life. They want to live.

According to the U.S. Census Bureau, the so called oldest old – people over 75 – are among the fastest growing populations in the world.

In 2020, American baby boomers will add to this population explosion as they begin to turn 75.

They will consume proportionally greater amounts of healthcare than younger populations.

The Census bureau warns “the rapid growth of this population segment will force nations to grapple with issues of long-term care, institutionalization, and pension reform.”

Dr. Larry Hinman: If they could fifty years to my life in my forties, I’d really be happy. If they add it in my eighties, I’m less convinced this would be highly desirable.

Lawrence Hinman is a philosophy professor at the University of San Diego. He says prolonging a healthy life would be a wonderful thing, provided society was prepared for a growing older population.

Hinman: I think one of the things that’s important from an ethical point of view is that this has to come as part of a much larger package. Otherwise we’re going to have disaster. Think about social security. You think it’s in trouble now. Imagine what it would be like if people retire at their current age and then draw social security for the next 60 years.

There’s something else we must consider. Will a society in search of eternal youth begin to value age?

And what happens when you have the longevity gene but those around you don’t?

Forrest Adams is an atheist. For him, there is no religious comfort in death.

Joanne: So do you think about death?

Forrest: Do I think about it? All the time. Yeah. One of the offshoots of that is I have no fear of dying but I think one of the reasons people have such strong religious beliefs is they’re fearful of dying and religion helps provide a cushion.

Joanne: You think about it all the time. Is it because you’re 90 that you think about it?

Forrest: I would say it’s more because most of my friends are dying and I now have a folder of the obituaries from people that I worked with who have since died.

George: Yeah I think about dying a lot. And I don’t have any idea what it’s going to be. Probably if I knew I’d commit suicide. I don’t know. That’s all I can say about that.

Joanne: Do you believe in an afterlife?

Natalie: Do I? I don’t know. I don’t think so. I think when you’re dead you’re dead.

You mean, do you come back as something else or no? I’m not spiritually inclined that I expect someone to come and visit me in my dreams or something. You know you dream about your parents or an incident or something like that but it’s not something that you read books where you think someone’s looking after you or something, I don’t think so.

George: I believe in an afterlife only that I’m going to have my ashes thrown in the Pacific Ocean and I think it’s marvelous. I love the thought of becoming a dolphin or a fish or a whale or a piece of seaweed or a little plankton floating in the Pacific Ocean, but in the afterlife in the Christian sense? Absolutely not. No.

Hinman: I know my mother who last year passed away, she was almost 99, and she loved life, but she was ready. Her husband, my dad, had died 10 years earlier. All her siblings had died more than a decade before that. She came from a family of seven other kids. All her friends from high school, the neighborhood had passed on and there was a loneliness and increasingly at the end there was a debility. She just died of old age, but there was very little coming into her world. It was hard to see. It was hard to hear it was hard to move. You want presumably, you don’t want to lengthen that by a couple of decades.

Topol: Most people, when you poll them, they’re not interested in living until they’re 110. They want to live to whatever age, but be healthy all the way through. So this concept of Wellderly, everybody wants to be in the Wellderly club. That’s what we’re really after. If we can keep people who otherwise very highly likely to develop a particular condition disease, if we can keep that in check, well, it may not make their life expectancy 100 plus but it may increase their quality of life and certainly if it was a serious condition it could increase their expectancy in some matter of time.

Joanne: How long do you want to live?

Forrest: As long it’s going the way it is right now, indefinitely.

Forrest Adams, a man of science, knows exactly how he will live forever. Not in an abstract afterlife, but in the here and now.

DNA, locked into each one of our chromosomes, is remarkably resilient. In fact, scientists uncovered the DNA of a prehistoric beetle trapped in amber more than 120 million years old.

Forrest: In a very philosophical sense my chromosomes are going to, the electrons are going to continue and that’s going to be me, it’s not going to be you, it’s not going to be anybody else, and that’s the way you live forever.”

The Wellderly Study is still accepting volunteers. If you are 80 or older and healthy, they want your DNA. To find out if you, a family member or loved one might qualify to volunteer for the study, call 1-800-SCRIPPS (1-800-727-4777), or e-mail wellderly@scrippshealth.org.

For KPBS and Envision San Diego, I’m Joanne Faryon. Thanks for watching.

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