Breakthrough (2015) s01e04 Episode Script
The Age of Aging
1 MAN: Are you feeling tired and rundown? Do you drag yourself out of bed in the morning? Does life seem hardly worth living? Then, friends, give me your undivided attention.
MAN: When the bloom is off the rose MAN: It's fix up, paint up, patch up.
You got to stay young.
MAN: It is a tonic, an elixir, to purge the body and lift the spirits.
WOMAN: Tell me, how great is the power of this liquid? MAN: For a long time people have been seeking the fountain of youth.
With the belief that there's some magical substance that will slow aging.
NEWSCASTER: Scientists say the fountain of youth could lie in MAN: Strawberries.
MAN: Red wine.
MAN: Omega-3 fatty acids.
MAN: Plain, old vitamin C.
OPIE: It's just another commercial.
AUNT BEE: I'll take two! MAN: The difference now is we have a really solid science which is pushing forward into the future, and it is uncovering mechanisms which modulate aging.
MAN: We know it's possible, at least in mice.
So it means it should be possible in humans if we put our minds to it.
MAN: If we can slow aging in humans just a little bit, the impact, it is monumental.
People can be older and feel young.
It takes you 70 years to become 50.
But enough advances have been made in aging science to lead us to believe it's plausible, it's possible, it's been done for other species, and there's every reason to believe it could be done in us.
WOMAN: We know that aging is modifiable.
MAN: The future is taking the biology that we've now developed and applying it to humans.
MAN: This would be the most important medical intervention in the modern era.
An ability to slow aging.
NARRATOR: In New York City in early 2015, a group of experts on the biology and demography of aging gather to discuss an ambitious new plan to change the way we think about aging and disease.
NIR BARZILAI: I'm going to ask you, how do we change the world? NARRATOR: Over the next several months, they will unveil a pioneering study designed to convince the world, and critically, the Food and Drug Administration, to recognize an entirely new category of drugs for the purpose of slowing aging in humans.
JAY OLSHANSKY: When you go to the FDA to seek approval, you're seeking approval for a treatment of a disease, right? What we're doing is we're seeking approval for a treatment of all diseases.
BARZILAI: This idea that we can delay aging is a new idea.
And the recognition that aging is part of every disease is not really well-established.
STEPHANIE LEDERMAN: When there's an article about we could cure cancer, nobody says, 'Oh, it's such hype.
' They believe in it, but as soon as you talk about aging, then it's snake oil or what are you trying to do, or there's too many old people.
Thousands of things come forth.
BARZILAI: We need to convince a lot of other people of what we're doing.
We need to convince the public.
LEDERMAN: Will it happen in our lifetime? BARZILAI: We need to convince the press.
OLSHANSKY: Come in, because there may be dangers.
BARZILAI: We need to convince the politicians.
JOAN MANNICK: You're setting the bar so high.
BARZILAI: We need to convince the FDA.
Because we're sure of the science.
We're sure of the promise, but the time is now.
NARRATOR: Time has flown for baby boomers like me.
In the next 15 years, the last of us will reach the age of 65.
Between now and 2050, the number of people over 65 in the United States is expected to almost double.
Worldwide, it will nearly triple.
Older people will make up an increasing share of the total population.
We can expect to see more of our parents and grandparents out of the workforce, battling cancer, heart disease, diabetes, frailty, and Alzheimer's, with dire consequences for our economies and health care systems.
OLSHANSKY: We need to demonstrate that this research is worth doing and that the consequences would be a public health revolution.
MANNICK: That's why we need you guys.
BARZILAI: That's why we need to do this study.
MANNICK: Right.
LEDERMAN: They have to see proof that this can be done.
And that's what we're trying to do, is give them that proof.
OLSHANSKY: What happens if we don't succeed? BARZILAI: We'll die trying! [laughter.]
NARRATOR: Why would they think they can modify the aging process? Only recently have mainstream scientists agreed that it might even be possible.
LAURA DEMING: I never went to school.
I taught myself everything from calculus to biology.
I knew that I wanted to be a scientist, like, from day one.
That was a given, it was just what field? And at first I thought, you know, cancer was the most important problem, and then I realized, no, aging is the most important problem.
We should go focus on that.
And then the rest of it was just kind of trying to figure out how to be a biologist.
And when I was 11, I emailed a woman called Cynthia Kenyon and asked if I could come see her lab.
CYNTHIA KENYON: Dear Professor Kenyon, I am 11 years old.
DEMING: And ever since I was six, have developed an acute interest in the study of the extension of human life.
KENYON: And I was wondering if I could meet you to ask some questions about a career in biology.
DEMING: Of course what I really meant was I want to come work in your lab, but that was the best way to say it.
I imagined Cynthia's life was this kind of whirlwind of being a superhero.
Staying up late at night and sleeping in the lab and making discoveries, like, having eureka moments continuously, and loving life.
Meeting her for the first time, it was like meeting the person that I always wanted to be.
KENYON: This is this one that you saw on the Internet.
DEMING: Oh, that's amazing.
KENYON: I'm sure it's the one.
This is about the time that we were making our discoveries.
None of these people worked on aging, though.
They were all working on other projects.
And it was a long time till anyone would work on aging, because people were afraid of it.
People, for years, had been comparing old and young.
Then they would have theories for why aging took place.
But there was no mechanism, like this dial, that you could turn up or down and change the rate of aging.
So I was studying worms, and my plan was to just change genes at random and look for worm mutants that live longer.
We taped worms for five minutes every day for their whole lives.
I had these little petri dishes.
One had normal worms, old, and the other had the mutant ones, moving around.
And I thought, I want to be those worms.
DEMING: Cynthia's fundamental finding was that you could change a single gene in a worm and have that worm live twice as long as normal.
GORDON LITHGOW: That was an incredible moment.
And frankly, people didn't believe it.
You could change a single gene and see a 70%, 75% increase in longevity.
SIMON MELOV: And that started to propel this idea that maybe aging was just like any other biological phenomenon.
Maybe you could manipulate it through the power of genetics.
KENYON: And right about 1998 or so several labs working on fruit flies showed that if you change the same gene, they live longer.
LITHGOW: Then people started doing this with chemical compounds, showing similar effects.
MELOV: That movement slowly started to expand and proliferate into other disciplines.
KENYON: Several labs found that making similar gene changes could also extend the lifespan of mice.
LITHGOW: We know of hundreds of genes now that when altered, changed the lifespan.
So aging itself is modifiable.
The question now is, is it modifiable in us? NARRATOR: In 1900, average lifespan was about 50 years.
A child born today can expect to live to be almost 80.
Astonishing progress in science and medicine have given us considerably longer lives, but as more of us live to an old age, we are facing protracted periods of sickness and decline.
BARZILAI: If we achieve long life, and the price is that we are sick for more of it, we're not really doing very well.
So how can we achieve longer, but healthier life? Centenarians are a clue.
They're a clue for us of how to live healthier as we live longer.
NARRATOR: What if we were vibrant up until the very end, and then passed away after a short period of sickness? Nir Barzilai has been studying a group of exceptionally healthy 100-year-olds or centenarians.
BARZILAI: Hi, Milton.
MILTON NUSSDORF: You're like the mailman, you're on the button.
BARZILAI: So nice meeting you.
How are you? NARRATOR: He believes they're a model for how we can all age.
NUSSDORF: Come on in, fellas.
RITA GOLOMB: Hello.
BARZILAI: Hello! GOLOMB: Oh, hi! How are, how are you? BARZILAI: How are you? One of the interesting thing with those centenarians is to see how they interact with the environment.
And we thought, hey, maybe they do all the right things.
Do you eat something special? Do you GOLOMB: No, I try to keep a healthy diet.
BARZILAI: What about exercise? NUSSDORF: Exercise.
I walk about a quarter of a mile for breakfast.
GOLOMB: I swam every day.
NUSSDORF: So my body has always been, uh, activated.
BARZILAI: And when you look at the population, you find almost the opposite.
NUSSDORF: I go every, just about every afternoon to Dunkin' Donut.
And I have coffee there and a Boston Kreme, that sort of thing.
BARZILAI: Your eating habits are not necessarily healthy, right? NUSSDORF: That's true.
GOLOMB: I smoked for 50, so, 50 years.
BARZILAI: 50% of them are obese.
50% of them do not exercise.
60% of the men and 30% of the women are smoking.
So it's in spite of all that, that they have some protection that allows them easily to get to age 100.
What we do find that they have is genes that are protecting them against anything that's thrown their way.
Those are individual cells that have mutations we think are associated with longevity.
And we follow what those mutations are doing to the cell.
What happens when you put the cells into a hostile environment? The reason we're looking for those mutations is that we think that those mutations will slow the rate of aging.
NARRATOR: Barzilai believes, from a biological perspective, his centenarians are aging slower than the rest of us.
His plan is to prove that medications can make us all age more like them.
BARZILAI: When you do genetic study, the public thinks that we need genetic treatment for those diseases, but no, we cannot change your genes, so that you become 100 years old.
But we can design medications based on our knowledge that will interfere with this pathway, and interact, intervene and delay the effects of aging.
MARTHA KAMIN: Well, I remember I gave him his first camera.
ED KAMIN: It's not easy to be the wife of a persistent photographer.
Martha studying in college.
M.
KAMIN: Ed asked me if I would like to go down to the cafeteria.
That was our first date.
E.
KAMIN: That was taken by a relative at our wedding.
Martha's so anxious to get married on this day.
M.
KAMIN: Well, I had been waiting seven years.
[laughs.]
Oh, that's our son, Thomas, who was 4'13 when he came home from the hospital.
He was smaller than Dad's shoe.
Oh, this one is a little bit more typical.
[laughs.]
E.
KAMIN: Ahh, I don't know if it's typical, but there's seven children, and everybody's happy, everybody's smiling.
This is back in the mid '70s when Martha was climbing mountains before her heart disease began to catch up with her.
M.
KAMIN: I liked the fact that I got up there before you and before Tom and before Mark.
[laughs.]
E.
KAMIN: This picture was taken with a self-timer.
It's a good photograph.
Two old people, hand in hand, going down into the uncertain future into the dark woods.
But it's as artificial as can be because of the self-timer, tripod, I ran, got into position.
M.
KAMIN: Turned right around.
E.
KAMIN: Turned around and got the dickens out of there.
[laughs.]
NARRATOR: Dr.
Ed Kamin and his wife Martha live at the world famous Mayo Clinic's retirement community after seven children and a long career in medicine.
M.
KAMIN: Well, I think that every day is a gift, and I hope that I can have that same attitude when perhaps I'm not as fortunate as I am right now.
You know, but E.
KAMIN: You mean when your batteries run down in your skull? [laughs.]
[knock knock.]
SARAH CRANE: Hello! I am Dr.
Crane, Sarah Crane.
E.
KAMIN: Ed Kamin.
Used to be a doctor.
JIM KIRKLAND: Jim Kirkland.
How do you do, sir? E.
KAMIN: Hi.
CRANE: Geriatrics is extremely complex medicine in the sense of multiple diseases going at the same time.
What are the issues that you're dealing with from a health standpoint right now? M.
KAMIN: I have osteoporosis.
E.
KAMIN: Five hip surgeries.
Breast cancer.
M.
KAMIN: Aortic stenosis.
CRANE: Okay.
E.
KAMIN: Martha now is the proud owner of four stents in her coronary arteries.
I think the record is 73, Martha, so you've got a long way to go.
M.
KAMIN: Oh, good.
KIRKLAND: In medicine, we've come up to the point where we're making incremental gains.
If we cured cancer, if we cured Alzheimer's disease, if we cured heart attacks and strokes, we would still die of something else a few months or a couple of years later.
That's because fundamental aging processes predispose to these diseases and conditions.
CRANE: We're beginning to hit a ceiling of healthy aging, because we're really great at treating diseases.
We are not so good at treating aging.
The burden of illness and of debility within the community is going up.
M.
KAMIN: Walking from here over to the clinic is a little bit beyond me.
CRANE: Mm-hmm.
E.
KAMIN: Primarily for the orthopedic problems.
But the heart problems are there, too.
CRANE: Most people don't really want to spend their last five years visiting us every day, or going to cardiologists every day or being in the hospitals or those types of things.
That's not quality of life at this point, so to be maintaining your functional status for as long as possible is the ideal.
You get to enjoy your grandkids, travel around the world, do all the things you want to do.
And then one day you don't wake up.
NARRATOR: The goal is to make us less sick at the end of our lives.
Researchers at the Buck Institute in Northern California are looking for ways to prevent the many diseases associated with aging by slowing the aging process itself.
To discover drugs that will one day increase health in human beings, researchers start much lower on the evolutionary ladder with single-cell organisms.
BRIAN KENNEDY: The nice thing about yeast is that we can keep billions of them in the laboratory very easily.
If we're testing drugs, we can look at 20 or 30 drugs in a single week looking at yeast cells.
It's so fast.
NARRATOR: If a chemical compound works in yeast, they test it in more complex organisms.
Conditions seen in aging animals like worms have surprising similarities to serious diseases seen in aging humans.
LITHGOW: We've shown recently that during normal aging in worms, there is an accumulation of insoluble proteins, and we believe this material is toxic.
And lo and behold, that's exactly what many people in the Alzheimer's field have been thinking about for years.
The sticky stuff that we find in the brains of Alzheimer's patients.
The compounds that extend lifespan also reduce Alzheimer's disease proteins, Parkinson's disease proteins.
If you target an aging process and you slow down aging, then you slow down all the diseases in the pathology of aging as well.
MELOV: Once we have identified from potentially screening thousands of compounds, a hit, we consider whether or not to apply that in a laboratory mouse.
NARRATOR: The dreaded fall, the broken hip, fragile bones are feared by the elderly.
MELOV: You get a fracture, you go to hospital.
You're more likely to go in a downward spiral and not come out.
NARRATOR: Using computerized tomography, high resolution images of aging mice help identify compounds that could slow the degeneration of bones.
To develop new drug therapies for aging, we need a more complete picture of how those therapies affect cells.
At GE's Global Research Center, Dr.
Fiona Ginty has found a way to image human tissue in unprecedented detail.
FIONA GINTY: We've developed a new technology here at the research center that allows us to see multiple proteins within a tissue sample.
NARRATOR: Using dyes to highlight individual proteins, she can create a sophisticated map of the quantity and location of those proteins in a tissue sample.
GINTY: By doing an analysis of all the proteins, you discover how those cells are responding to therapies.
Ultimately, those are the complete picture of biology and how in turn longevity is influenced.
NARRATOR: At the Mayo Clinic, Dr.
Jim Kirkland and his team are focused on taming another mechanism of aging, senescent cells.
KIRKLAND: Senescence is a process where cells that normally divide lose their ability to divide.
They become resistant to dying, and they produce things that kill the cells around them.
We discovered drugs that we call senolytic drugs.
We found they cleared senescent cells in mice.
This is seven days after the last dose of the drugs.
By targeting senescent cells, we can delay or even prevent or alleviate age-related diseases.
NARRATOR: To measure the effect of getting rid of these senescent cells, Dr.
Kirkland sends his mice to the gym.
KIRKLAND: One of the things that decreases with aging is their endurance on a treadmill.
So we gave senolytic drugs to very old mice.
We gave them to mice that had had difficulty with their walking.
We found that up to seven months after just one dose of these drugs by mouth, they were walking as well as healthy mice.
NARRATOR: In an increasing number of labs around the world, scientists have shown that they can improve health and longevity with drugs that treat fundamental aging processes.
KIRKLAND: We can do a lot of this now in mice.
The push now is to test can we really translate these things into people? LITHGOW: We're beginning to look at normal aging processes and one by one tick them off and say, 'Ah, that's why this disease is associated with aging.
' MELOV: Aging is a tractable phenomenon.
It's something you can study.
It's something you can manipulate.
That's a very exciting time to be in human history.
You're talking about developing a therapy for a biological phenomenon which is universal and gives rise to all of these diseases with time.
And if you've got a therapy for this thing, these diseases just go away.
DEMING: I love science.
That's where I come from is from just thinking that science is the place that you should start.
But I think that the gap is that everyone else who is like me, who loves science, just stays in science.
When I was 14, I applied to MIT.
And so I was there for two years, but then right around the end of my sophomore year had this big moment.
I'd been working on aging science now for, like, six years and just, you know, nothing had kind of happened, and it was all still in the research stage, and there were literally zero drugs out there.
So I dropped out of MIT, came to Silicon Valley and started a venture capital fund.
And that specific goal of having a drug in people in 10 years, I think would be impossible to accomplish by just staying in academia.
And so the reason that I left was to just work on that and making that process happen.
I'm on my way to see Nir Barzilai, who is at the Albert Einstein College of Medicine, because I've heard that he and some of his colleagues are looking into ways to get the FDA to take aging more seriously as an indication.
NARRATOR: It's not possible to create an FDA-approved drug for aging because they simply don't recognize that such a treatment exists.
BARZILAI: There are several drugs that are in human use, that we have been testing, and we show that they slow aging in a variety of animal models.
NARRATOR: Metformin, a widely used generic diabetes drug, has been shown to delay aging in animals.
Early observational data suggest it may do the same in people.
BARZILAI: Why metformin? Because we have great preliminary data.
There was a study from the UK.
It took people with early diabetes, just diagnosed, and treated them either with metformin or several other drugs.
This is what made me so excited.
They took 78,000 people that were just put on metformin, and they matched them with 78,000 people that don't have diabetes.
All the people with metformin have diabetes.
DEMING: Yup.
BARZILAI: And the cool thing is that people on metformin that had diabetes, they were more obese, they had more diseases to start with, had 17% less mortality than the controls without diabetes and without diseases.
DEMING: So you must have just looked at that and said, 'We have to do this.
' BARZILAI: Right.
The summary of what I'm telling you is that we're going to take people between 70 and 80 years old, and we're going to monitor those four things where we have preliminary data.
Prevention of diabetes, prevention of MCI and Alzheimer's, prevention of cancer, prevention of dementia, and prevention of mortality.
NARRATOR: Dr.
Barzilai and his colleagues say that metformin may not be the ultimate drug, but the important thing is to get the FDA to accept the idea of a drug that slows aging.
BARZILAI: So we take metformin, really as a tool, because metformin is generic, is cheap, is safe.
People have been using it for 60 years.
And we want to treat a bunch of people and show the FDA that we're going to slow the rate of aging.
DEMING: When I first came out to Silicon Valley, I was young and naive and I thought, oh, um, you know, if we can just show people that the science is good, and that the scientists believe this is worth doing, that's what will make them excited about aging.
And then I talked to this venture capitalist, one of the first people that I talked to who said, 'The only that I care about is what the FDA thinks.
' And that's it.
People in biotech will just sit in a room and be like, 'Okay, what should we fund?' And, and should we fund diabetes or cancer or, you know, and all these list of medications that they can put, you know, billions of capital into.
And aging is never on that list, and it's never on the list because the FDA does not see aging as a thing for which you can do a clinical trial.
BARZILAI: If we succeed with the FDA, we're going to change health care as we know it, because all those biotechs, pharmaceuticals will go in and think that way, and they'll develop drugs that will get better and better as they've done for other diseases.
DEMING: If you were to successfully run this trial, that would change everything about what I do, what most people in the venture capital field, I mean, that would be incredible for the field as a whole.
NARRATOR: Why do we think about treating sickness in terms of individual diseases? Most of the gains in life expectancy in the 20th century were due to our success in treating infectious diseases like pneumonia, flu, and tuberculosis.
Demographer Jay Olshansky believes that we are the victims of this success.
OLSHANSKY: The difficulty is a conceptual way of thinking, which is one disease at a time as they crop up.
It's the old infectious disease model applied to chronic fatal diseases.
The infectious disease model was what existed prior to 1950.
As soon as you experience an infectious disease, you go to your doctor, your doctor treats you, pushes you back out the door.
Get the next infectious disease, you go back to your doctor.
The doctor treats you, pushes you out the door.
So what are we doing? We're applying this infectious disease model to chronic fatal diseases.
Heart disease, cancer, stroke, and Alzheimer's.
We've built all of these institutes, the FDA and others, around the idea that somehow all of these diseases are independent of each other.
The cure for cancer would yield about a three-and-a-half-year increase in life expectancy.
But if you slow aging, just a little bit, you influence all of the fatal and disabling diseases at once.
So the impact is far greater.
They're not used to attacking multiple diseases simultaneously.
So somehow we have to convince the FDA and others involved that if we, if we go after the underlying risk factor for all of the diseases, we'll call that aging, we can influence all diseases at once.
That's what we're trying to achieve.
NEWSCASTER: Now to Dr.
Ezekiel Emanuel, who is NEWSCASTER: A trained oncologist, Dr.
Emanuel is Chair of the Department of Medical Ethics and Health Policy.
RACHEL MADDOW: He's a former special health advisor to the White House Office of Management NEWSCASTER: Dr.
Ezekiel Emanuel argues that the quality of human life begins to drop off by age 75.
He says that he will opt out of medical treatments and let nature take its course.
EZEKIEL EMANUEL: I think the people who are doing this aging research, for a lot of them, it's a puzzle.
They're in the puzzle.
They're trying to figure out the puzzle.
You know, for the rest of us, who are sort of watching it and want to consume it, we have this sort of techno-utopianism, we believe it'll be better in the future, we're gonna somehow fight death, we're gonna live totally healthy, and then we're gonna fall off at the end of a cliff.
That's not the way the world works.
So at 75, I'm going to stop doing medical treatments where the purpose of the medical treatment is to extend my life.
I'm not going to spend my time going from doctor to doctor.
And I think it's going to make my end of life more focused on the living than trying to do everything to get a few more weeks or months out of it.
I remember my dad as this bundle of energy and enthusiasm, and he had a tremendous drive and zest for life.
E.
EMANUEL: He was 74 years old, he had a heart attack.
And I think everyone will say since that time, he's not been the same.
E.
EMANUEL: When did you start that different life? After your heart attack.
B.
EMANUEL: Yeah.
E.
EMANUEL: It should have been all finished at 75.
E.
EMANUEL: We all end up dying.
And we need to confront that fact.
Why are you living? What makes your life meaningful? And how does that relate to living as long as possible? I don't think a meaningful life is about stacking up more years.
E.
EMANUEL: What else? You talk on the phone.
You harass your kids on the phone.
B.
EMANUEL: No.
E.
EMANUEL: Maybe it's born out of the fact that I'm an oncologist and we've been promising a cure to cancer since 1972.
It's now more than 40 years, and we still don't have that pill for cancer, maybe we're gonna be faster in that pill for, you know, no morbidity in our life.
Somehow, I'm a little skeptical about it.
And you have to, I think, plan your life on a reasonable basis.
And today, the reasonable basis is we're not gonna have that pill.
If that pill comes along and you get 10 extra years, great.
But I wouldn't bet your last nickel, and the most important thing, I wouldn't bet your own life, that that pill's gonna be there for you.
I was taking my blood pressure that my pulse rate was about 108.
And he said, 'Heavens to Betsy, how long has that been going on?' E.
KAMIN: Martha was having a heart attack as she was trying to get over the flu.
NARRATOR: In the wake of her heart attack, Martha, at the age of 90, must consider whether to have major surgery.
The decision is complicated by her chronic conditions.
E.
KAMIN: Martha has a severely narrowed aortic valve, and that's a major risk to Martha's health.
It's at the point where it's called critical.
A 50% mortality predicted in two years.
THOMAS JAEGER: I'd say a lot of people die of heart failure, related to aortic stenosis.
And that's not an easy road.
We're very good at treating symptoms.
And yet eventually your quality of life is kind of pulled out from under you.
PAUL McKIE: It's nice to meet you.
M.
KAMIN: Yes, same here.
McKIE: How are you doing? M.
KAMIN: Okay, I'm good.
I think I'm doing well.
McKIE: Great! Great.
When a person has a severely blocked valve, we think about opening up the valve or replacing the valve.
M.
KAMIN: Right.
McKIE: Any questions for me or concerns? E.
KAMIN: The frailty and the length of the convalescence, at age 90, that's gonna be a long convalescence.
M.
KAMIN: And the other thing is none of us like to lose our independence.
McKIE: Okay.
M.
KAMIN: I hate to think of him having to wait on me hand and foot.
[laughs.]
JAEGER: We can't kick this can down the road for a year, for instance.
If she waits a year or longer, then she'll probably have made a decision by default to say I'm just gonna let this take its course.
This is the best images of Martha's valve.
Those cusps of that valve should be opening completely.
CRANE: What we're seeing right now is something different.
The heart is stiff.
It's not that it's weak, it's just hardened and stiffened, and we have no medications for that.
I can't fix it.
I can't prevent it.
I can't keep it from getting worse.
It's a classic example of something that comes with aging that I can't fix.
E.
KAMIN: In my years of practice, I never found a patient who was feeling well, had accepted the infirmities of age, who said to me, 'Enough, I want to quit.
' Because it's wired into us that we want to continue living.
MAN: What if I told you there really is a fountain of youth? Would you believe me? MAN: Sign me up! NEWSCASTER: You want to get an edge on turning back the clock with just a few pills? Who doesn't? NEWSCASTER: Imagine this, you can live a healthy, vital, energetic life well past the age of 100.
NEWSCASTER: With just a few pills.
NEWSCASTER: It is possible NEWSCASTER: Remain.
NEWSCASTER: Younger.
NEWSCASTER: Vital.
NEWSCASTER: Vigorous.
NEWSCASTER: Planet Earth is a crowded place.
MAN: Trajectory is WOMAN: Six billion to seven billion.
MAN: People alive today may live a thousand years or more.
MELOV: There is this noise constantly, which is not surprising when you think about the subject matter.
The subject matter is our own mortality.
For thousands of years, we have had people prescribing cures for our own mortality.
NEWSCASTER: Some doctors prescribe human growth hormones.
MAN: Antioxidants.
BARZILAI: This is marketing, and people are reading that.
And people are concerned with their health and they're trying it.
NEWSCASTER: America's population is aging.
MAN: Very crowded.
NEWSCASTER: Humans are overpopulating the world.
NEWSCASTER: We're gonna have more people over the age of 60 than under the age of 15.
KENNEDY: The world is rapidly getting older.
There are not gonna be enough people working to pay for all the older people.
NEWSCASTER: It's very, very serious for the planet.
NEWSCASTER: There's a finite amount of resources.
NEWSCASTER: That means confronting a growing health crisis.
NEWSCASTER: In a finite world, you can't grow forever.
KIRKLAND: The bulk of morbidity, mortality, distress in the population, health costs, are related to these age-related chronic diseases that we're just seeing more and more of.
MELOV: But if we can really robustly develop therapeutics, which improve function with age KENNEDY: Then that grandparent is not being taken care of, but instead of that they're taking care of your kids.
They're contributing.
MELOV: People may work longer, productivity will be better.
NEWSCASTER: So you think there is someone alive today who could live thousands of years? OLSHANSKY: The immortalists are the ones who believe that we're gonna have radical increases in life expectancy up to 1,000 years, 5,000 years.
MAN: Exactly, I don't think there's any limit.
That there is nothing that would stop people intrinsically from living thousands of years.
KENYON: It's not really what the field is about right now.
It's so exciting we have things that slow down aging and affect diseases.
So now, let's get more of them, let's learn more about aging, and let's see what we can do for people right now.
OLSHANSKY: We have to constantly battle with this line of reasoning.
BARZILAI: How can we be heard when there is so much noise like that around us? If they can win support from the highest reaches of government, scientists believe they can change our nation's outlook on aging.
They meet with the ranking member of the Senate Aging Committee to make their case.
BARZILAI: So nice of you to meet with us.
CLAIRE McCASKILL: Of course.
BARZILAI: What people don't realize is we have found a way to intervene with aging, and these concepts have been proven in animals and is now going to be tested in humans.
The major risk for any one of the diseases is aging.
McCASKILL: Instead of thinking of it as an individual disease, thinking about it, okay, as we get older, this is what our bodies do, and we address that issue instead of, I've got to worry about diabetes, or I got to worry about a stroke, or I've got to worry about Alzheimer's? STEVEN AUSTAD: Yeah, what we've discovered is that basically, if we learn how to treat those underlying causes, we can delay all these diseases that kill and debilitate people as a group.
McCASKILL: People don't realize that just reducing adult onset of diabetes by a reasonable, modest percentage is enough to get us out of debt.
So I can imagine if we can do this across the board, just delaying slightly, and of course the train wreck that's coming, in all of our government programs is in fact the demographic bubble.
If we can get a handle on slowing the aging process, if we can actually do that, we are talking about a huge economic boon to this country.
OLSHANSKY: Every major public health advance in the 20th century had a champion.
Somebody who stood up and said I want this to happen, I'm gonna make it happen.
And we're hoping that sometime before the president leaves office, he raises this issue once again, considers it a global challenge.
McCASKILL: Well, I'll be glad to tell him.
OLSHANSKY: We would be delighted.
AUSTAD: We would love that.
McCASKILL: Yeah.
I will be glad to tell him.
OLSHANSKY: There's a lot of excitement in the field now, and we feel traction.
We can feel it.
We can sense that people are coming on board.
BARZILAI: Thank you so much! McCASKILL: Thanks! Thank you very much.
Thank you.
Terrific to meet you guys.
Thanks so much.
There's a ways to go before most Americans understand that this is maybe the most exciting scientific development in terms of the health care community that could happen in our lifetimes.
NARRATOR: Extraordinary progress has been made in the science of aging, but many older people still face difficult decisions about their health every day.
E.
KAMIN: At Martha's age, with Martha's other medical problems, if you allow modern cardiovascular surgeons to fix it, getting it fixed would reduce her two-year mortality somewhat.
M.
KAMIN: I've had the opportunity to observe other individuals here at Charter House having that surgery.
Some of them come out of it nicely.
But there's an awful lot of them that life changes drastically for them.
[bell rings.]
E.
KAMIN: So we're gonna decline the elective surgery on this critically narrowed aortic valve.
M.
KAMIN: Well, I think we've done all the investigation, you know, to help me support my thought.
I mean, I've thought of death on many occasions, and I, I might talk rather bravely of it now, and I hope that I'll be peaceful and accepting.
But I really do think that life is a pilgrimage.
And that I'm, I'm on my way.
And I'm on a way that I'm really looking forward to.
NARRATOR: Today Dr.
Barzilai and his colleagues will try to convince the FDA to consider their study.
In advance of their critical meeting, they gather to prepare.
BARZILAI: We are here representing the field of the science of aging, and we think that this is a historical day for us, because we are going to offer something that we believe is paradigm changing.
I really want to frame the discussion today as what would we need to show in a clinical trial that would allow the FDA to approve a new indication for metformin for delaying multiple morbidities related to aging.
Because we think metformin is the first one, but there are others that could be better than metformin, and we want to make sure that that's the template.
MICHAEL POLLAK: We have that hypothesis that metformin is one of those rare opportunities where it might act in a general fashion.
It's an attractive hypothesis, the trial is required to see if it's true.
NARRATOR: It started with a conceptual innovation, that aging can be modified.
Then years of work by a growing number of scientists in labs around the world and years of convincing people of their ideas.
Maybe this is what a breakthrough looks like.
If the FDA Accepts that aging can be treated, the scientiste believe it will forever transform health care and medicine.
OLSHANSKY: I don't think that there are too many interventions in history that would rival the type of intervention that we're talking about.
It would influence almost everyone.
NARRATOR: As a matter of policy, the FDA does not allow cameras into official proceedings, but they did agree to an interview immediately following their meeting.
ROBERT TEMPLE: We have lots of experience with claims to decrease the rate of heart attacks, to decrease the degree of dementia, drugs that prevent strokes, drugs that treat your diabetes.
We have lots of experience with all that.
But what's being sought and being talked about is a more broad claim to prevent a lot of the consequences of aging.
So the question for us is how do you show that? AUSTAD: We gauged their willingness to accept the general approach of targeting aging.
Something that they said right off the bat, we've never done anything like this before, and they were very receptive.
TEMPLE: Their hope is that a wide variety of age-related problems, you know, loss of muscle tone, dizziness, falling, dementia, loss of eyesight, all of those things, to do them all at once with a single treatment.
That might make a convincing case that you're doing something beyond just treating the disease.
That would, that would be something never done before.
AUSTAD: They didn't have any problem with the general approach, and I asked them specifically at the end, 'This is what I think I'm hearing, and you don't have any problems with the general approach.
' And they basically said yes.
So, I don't think we could have had a better outcome.
TEMPLE: If you really are doing something to alter aging, the population of interest is everybody.
It surely would be revolutionary if they can bring it off.
There's no doubt about it.
BARZILAI: We always thought that the promised land is not in our reach.
And I think that we are going to the promised land.
The study will happen.
The fact that the FDA is going to be part of it is really a major achievement and eventually will be the template and affect health span in the next decade.
E.
KAMIN: Your best smile, Martha, one, two, three.
That's almost perfect.
We're gonna take just another 25, Martha.
One, two, three.
DEMING: When I was a kid, I decided that I was gonna do two things in life.
One of which was to fly in some fashion, the other one was to cure aging.
OLSHANSKY: The long-term goal that all of us have is simple.
We want to extend the period of healthy life.
WOMAN: Celebrate your birthday all together! OLSHANSKY: We can see it.
It's like a window has been opened.
We know it's a desirable goal.
We have evidence that it, that it can be done.
Set it as a goal and pursue it, and pursue it aggressively.
One, two, three.
MELOV: When a breakthrough happens where we can improve the health span, improve the function of a human being, that is going to change everything.
LITHGOW: We're gonna have medical professionals trained who don't know anything about Alzheimer's, don't know anything about Parkinson's disease, very rarely encounter cancers.
And I think we'll just think of it as the new normal.
And I think it'll be a better place.
KENNEDY: I hope we look back on this era and say, wow, the medical community was on top of this and they developed interventions that kept everybody healthy longer, prevented these diseases, lowered health care costs, and kept the world economy growing.
E.
EMANUEL: Today the average life expectancy is about 79 years.
Would it be a much better life if we live to 84? Hard to convince me of that.
For me, it's the focus on how do I make the most of my life and the years I have.
Raise the family well.
Make sure I've contributed to my community.
I think it's absolutely pivotal to leading a good life.
BARZILAI: If we succeed, I think medicine will be different.
We won't have so many sick elderly.
And that will be good for them, and it will be good for health care.
It will be good for the economy, and it has only pluses if we can achieve that.
Will the circle DEMING: I think the thing that's driving most aging biologists is just this vision of a person who is 90 suffering a lot.
And this terrible last 20 years of life could actually be avoided.
The key motivator for everything that I do is this just gut feeling that it's wrong and terrible and that we have to do something about it.
In the sky In the sky
MAN: When the bloom is off the rose MAN: It's fix up, paint up, patch up.
You got to stay young.
MAN: It is a tonic, an elixir, to purge the body and lift the spirits.
WOMAN: Tell me, how great is the power of this liquid? MAN: For a long time people have been seeking the fountain of youth.
With the belief that there's some magical substance that will slow aging.
NEWSCASTER: Scientists say the fountain of youth could lie in MAN: Strawberries.
MAN: Red wine.
MAN: Omega-3 fatty acids.
MAN: Plain, old vitamin C.
OPIE: It's just another commercial.
AUNT BEE: I'll take two! MAN: The difference now is we have a really solid science which is pushing forward into the future, and it is uncovering mechanisms which modulate aging.
MAN: We know it's possible, at least in mice.
So it means it should be possible in humans if we put our minds to it.
MAN: If we can slow aging in humans just a little bit, the impact, it is monumental.
People can be older and feel young.
It takes you 70 years to become 50.
But enough advances have been made in aging science to lead us to believe it's plausible, it's possible, it's been done for other species, and there's every reason to believe it could be done in us.
WOMAN: We know that aging is modifiable.
MAN: The future is taking the biology that we've now developed and applying it to humans.
MAN: This would be the most important medical intervention in the modern era.
An ability to slow aging.
NARRATOR: In New York City in early 2015, a group of experts on the biology and demography of aging gather to discuss an ambitious new plan to change the way we think about aging and disease.
NIR BARZILAI: I'm going to ask you, how do we change the world? NARRATOR: Over the next several months, they will unveil a pioneering study designed to convince the world, and critically, the Food and Drug Administration, to recognize an entirely new category of drugs for the purpose of slowing aging in humans.
JAY OLSHANSKY: When you go to the FDA to seek approval, you're seeking approval for a treatment of a disease, right? What we're doing is we're seeking approval for a treatment of all diseases.
BARZILAI: This idea that we can delay aging is a new idea.
And the recognition that aging is part of every disease is not really well-established.
STEPHANIE LEDERMAN: When there's an article about we could cure cancer, nobody says, 'Oh, it's such hype.
' They believe in it, but as soon as you talk about aging, then it's snake oil or what are you trying to do, or there's too many old people.
Thousands of things come forth.
BARZILAI: We need to convince a lot of other people of what we're doing.
We need to convince the public.
LEDERMAN: Will it happen in our lifetime? BARZILAI: We need to convince the press.
OLSHANSKY: Come in, because there may be dangers.
BARZILAI: We need to convince the politicians.
JOAN MANNICK: You're setting the bar so high.
BARZILAI: We need to convince the FDA.
Because we're sure of the science.
We're sure of the promise, but the time is now.
NARRATOR: Time has flown for baby boomers like me.
In the next 15 years, the last of us will reach the age of 65.
Between now and 2050, the number of people over 65 in the United States is expected to almost double.
Worldwide, it will nearly triple.
Older people will make up an increasing share of the total population.
We can expect to see more of our parents and grandparents out of the workforce, battling cancer, heart disease, diabetes, frailty, and Alzheimer's, with dire consequences for our economies and health care systems.
OLSHANSKY: We need to demonstrate that this research is worth doing and that the consequences would be a public health revolution.
MANNICK: That's why we need you guys.
BARZILAI: That's why we need to do this study.
MANNICK: Right.
LEDERMAN: They have to see proof that this can be done.
And that's what we're trying to do, is give them that proof.
OLSHANSKY: What happens if we don't succeed? BARZILAI: We'll die trying! [laughter.]
NARRATOR: Why would they think they can modify the aging process? Only recently have mainstream scientists agreed that it might even be possible.
LAURA DEMING: I never went to school.
I taught myself everything from calculus to biology.
I knew that I wanted to be a scientist, like, from day one.
That was a given, it was just what field? And at first I thought, you know, cancer was the most important problem, and then I realized, no, aging is the most important problem.
We should go focus on that.
And then the rest of it was just kind of trying to figure out how to be a biologist.
And when I was 11, I emailed a woman called Cynthia Kenyon and asked if I could come see her lab.
CYNTHIA KENYON: Dear Professor Kenyon, I am 11 years old.
DEMING: And ever since I was six, have developed an acute interest in the study of the extension of human life.
KENYON: And I was wondering if I could meet you to ask some questions about a career in biology.
DEMING: Of course what I really meant was I want to come work in your lab, but that was the best way to say it.
I imagined Cynthia's life was this kind of whirlwind of being a superhero.
Staying up late at night and sleeping in the lab and making discoveries, like, having eureka moments continuously, and loving life.
Meeting her for the first time, it was like meeting the person that I always wanted to be.
KENYON: This is this one that you saw on the Internet.
DEMING: Oh, that's amazing.
KENYON: I'm sure it's the one.
This is about the time that we were making our discoveries.
None of these people worked on aging, though.
They were all working on other projects.
And it was a long time till anyone would work on aging, because people were afraid of it.
People, for years, had been comparing old and young.
Then they would have theories for why aging took place.
But there was no mechanism, like this dial, that you could turn up or down and change the rate of aging.
So I was studying worms, and my plan was to just change genes at random and look for worm mutants that live longer.
We taped worms for five minutes every day for their whole lives.
I had these little petri dishes.
One had normal worms, old, and the other had the mutant ones, moving around.
And I thought, I want to be those worms.
DEMING: Cynthia's fundamental finding was that you could change a single gene in a worm and have that worm live twice as long as normal.
GORDON LITHGOW: That was an incredible moment.
And frankly, people didn't believe it.
You could change a single gene and see a 70%, 75% increase in longevity.
SIMON MELOV: And that started to propel this idea that maybe aging was just like any other biological phenomenon.
Maybe you could manipulate it through the power of genetics.
KENYON: And right about 1998 or so several labs working on fruit flies showed that if you change the same gene, they live longer.
LITHGOW: Then people started doing this with chemical compounds, showing similar effects.
MELOV: That movement slowly started to expand and proliferate into other disciplines.
KENYON: Several labs found that making similar gene changes could also extend the lifespan of mice.
LITHGOW: We know of hundreds of genes now that when altered, changed the lifespan.
So aging itself is modifiable.
The question now is, is it modifiable in us? NARRATOR: In 1900, average lifespan was about 50 years.
A child born today can expect to live to be almost 80.
Astonishing progress in science and medicine have given us considerably longer lives, but as more of us live to an old age, we are facing protracted periods of sickness and decline.
BARZILAI: If we achieve long life, and the price is that we are sick for more of it, we're not really doing very well.
So how can we achieve longer, but healthier life? Centenarians are a clue.
They're a clue for us of how to live healthier as we live longer.
NARRATOR: What if we were vibrant up until the very end, and then passed away after a short period of sickness? Nir Barzilai has been studying a group of exceptionally healthy 100-year-olds or centenarians.
BARZILAI: Hi, Milton.
MILTON NUSSDORF: You're like the mailman, you're on the button.
BARZILAI: So nice meeting you.
How are you? NARRATOR: He believes they're a model for how we can all age.
NUSSDORF: Come on in, fellas.
RITA GOLOMB: Hello.
BARZILAI: Hello! GOLOMB: Oh, hi! How are, how are you? BARZILAI: How are you? One of the interesting thing with those centenarians is to see how they interact with the environment.
And we thought, hey, maybe they do all the right things.
Do you eat something special? Do you GOLOMB: No, I try to keep a healthy diet.
BARZILAI: What about exercise? NUSSDORF: Exercise.
I walk about a quarter of a mile for breakfast.
GOLOMB: I swam every day.
NUSSDORF: So my body has always been, uh, activated.
BARZILAI: And when you look at the population, you find almost the opposite.
NUSSDORF: I go every, just about every afternoon to Dunkin' Donut.
And I have coffee there and a Boston Kreme, that sort of thing.
BARZILAI: Your eating habits are not necessarily healthy, right? NUSSDORF: That's true.
GOLOMB: I smoked for 50, so, 50 years.
BARZILAI: 50% of them are obese.
50% of them do not exercise.
60% of the men and 30% of the women are smoking.
So it's in spite of all that, that they have some protection that allows them easily to get to age 100.
What we do find that they have is genes that are protecting them against anything that's thrown their way.
Those are individual cells that have mutations we think are associated with longevity.
And we follow what those mutations are doing to the cell.
What happens when you put the cells into a hostile environment? The reason we're looking for those mutations is that we think that those mutations will slow the rate of aging.
NARRATOR: Barzilai believes, from a biological perspective, his centenarians are aging slower than the rest of us.
His plan is to prove that medications can make us all age more like them.
BARZILAI: When you do genetic study, the public thinks that we need genetic treatment for those diseases, but no, we cannot change your genes, so that you become 100 years old.
But we can design medications based on our knowledge that will interfere with this pathway, and interact, intervene and delay the effects of aging.
MARTHA KAMIN: Well, I remember I gave him his first camera.
ED KAMIN: It's not easy to be the wife of a persistent photographer.
Martha studying in college.
M.
KAMIN: Ed asked me if I would like to go down to the cafeteria.
That was our first date.
E.
KAMIN: That was taken by a relative at our wedding.
Martha's so anxious to get married on this day.
M.
KAMIN: Well, I had been waiting seven years.
[laughs.]
Oh, that's our son, Thomas, who was 4'13 when he came home from the hospital.
He was smaller than Dad's shoe.
Oh, this one is a little bit more typical.
[laughs.]
E.
KAMIN: Ahh, I don't know if it's typical, but there's seven children, and everybody's happy, everybody's smiling.
This is back in the mid '70s when Martha was climbing mountains before her heart disease began to catch up with her.
M.
KAMIN: I liked the fact that I got up there before you and before Tom and before Mark.
[laughs.]
E.
KAMIN: This picture was taken with a self-timer.
It's a good photograph.
Two old people, hand in hand, going down into the uncertain future into the dark woods.
But it's as artificial as can be because of the self-timer, tripod, I ran, got into position.
M.
KAMIN: Turned right around.
E.
KAMIN: Turned around and got the dickens out of there.
[laughs.]
NARRATOR: Dr.
Ed Kamin and his wife Martha live at the world famous Mayo Clinic's retirement community after seven children and a long career in medicine.
M.
KAMIN: Well, I think that every day is a gift, and I hope that I can have that same attitude when perhaps I'm not as fortunate as I am right now.
You know, but E.
KAMIN: You mean when your batteries run down in your skull? [laughs.]
[knock knock.]
SARAH CRANE: Hello! I am Dr.
Crane, Sarah Crane.
E.
KAMIN: Ed Kamin.
Used to be a doctor.
JIM KIRKLAND: Jim Kirkland.
How do you do, sir? E.
KAMIN: Hi.
CRANE: Geriatrics is extremely complex medicine in the sense of multiple diseases going at the same time.
What are the issues that you're dealing with from a health standpoint right now? M.
KAMIN: I have osteoporosis.
E.
KAMIN: Five hip surgeries.
Breast cancer.
M.
KAMIN: Aortic stenosis.
CRANE: Okay.
E.
KAMIN: Martha now is the proud owner of four stents in her coronary arteries.
I think the record is 73, Martha, so you've got a long way to go.
M.
KAMIN: Oh, good.
KIRKLAND: In medicine, we've come up to the point where we're making incremental gains.
If we cured cancer, if we cured Alzheimer's disease, if we cured heart attacks and strokes, we would still die of something else a few months or a couple of years later.
That's because fundamental aging processes predispose to these diseases and conditions.
CRANE: We're beginning to hit a ceiling of healthy aging, because we're really great at treating diseases.
We are not so good at treating aging.
The burden of illness and of debility within the community is going up.
M.
KAMIN: Walking from here over to the clinic is a little bit beyond me.
CRANE: Mm-hmm.
E.
KAMIN: Primarily for the orthopedic problems.
But the heart problems are there, too.
CRANE: Most people don't really want to spend their last five years visiting us every day, or going to cardiologists every day or being in the hospitals or those types of things.
That's not quality of life at this point, so to be maintaining your functional status for as long as possible is the ideal.
You get to enjoy your grandkids, travel around the world, do all the things you want to do.
And then one day you don't wake up.
NARRATOR: The goal is to make us less sick at the end of our lives.
Researchers at the Buck Institute in Northern California are looking for ways to prevent the many diseases associated with aging by slowing the aging process itself.
To discover drugs that will one day increase health in human beings, researchers start much lower on the evolutionary ladder with single-cell organisms.
BRIAN KENNEDY: The nice thing about yeast is that we can keep billions of them in the laboratory very easily.
If we're testing drugs, we can look at 20 or 30 drugs in a single week looking at yeast cells.
It's so fast.
NARRATOR: If a chemical compound works in yeast, they test it in more complex organisms.
Conditions seen in aging animals like worms have surprising similarities to serious diseases seen in aging humans.
LITHGOW: We've shown recently that during normal aging in worms, there is an accumulation of insoluble proteins, and we believe this material is toxic.
And lo and behold, that's exactly what many people in the Alzheimer's field have been thinking about for years.
The sticky stuff that we find in the brains of Alzheimer's patients.
The compounds that extend lifespan also reduce Alzheimer's disease proteins, Parkinson's disease proteins.
If you target an aging process and you slow down aging, then you slow down all the diseases in the pathology of aging as well.
MELOV: Once we have identified from potentially screening thousands of compounds, a hit, we consider whether or not to apply that in a laboratory mouse.
NARRATOR: The dreaded fall, the broken hip, fragile bones are feared by the elderly.
MELOV: You get a fracture, you go to hospital.
You're more likely to go in a downward spiral and not come out.
NARRATOR: Using computerized tomography, high resolution images of aging mice help identify compounds that could slow the degeneration of bones.
To develop new drug therapies for aging, we need a more complete picture of how those therapies affect cells.
At GE's Global Research Center, Dr.
Fiona Ginty has found a way to image human tissue in unprecedented detail.
FIONA GINTY: We've developed a new technology here at the research center that allows us to see multiple proteins within a tissue sample.
NARRATOR: Using dyes to highlight individual proteins, she can create a sophisticated map of the quantity and location of those proteins in a tissue sample.
GINTY: By doing an analysis of all the proteins, you discover how those cells are responding to therapies.
Ultimately, those are the complete picture of biology and how in turn longevity is influenced.
NARRATOR: At the Mayo Clinic, Dr.
Jim Kirkland and his team are focused on taming another mechanism of aging, senescent cells.
KIRKLAND: Senescence is a process where cells that normally divide lose their ability to divide.
They become resistant to dying, and they produce things that kill the cells around them.
We discovered drugs that we call senolytic drugs.
We found they cleared senescent cells in mice.
This is seven days after the last dose of the drugs.
By targeting senescent cells, we can delay or even prevent or alleviate age-related diseases.
NARRATOR: To measure the effect of getting rid of these senescent cells, Dr.
Kirkland sends his mice to the gym.
KIRKLAND: One of the things that decreases with aging is their endurance on a treadmill.
So we gave senolytic drugs to very old mice.
We gave them to mice that had had difficulty with their walking.
We found that up to seven months after just one dose of these drugs by mouth, they were walking as well as healthy mice.
NARRATOR: In an increasing number of labs around the world, scientists have shown that they can improve health and longevity with drugs that treat fundamental aging processes.
KIRKLAND: We can do a lot of this now in mice.
The push now is to test can we really translate these things into people? LITHGOW: We're beginning to look at normal aging processes and one by one tick them off and say, 'Ah, that's why this disease is associated with aging.
' MELOV: Aging is a tractable phenomenon.
It's something you can study.
It's something you can manipulate.
That's a very exciting time to be in human history.
You're talking about developing a therapy for a biological phenomenon which is universal and gives rise to all of these diseases with time.
And if you've got a therapy for this thing, these diseases just go away.
DEMING: I love science.
That's where I come from is from just thinking that science is the place that you should start.
But I think that the gap is that everyone else who is like me, who loves science, just stays in science.
When I was 14, I applied to MIT.
And so I was there for two years, but then right around the end of my sophomore year had this big moment.
I'd been working on aging science now for, like, six years and just, you know, nothing had kind of happened, and it was all still in the research stage, and there were literally zero drugs out there.
So I dropped out of MIT, came to Silicon Valley and started a venture capital fund.
And that specific goal of having a drug in people in 10 years, I think would be impossible to accomplish by just staying in academia.
And so the reason that I left was to just work on that and making that process happen.
I'm on my way to see Nir Barzilai, who is at the Albert Einstein College of Medicine, because I've heard that he and some of his colleagues are looking into ways to get the FDA to take aging more seriously as an indication.
NARRATOR: It's not possible to create an FDA-approved drug for aging because they simply don't recognize that such a treatment exists.
BARZILAI: There are several drugs that are in human use, that we have been testing, and we show that they slow aging in a variety of animal models.
NARRATOR: Metformin, a widely used generic diabetes drug, has been shown to delay aging in animals.
Early observational data suggest it may do the same in people.
BARZILAI: Why metformin? Because we have great preliminary data.
There was a study from the UK.
It took people with early diabetes, just diagnosed, and treated them either with metformin or several other drugs.
This is what made me so excited.
They took 78,000 people that were just put on metformin, and they matched them with 78,000 people that don't have diabetes.
All the people with metformin have diabetes.
DEMING: Yup.
BARZILAI: And the cool thing is that people on metformin that had diabetes, they were more obese, they had more diseases to start with, had 17% less mortality than the controls without diabetes and without diseases.
DEMING: So you must have just looked at that and said, 'We have to do this.
' BARZILAI: Right.
The summary of what I'm telling you is that we're going to take people between 70 and 80 years old, and we're going to monitor those four things where we have preliminary data.
Prevention of diabetes, prevention of MCI and Alzheimer's, prevention of cancer, prevention of dementia, and prevention of mortality.
NARRATOR: Dr.
Barzilai and his colleagues say that metformin may not be the ultimate drug, but the important thing is to get the FDA to accept the idea of a drug that slows aging.
BARZILAI: So we take metformin, really as a tool, because metformin is generic, is cheap, is safe.
People have been using it for 60 years.
And we want to treat a bunch of people and show the FDA that we're going to slow the rate of aging.
DEMING: When I first came out to Silicon Valley, I was young and naive and I thought, oh, um, you know, if we can just show people that the science is good, and that the scientists believe this is worth doing, that's what will make them excited about aging.
And then I talked to this venture capitalist, one of the first people that I talked to who said, 'The only that I care about is what the FDA thinks.
' And that's it.
People in biotech will just sit in a room and be like, 'Okay, what should we fund?' And, and should we fund diabetes or cancer or, you know, and all these list of medications that they can put, you know, billions of capital into.
And aging is never on that list, and it's never on the list because the FDA does not see aging as a thing for which you can do a clinical trial.
BARZILAI: If we succeed with the FDA, we're going to change health care as we know it, because all those biotechs, pharmaceuticals will go in and think that way, and they'll develop drugs that will get better and better as they've done for other diseases.
DEMING: If you were to successfully run this trial, that would change everything about what I do, what most people in the venture capital field, I mean, that would be incredible for the field as a whole.
NARRATOR: Why do we think about treating sickness in terms of individual diseases? Most of the gains in life expectancy in the 20th century were due to our success in treating infectious diseases like pneumonia, flu, and tuberculosis.
Demographer Jay Olshansky believes that we are the victims of this success.
OLSHANSKY: The difficulty is a conceptual way of thinking, which is one disease at a time as they crop up.
It's the old infectious disease model applied to chronic fatal diseases.
The infectious disease model was what existed prior to 1950.
As soon as you experience an infectious disease, you go to your doctor, your doctor treats you, pushes you back out the door.
Get the next infectious disease, you go back to your doctor.
The doctor treats you, pushes you out the door.
So what are we doing? We're applying this infectious disease model to chronic fatal diseases.
Heart disease, cancer, stroke, and Alzheimer's.
We've built all of these institutes, the FDA and others, around the idea that somehow all of these diseases are independent of each other.
The cure for cancer would yield about a three-and-a-half-year increase in life expectancy.
But if you slow aging, just a little bit, you influence all of the fatal and disabling diseases at once.
So the impact is far greater.
They're not used to attacking multiple diseases simultaneously.
So somehow we have to convince the FDA and others involved that if we, if we go after the underlying risk factor for all of the diseases, we'll call that aging, we can influence all diseases at once.
That's what we're trying to achieve.
NEWSCASTER: Now to Dr.
Ezekiel Emanuel, who is NEWSCASTER: A trained oncologist, Dr.
Emanuel is Chair of the Department of Medical Ethics and Health Policy.
RACHEL MADDOW: He's a former special health advisor to the White House Office of Management NEWSCASTER: Dr.
Ezekiel Emanuel argues that the quality of human life begins to drop off by age 75.
He says that he will opt out of medical treatments and let nature take its course.
EZEKIEL EMANUEL: I think the people who are doing this aging research, for a lot of them, it's a puzzle.
They're in the puzzle.
They're trying to figure out the puzzle.
You know, for the rest of us, who are sort of watching it and want to consume it, we have this sort of techno-utopianism, we believe it'll be better in the future, we're gonna somehow fight death, we're gonna live totally healthy, and then we're gonna fall off at the end of a cliff.
That's not the way the world works.
So at 75, I'm going to stop doing medical treatments where the purpose of the medical treatment is to extend my life.
I'm not going to spend my time going from doctor to doctor.
And I think it's going to make my end of life more focused on the living than trying to do everything to get a few more weeks or months out of it.
I remember my dad as this bundle of energy and enthusiasm, and he had a tremendous drive and zest for life.
E.
EMANUEL: He was 74 years old, he had a heart attack.
And I think everyone will say since that time, he's not been the same.
E.
EMANUEL: When did you start that different life? After your heart attack.
B.
EMANUEL: Yeah.
E.
EMANUEL: It should have been all finished at 75.
E.
EMANUEL: We all end up dying.
And we need to confront that fact.
Why are you living? What makes your life meaningful? And how does that relate to living as long as possible? I don't think a meaningful life is about stacking up more years.
E.
EMANUEL: What else? You talk on the phone.
You harass your kids on the phone.
B.
EMANUEL: No.
E.
EMANUEL: Maybe it's born out of the fact that I'm an oncologist and we've been promising a cure to cancer since 1972.
It's now more than 40 years, and we still don't have that pill for cancer, maybe we're gonna be faster in that pill for, you know, no morbidity in our life.
Somehow, I'm a little skeptical about it.
And you have to, I think, plan your life on a reasonable basis.
And today, the reasonable basis is we're not gonna have that pill.
If that pill comes along and you get 10 extra years, great.
But I wouldn't bet your last nickel, and the most important thing, I wouldn't bet your own life, that that pill's gonna be there for you.
I was taking my blood pressure that my pulse rate was about 108.
And he said, 'Heavens to Betsy, how long has that been going on?' E.
KAMIN: Martha was having a heart attack as she was trying to get over the flu.
NARRATOR: In the wake of her heart attack, Martha, at the age of 90, must consider whether to have major surgery.
The decision is complicated by her chronic conditions.
E.
KAMIN: Martha has a severely narrowed aortic valve, and that's a major risk to Martha's health.
It's at the point where it's called critical.
A 50% mortality predicted in two years.
THOMAS JAEGER: I'd say a lot of people die of heart failure, related to aortic stenosis.
And that's not an easy road.
We're very good at treating symptoms.
And yet eventually your quality of life is kind of pulled out from under you.
PAUL McKIE: It's nice to meet you.
M.
KAMIN: Yes, same here.
McKIE: How are you doing? M.
KAMIN: Okay, I'm good.
I think I'm doing well.
McKIE: Great! Great.
When a person has a severely blocked valve, we think about opening up the valve or replacing the valve.
M.
KAMIN: Right.
McKIE: Any questions for me or concerns? E.
KAMIN: The frailty and the length of the convalescence, at age 90, that's gonna be a long convalescence.
M.
KAMIN: And the other thing is none of us like to lose our independence.
McKIE: Okay.
M.
KAMIN: I hate to think of him having to wait on me hand and foot.
[laughs.]
JAEGER: We can't kick this can down the road for a year, for instance.
If she waits a year or longer, then she'll probably have made a decision by default to say I'm just gonna let this take its course.
This is the best images of Martha's valve.
Those cusps of that valve should be opening completely.
CRANE: What we're seeing right now is something different.
The heart is stiff.
It's not that it's weak, it's just hardened and stiffened, and we have no medications for that.
I can't fix it.
I can't prevent it.
I can't keep it from getting worse.
It's a classic example of something that comes with aging that I can't fix.
E.
KAMIN: In my years of practice, I never found a patient who was feeling well, had accepted the infirmities of age, who said to me, 'Enough, I want to quit.
' Because it's wired into us that we want to continue living.
MAN: What if I told you there really is a fountain of youth? Would you believe me? MAN: Sign me up! NEWSCASTER: You want to get an edge on turning back the clock with just a few pills? Who doesn't? NEWSCASTER: Imagine this, you can live a healthy, vital, energetic life well past the age of 100.
NEWSCASTER: With just a few pills.
NEWSCASTER: It is possible NEWSCASTER: Remain.
NEWSCASTER: Younger.
NEWSCASTER: Vital.
NEWSCASTER: Vigorous.
NEWSCASTER: Planet Earth is a crowded place.
MAN: Trajectory is WOMAN: Six billion to seven billion.
MAN: People alive today may live a thousand years or more.
MELOV: There is this noise constantly, which is not surprising when you think about the subject matter.
The subject matter is our own mortality.
For thousands of years, we have had people prescribing cures for our own mortality.
NEWSCASTER: Some doctors prescribe human growth hormones.
MAN: Antioxidants.
BARZILAI: This is marketing, and people are reading that.
And people are concerned with their health and they're trying it.
NEWSCASTER: America's population is aging.
MAN: Very crowded.
NEWSCASTER: Humans are overpopulating the world.
NEWSCASTER: We're gonna have more people over the age of 60 than under the age of 15.
KENNEDY: The world is rapidly getting older.
There are not gonna be enough people working to pay for all the older people.
NEWSCASTER: It's very, very serious for the planet.
NEWSCASTER: There's a finite amount of resources.
NEWSCASTER: That means confronting a growing health crisis.
NEWSCASTER: In a finite world, you can't grow forever.
KIRKLAND: The bulk of morbidity, mortality, distress in the population, health costs, are related to these age-related chronic diseases that we're just seeing more and more of.
MELOV: But if we can really robustly develop therapeutics, which improve function with age KENNEDY: Then that grandparent is not being taken care of, but instead of that they're taking care of your kids.
They're contributing.
MELOV: People may work longer, productivity will be better.
NEWSCASTER: So you think there is someone alive today who could live thousands of years? OLSHANSKY: The immortalists are the ones who believe that we're gonna have radical increases in life expectancy up to 1,000 years, 5,000 years.
MAN: Exactly, I don't think there's any limit.
That there is nothing that would stop people intrinsically from living thousands of years.
KENYON: It's not really what the field is about right now.
It's so exciting we have things that slow down aging and affect diseases.
So now, let's get more of them, let's learn more about aging, and let's see what we can do for people right now.
OLSHANSKY: We have to constantly battle with this line of reasoning.
BARZILAI: How can we be heard when there is so much noise like that around us? If they can win support from the highest reaches of government, scientists believe they can change our nation's outlook on aging.
They meet with the ranking member of the Senate Aging Committee to make their case.
BARZILAI: So nice of you to meet with us.
CLAIRE McCASKILL: Of course.
BARZILAI: What people don't realize is we have found a way to intervene with aging, and these concepts have been proven in animals and is now going to be tested in humans.
The major risk for any one of the diseases is aging.
McCASKILL: Instead of thinking of it as an individual disease, thinking about it, okay, as we get older, this is what our bodies do, and we address that issue instead of, I've got to worry about diabetes, or I got to worry about a stroke, or I've got to worry about Alzheimer's? STEVEN AUSTAD: Yeah, what we've discovered is that basically, if we learn how to treat those underlying causes, we can delay all these diseases that kill and debilitate people as a group.
McCASKILL: People don't realize that just reducing adult onset of diabetes by a reasonable, modest percentage is enough to get us out of debt.
So I can imagine if we can do this across the board, just delaying slightly, and of course the train wreck that's coming, in all of our government programs is in fact the demographic bubble.
If we can get a handle on slowing the aging process, if we can actually do that, we are talking about a huge economic boon to this country.
OLSHANSKY: Every major public health advance in the 20th century had a champion.
Somebody who stood up and said I want this to happen, I'm gonna make it happen.
And we're hoping that sometime before the president leaves office, he raises this issue once again, considers it a global challenge.
McCASKILL: Well, I'll be glad to tell him.
OLSHANSKY: We would be delighted.
AUSTAD: We would love that.
McCASKILL: Yeah.
I will be glad to tell him.
OLSHANSKY: There's a lot of excitement in the field now, and we feel traction.
We can feel it.
We can sense that people are coming on board.
BARZILAI: Thank you so much! McCASKILL: Thanks! Thank you very much.
Thank you.
Terrific to meet you guys.
Thanks so much.
There's a ways to go before most Americans understand that this is maybe the most exciting scientific development in terms of the health care community that could happen in our lifetimes.
NARRATOR: Extraordinary progress has been made in the science of aging, but many older people still face difficult decisions about their health every day.
E.
KAMIN: At Martha's age, with Martha's other medical problems, if you allow modern cardiovascular surgeons to fix it, getting it fixed would reduce her two-year mortality somewhat.
M.
KAMIN: I've had the opportunity to observe other individuals here at Charter House having that surgery.
Some of them come out of it nicely.
But there's an awful lot of them that life changes drastically for them.
[bell rings.]
E.
KAMIN: So we're gonna decline the elective surgery on this critically narrowed aortic valve.
M.
KAMIN: Well, I think we've done all the investigation, you know, to help me support my thought.
I mean, I've thought of death on many occasions, and I, I might talk rather bravely of it now, and I hope that I'll be peaceful and accepting.
But I really do think that life is a pilgrimage.
And that I'm, I'm on my way.
And I'm on a way that I'm really looking forward to.
NARRATOR: Today Dr.
Barzilai and his colleagues will try to convince the FDA to consider their study.
In advance of their critical meeting, they gather to prepare.
BARZILAI: We are here representing the field of the science of aging, and we think that this is a historical day for us, because we are going to offer something that we believe is paradigm changing.
I really want to frame the discussion today as what would we need to show in a clinical trial that would allow the FDA to approve a new indication for metformin for delaying multiple morbidities related to aging.
Because we think metformin is the first one, but there are others that could be better than metformin, and we want to make sure that that's the template.
MICHAEL POLLAK: We have that hypothesis that metformin is one of those rare opportunities where it might act in a general fashion.
It's an attractive hypothesis, the trial is required to see if it's true.
NARRATOR: It started with a conceptual innovation, that aging can be modified.
Then years of work by a growing number of scientists in labs around the world and years of convincing people of their ideas.
Maybe this is what a breakthrough looks like.
If the FDA Accepts that aging can be treated, the scientiste believe it will forever transform health care and medicine.
OLSHANSKY: I don't think that there are too many interventions in history that would rival the type of intervention that we're talking about.
It would influence almost everyone.
NARRATOR: As a matter of policy, the FDA does not allow cameras into official proceedings, but they did agree to an interview immediately following their meeting.
ROBERT TEMPLE: We have lots of experience with claims to decrease the rate of heart attacks, to decrease the degree of dementia, drugs that prevent strokes, drugs that treat your diabetes.
We have lots of experience with all that.
But what's being sought and being talked about is a more broad claim to prevent a lot of the consequences of aging.
So the question for us is how do you show that? AUSTAD: We gauged their willingness to accept the general approach of targeting aging.
Something that they said right off the bat, we've never done anything like this before, and they were very receptive.
TEMPLE: Their hope is that a wide variety of age-related problems, you know, loss of muscle tone, dizziness, falling, dementia, loss of eyesight, all of those things, to do them all at once with a single treatment.
That might make a convincing case that you're doing something beyond just treating the disease.
That would, that would be something never done before.
AUSTAD: They didn't have any problem with the general approach, and I asked them specifically at the end, 'This is what I think I'm hearing, and you don't have any problems with the general approach.
' And they basically said yes.
So, I don't think we could have had a better outcome.
TEMPLE: If you really are doing something to alter aging, the population of interest is everybody.
It surely would be revolutionary if they can bring it off.
There's no doubt about it.
BARZILAI: We always thought that the promised land is not in our reach.
And I think that we are going to the promised land.
The study will happen.
The fact that the FDA is going to be part of it is really a major achievement and eventually will be the template and affect health span in the next decade.
E.
KAMIN: Your best smile, Martha, one, two, three.
That's almost perfect.
We're gonna take just another 25, Martha.
One, two, three.
DEMING: When I was a kid, I decided that I was gonna do two things in life.
One of which was to fly in some fashion, the other one was to cure aging.
OLSHANSKY: The long-term goal that all of us have is simple.
We want to extend the period of healthy life.
WOMAN: Celebrate your birthday all together! OLSHANSKY: We can see it.
It's like a window has been opened.
We know it's a desirable goal.
We have evidence that it, that it can be done.
Set it as a goal and pursue it, and pursue it aggressively.
One, two, three.
MELOV: When a breakthrough happens where we can improve the health span, improve the function of a human being, that is going to change everything.
LITHGOW: We're gonna have medical professionals trained who don't know anything about Alzheimer's, don't know anything about Parkinson's disease, very rarely encounter cancers.
And I think we'll just think of it as the new normal.
And I think it'll be a better place.
KENNEDY: I hope we look back on this era and say, wow, the medical community was on top of this and they developed interventions that kept everybody healthy longer, prevented these diseases, lowered health care costs, and kept the world economy growing.
E.
EMANUEL: Today the average life expectancy is about 79 years.
Would it be a much better life if we live to 84? Hard to convince me of that.
For me, it's the focus on how do I make the most of my life and the years I have.
Raise the family well.
Make sure I've contributed to my community.
I think it's absolutely pivotal to leading a good life.
BARZILAI: If we succeed, I think medicine will be different.
We won't have so many sick elderly.
And that will be good for them, and it will be good for health care.
It will be good for the economy, and it has only pluses if we can achieve that.
Will the circle DEMING: I think the thing that's driving most aging biologists is just this vision of a person who is 90 suffering a lot.
And this terrible last 20 years of life could actually be avoided.
The key motivator for everything that I do is this just gut feeling that it's wrong and terrible and that we have to do something about it.
In the sky In the sky