- SHOW 1003
Eat Less - Live Longer
Clock of Life
Wisdom of the Worms
How to Make a Nose
Use It or Lose It
ALAN ALDA: This laboratory mouse has lived much longer than normal,
and it won't be long before humans can do the same. On this
edition of Scientific American Frontiers, science begins to
explore how we get old, and how we can avoid it.
ALAN ALDA: (Narration): We'll see how we could keep our bodies'
cells young forever. We'll discover how nature governs lifespans,
in worms and maybe people, too. We'll find out how to grow
spare parts for aging bodies. And we'll see how eating less
makes a long life, while doing more makes a happy one.
ALAN ALDA: I'm Alan Alda. Join me now for Never Say Die.
LESS - LIVE LONGER
ALAN ALDA: We may not like it, but this is where we all end up
after our allotted span. This is Albertine -- she lived 62
years; Sarah -- 45 years; Joseph -- 74 years. Many different
ages, but you won't find any past about 120, and the average
right now is in the seventies. But what if I told you, you
wouldn't have to check in here until you were 150 years old?
200? 250? Right now a lot of serious, smart Scientists are
beginning to say that's what's possible. They're starting
to understand the details of what makes us age, right down
to the level of our DNA. It's becoming realistic to think
about intervening in the aging process. Already there are
astonishing results with lab animals, with some living 4 times
as long as normal. In this program, we'll be meeting Scientists
whose work may help us live longer -- a lot longer. And we'll
also be asking what it would be like to live a lot longer
-- would life be worth living? But how do we get there? How
do we get to a longer life? This first way may surprise you...
ALAN ALDA: Hello… Hi Dr. Walford? Glad to meet you. How are you?
I brought my lunch.
WALFORD: Oh you did, great.
ALAN ALDA: (Narration): I've come to see Roy Walford, in Venice,
California. For 30 years, Dr. Walford has been studying the
relationship between food and long life.
WALFORD: I think it would be better if it were like whole
wheat bread. I would say that's two slices of white bread.
ALAN ALDA: Let's see what else I have. You probably don't like
this. Sometimes I like something crunchy while I have a sandwich.
WALFORD: Well pretzels are empty calories so, I don't like
ALAN ALDA: How about pickles?
WALFORD: OK. That's all right.
ALAN ALDA: Well this is all just for taste. How do you feel about
WALFORD: It doesn't add much in the way of calories unless
you use a huge amount.
ALAN ALDA: (Narration): For Walford, watching calories is only
one of the keys. He believes if you eat less, you'll live
longer -- so long as you make sure that what you do eat has
high nutritional value. I'm aiming to make a pretty lo-cal
lunch -- no more than 500 calories.
ALAN ALDA: You use a lot of calories getting the pickle jar open
WALFORD: Yes, that's the whole point. That's your exercise.
ALAN ALDA: This is about it. This is what I could…now, now, let's
see that wouldn't be enough though. I'd still be interested
in more. I'd probably eat five or six of these pretzels. I
would take the salt off the pretzels. I don't like to eat
a lot of salt. Then I would have probably, to make myself
feel better, I'd either have about four ounces frozen yogurt
or ah, if I was feeling really healthy, health minded, I'd
have an apple. Let's say an apple.
ALAN ALDA: I would give myself the benefit of the doubt.
ALAN ALDA: (Narration): Now let's see what kind of nutrition my
lo-cal lunch delivers.
WALFORD: Let's see, turkey breast-no skin, roasted is about
as close, and you didn't have half a breast but maybe a quarter
of a breast. You added a piece of tomato in that.
ALAN ALDA: Yeah, two little slices of tomato.
ALAN ALDA: (Narration): When you add it all up, I did fine on the
calories -- but that's about all.
WALFORD: What you had is deficient in A, B12, C, E, folic
acid and panithinic acid. Among minerals it is deficient in
calcium, copper, magnesium, manganese and zinc.
ALAN ALDA: And what's that big tall yellow one? What's that?
WALFORD: Well that means it has a great deal of sodium.
ALAN ALDA: Oh, I'm doing fine with the sodium. OK.
ROY WALFORD: And you have too much cholesterol
ALAN ALDA: Where'd I get that from? The turkey?
ROY WALFORD: From the turkey probably, yeah.
ALAN ALDA: (Narration): But here's what goes into Walford's lunch.
Every one of his 500 calories packs a high nutritional punch.
ALAN ALDA: How did you first get interested in this?
WALFORD: I got interested in this kind of nutrition because
it's been known since 1935 that if you keep animals on a very
low calorie diet but one that is not deficient in vitamins
and so forth, you extend their maximum lifespan and their
ALAN ALDA: (Narration): In the 1960's Walford, who's a
at UCLA medical school, set out to refine the low-calorie
studies. He confirmed that laboratory mice live up to twice
the normal age if calorie intake is reduced by up to half.
At the same time he detected intriguing signs of improved
health -- lower blood pressure, lower insulin and cholesterol;
and stronger immune systems. Then in 1991 Walford joined Biosphere
2 as the project doctor. He was part of the team which sealed
itself inside a 3-acre greenhouse. The aim was to be self-supporting
-- to subsist entirely on the miniature ecosystems growing
inside. Things didn't turn out as expected. Food production
was about 40% short, but for Walford it was a lucky accident.
Like it or not, the team found itself on a low-calorie, high-nutrition
diet. The team members went hungry. But in regular medical
exams, Walford discovered they were developing the same good
health patterns as the lab animals. Biosphere 2 confirmed
for Walford that a low-calorie, high nutrition diet is likely
to benefit humans, and he has been following it ever since.
It sounded pretty good to me. How do you get started?
WALFORD: What you wanna do is lower the calorie content so
that you lose weight gradually until you're 10-20% below your
set point - where your set point is defined as what you would
weight normally if you ate just kind of a normal diet.
ALAN ALDA: That sounds like, ah, a lot of weight loss. I mean I'd
be a bean pole without the beans, I think. I mean, that sounds
severe to me.
ALAN ALDA: (Narration): These lively rhesus monkeys are on
just such a severe regimen. I'm visiting Rick Weindruch at
the University of Wisconsin.
ALAN ALDA: Is this for my protection, or for the monkeys'?
RICK WEINDRUCH: I think its mutual for both, yes.
ALAN ALDA: Okay.
ALAN ALDA: (Narration): Weindruch has about 80 monkeys --
half on restricted calories, half normal. The study has been
running for a decade, and the animals are now 20 years old
-- middle age for rhesus monkeys -- so there won't be any
results on life span for a while.
ALAN ALDA: Which kind? What does he get?
This guy up above.
ALAN ALDA: (Narration): The restricted diet is exactly like
Walford's. In fact Rick Weindruch was his student at UCLA.
ALAN ALDA: Here you go, pal.
ALAN ALDA: (Narration): The monkeys' calories are reduced, but
their nutrition is excellent -- it's not in any way a starvation
diet. So within the next few years, as old age should be approaching,
the expectation is that the normally-fed group will begin
to lose its health, while the calorie-restricted group will
WEINDRUCH: We're starting to see signs of better health in
our restricted animals. It's going to really be, shall we
say, show time for these diets over the next five years.
ALAN ALDA: (Narration): Just like Walford's Biosphere team, the
monkeys get regular checkups, although they're sedated for
some procedures. This is a scan for bone mass, which tends
to become reduced with age. They also examine tiny samples
of muscle from the monkeys, looking for signs of cellular
damage which normally develops with age.
ALAN ALDA: Is this part of a cell?
RICK WEINDRUCH: This is a component of a cell and this is
the stuff that makes your muscles contract, basically.
ALAN ALDA: (Narration): This black dot in the muscle of a 4 year-old
monkey is damage caused by things called free radicals. Free
radicals could explain why eating less helps you stay healthier
and live longer. Nutrients from the food we eat get absorbed
by every cell of our body. These nutrients normally combine
with oxygen to make essential energy-storing chemicals. But
an unavoidable by-product is the production of free radicals
-- reactive oxygen compounds that damage whatever they hit.
The body makes chemicals, called anti-oxidants, which defend
against free radicals. But damage still accumulates over the
years, leading to all kinds of old-age diseases. The exciting
thing about Weindruch's study is that while 20-year-old monkeys
on normal diets show extensive free radical damage, calorie-restricted
monkeys -- who are the same age -- look like young kids.
ALAN ALDA: So this is a 17-year-old monkey with about the same
amount of free radical damage as, how old a monkey?
WEINDRUCH: A four-year-old.
ALAN ALDA: A 17-year-old as healthy as a 4-year-old.
ALAN ALDA: (Narration): Weindruch is also pursuing the free
radical theory with a large-scale mouse study.
ALAN ALDA: So one bunch is on a restricted diet and one... ah,
I'll tell you something that I see right away. These are really
active and these are just sitting around.
ALAN ALDA: (Narration): These are senior-citizen mice -- about
2 years old -- and they're on a normal diet. And these are
on calorie restriction. But Weindruch also has four other
groups being fed normal diets plus some special extra ingredients.
He's adding combinations of the anti-oxidant supplements,
like vitamins C, E, and beta-carotene, that so many of us
are taking now. The result so far -- not very encouraging.
Anti-oxidant dietary supplements are no substitute for calorie
restriction. They don't seem to affect life span one way or
RICK WEINDRUCH: The best survival at this point in time is
group 5 - our calorically restricted animals.
ALAN ALDA: Who aren't taking any supplements.
RICK WEINDRUCH: No, no their not.
ALAN ALDA: So, so far taking supplements, if you have a normal
diet, or any kind of diet, it doesn't make you live longer,
so far and you have a lot of time to go on this, but so far
you are living the longest…
RICK WEINDRUCH: …just plain old caloric restriction…
ALAN ALDA: …with high nutrition.
WEINDRUCH: Right, but again it's early so come back in a year,
ALAN ALDA: Yeah, yeah. Well meanwhile I'm taking the pills.
WEINDRUCH: Me too!
WALFORD: So Alan, I made 4 servings in the wooden bowl. This
is one serving and it's about 500, 550 calories.
ALAN ALDA: This is one serving? This is a lot of food!
ROY WALFORD: That would be one serving, yes.
ALAN ALDA: And this is equal to that sandwich I made? ROY
WALFORD: More or less. It's about equal in calorie content
to your turkey sandwich.
ALAN ALDA: It's very good. How old do you think you're going to
ROY WALFORD: Well, older than I would be. I've just been on
this diet for about 10 years or so, maybe a little more so,
I certainly didn't start when I was young. If my destiny on
a normal diet had been to live to be 90, then on the diet
I should add another 15 or 20 years. So that would put me
out to be 110, starting at 60.
ALAN ALDA: That's where it would put me, if I started around now.
110. See I always thought it'd be nice to live to 106. 110
is even better! This doesn't look so appetizing anymore. I
got plenty of crunch. I didn't need the pretzels. And this
wouldn't be bad for dessert, or am I denied dessert now?
WALFORD: No, that would be fine. Sure. An apple is good dessert.
ALAN ALDA: Your heart would sink if I took out the frozen yogurt
WALFORD: Well no, yours would.
CLOCK OF LIFE
ALAN ALDA: (Narration): From infancy to oblivion - it's the natural
and mysterious trajectory of our lives, and it's been that
way for the several 100,000 years we've been on this Earth.
Now suddenly we've begun to glimpse nature's machinery of
aging inside our cells. Throughout life, cells constantly
rejuvenate, through division, to keep our bodies healthy.
In the sixties it was discovered there's a lifetime limit
of about 50 divisions - and then cells die or start causing
trouble. But what if we could avoid this limit and let cells
divide forever? That's the extraordinary idea we'll explore
in this story. We start with a highly magnified picture of
human chromosomes -- the structures inside cells made of DNA.
On the ends of each chromosome are things called telomeres
-- highlighted here with a special dye. In the 1980s it was
discovered that telomeres get shorter every time a cell divides,
until the telomeres disappear almost entirely. I'm visiting
Geron Corporation, a small biotech company in Menlo Park,
California. Their chief Scientist, Cal Harley, is the man
who made this discovery about telomeres.
CAL HARLEY: The little plastic tip at the end of a shoe lace
is like the telomere. It functions to sort of protect the
end of the chromosome or in this case the end of the shoelace
from fraying and not being able to function.
ALAN ALDA: It seems to me that this thing that's acting like a
telomere would be useful for eliminating or holding off fraying.
For a long time it can get very, very, very short and it will
still do the job. Is the telomere like that?
CAL HARLEY: There is actually a critical point when the telomere
gets down to maybe less than 5% of its length at birth where
at that point there is a very strong signal that this cell
is in danger because there is some damaged DNA now being exposed.
ALAN ALDA: (Narration): Cal found that cells stop dividing when
telomeres run out. They're like the clock of life. Another
breakthrough came when Geron located the exact section of
DNA -- or the gene -- that governs the manufacture of telomeres
in cells. It's called the telomerase gene. At a Boston hospital,
Ronald Depinho is working with this gene to explore what happens
when telomeres finally run out.
DEPINHO: Let's take a look.
ALAN ALDA: (Narration): They've bred a special strain of mouse
which has no telomerase gene. Because mice normally have much
longer telomeres than people, it has taken a few generations
of the lab mice to get down to short telomeres. Now it's getting
DEPINHO: What we see are some obvious external manifestations
of short telomeres. We have a normal mouse here with a quite
normal looking coat color that has a nice black sheen to it.
And this is a mouse of equivalent age that has short telomeres.
And what we see are some obvious hair graying compared to
the normal coat color of this mouse here -- short telomeres,
normal telomeres. And still others have the additional problems
where they have accelerated hair lose.
ALAN ALDA: (Narration): Since hair never stops growing, hair cells
would be among the first whose telomere clock runs out. This
is some of the first solid evidence that telomeres can affect
at least the symptoms of aging. For the first time we can
shed some light on the tragic disease of progeria -- premature
aging. These are children, all under 12 years old, attending
an annual get-together of the 40 or so progeria kids in the
FOSSEL: Bonjour. Ca va?
ALAN ALDA: (Narration): Pediatrician Michael Fossel studies the
FOSSEL: These kids are born old. They have normal childhood
minds. They're bright. They're funny. They're typical of any
other child, but they also get angina, and they also get heart
attacks in the playground and they get arthritis. They have
old skin. They don't move well. They're shrimpy, you know.
But otherwise they're normal kids.
ALAN ALDA: (Narration): Progeria kids have the diseases of old
age, and we now know they have something else -- short telomeres.
Short telomeres mean cells can't divide and repair damage,
so disease starts. Now at least the door is open to a genetic
cure for these kids. You can get an idea how such a cure might
work back at Geron. Cal Harley showed me under the microscope
what human eye cells look like when they're young, healthy
and still able to divide.
FOSSEL: So Alan, here's an example of a young cell within
that population that is going through the process of division.
ALAN ALDA: (Narration): These are the cells dividing, using up
their telomeres. Now take a look at old cells, with no telomeres
left. They're literally bloated -- they've lost their youthful
lines. Abnormal cells like these cause the symptoms of old
age - cataracts, gray hair, wrinkled skin, arthritis, even
ALAN ALDA: What if you took telomerase and got it in there, could
you built up the ends, the tips of the shoe laces?
HARLEY: That's the million dollar question, is can we prevent
this process from happening or in part, reverse it?
ALAN ALDA: (Narration): Cal invited me to answer the million
dollar question for myself. Using the normal procedures of
the genetic engineering lab, I set about inserting the telomerase
gene into old human eye cells. This is an experiment first
done at Geron just 18 months earlier.
HARLEY: I'll just take that one for you
ALAN ALDA: See when I had chemistry, I didn't have a personal
coach like this. I would have done much better.
ALAN ALDA (Narration): The final step is to force the new genes
into the old cells with a Frankenstein-like electric shock.
And... bingo! It works. You get new, youthful cells.
ALAN ALDA: I'm kind of surprised at how vivid this is.
HARLEY: Yeah. The first time we saw it, we were very much
surprised. Even though this is what we were predicting and
hoping for, the impact of this is dramatic. Some of these
cells have been going now for 300 doublings, where the normal
cells age at 50.
ALAN ALDA: They are still ready for more.
HARLEY: Yeah. We sometimes call them immortal, but a more
accurate term would be indefinite division capacity.
ALAN ALDA: So if this were happening, let's say, in the skin on
HARLEY: What do you mean?
ALAN ALDA: You have to understand I'm an actor, during most of
the week. So if this is happening to the skin on my face,
the bags under my eyes would tend to go away by themselves,
ALAN ALDA: (Narration): Right now we don't know the answer
to my question. We can rejuvenate cells in a dish, but that's
not the same as repairing tissue damage on a large scale.
Here at UCLA, Rita Effros is working on one of the first applications
of large scale cell repair. The goal is to rejuvenate the
cells of the body's immune system, in the same way I did at
Geron with eye cells, by adding the telomerase gene. If old
folks had young and vigorous immune systems, they'd obviously
be able to fight off diseases more effectively.
EFFROS: What we're hoping to do is extend the life of elderly
people to the maximum limit that we now know is the human
limit, which is approximately 120 years. So we've hoping that
a person who is 100 or 105 would response better to an infection,
and therefore not die from that infection and continue living.
ALAN ALDA: (Narration): This work is now looking very promising.
For example, this is the response of a rejuvenated immune
system to a virus. The dark patches are dense swarms of immune
cells attacking the intruder. Compare that to the weak response
of a normal 80-year-old's immune system. Sometime in the next
few years, getting an immune system boost could become routine
for people over say 60. Many more people might conquer disease
and reach the 120-year limit. But can we go further?
ALAN ALDA: Will we be able to live 150 or 200 years? Is that possible?
HARLEY: There is no reason why genetically we can't have a
lifespan that could be 100, 200, 300 years. There is just
no theoretical reason that that is impossible.
ALAN ALDA: (Narration): To double or triple human lifespan is an
astonishing idea -- but don't dismiss it before you see our
OF THE WORMS
ALAN ALDA: (Narration): This is Cynthia Kenyon, a biologist at
the University of California, San Francisco.
ALAN ALDA: Is that it?
KENYON: There they are. There they are.
ALAN ALDA: Wow! Look at them move!
KENYON: Aren't they pretty?
ALAN ALDA: (Narration): Cynthia's crazy about nematodes -- tiny
worms, smaller than a grain of sand, that live in soil just
about everywhere. She's figuring out how nematodes age, and
she's pretty sure humans work the same way.
ALAN ALDA: Most of us would think, How is that possible? How could
the way a worm ages be anything like the way we age?
KENYON: They have all the same kinds of tissues in their bodies
that we have in our bodies. So for example, they have muscle
cells that let them move. They have a whole nervous system
that lets them go towards things they like, go away from things
they don't like. They have skin. They have an intestine that
looks a lot like our intestine. So at the level of individual
cells and tissues, these animals are very similar to us.
ALAN ALDA: (Narration): Normal nematode lifespan is just 2
CYNTHIA KENYON: This is a brand new adult worm. This will
be maybe a college graduate -- about that old.
ALAN ALDA: How old is he?
CYNTHIA KENYON: He's, in worm days, he's three days old and
he would be the equivalent of a twenty year old person. So
he's pretty frisky, moves around, has nice muscle tone. You
ALAN ALDA: The worm has nice muscle tone.
KENYON: He does! So he's moving through his food. This is
bacteria, that he's... a lawn of bacteria.
ALAN ALDA: That's a nice sinuous movement. What does an old guy
KENYON: Okay, now I'll get an old worm for you. Here's some
nice old worms. Here's a pair of them.
ALAN ALDA: Boy, they're just sitting out in the sun!
KENYON: Look at them. Look at them. There are two of them!
ALAN ALDA: They're on their lawn chairs.
KENYON: They are -- or maybe even in the nursing home. This
worm is still a little bit active but it's nothing like a
young worm. And look at its body, you see this big gap here
and these little pock marks? So it doesn't look young anymore.
It looks very old now. And actually what I think is really
interesting is that anyone in the world looking at these worms
can see that they look kind of old. So in other words, there
is something about the aging process that speaks to you, directly
from an animal of any type.
ALAN ALDA: (Narration): In a series of experiments that became
instant classics, Cynthia has made worms that live twice as
long as normal. First she gave normal worms a bath, in a rather
unpleasant chemical that causes random changes -- or mutations
-- in the genetic material inside the worms' cells. Next she
laboriously placed thousands of single worms onto their own
individual dishes. Now she could follow each worm over time,
generation after generation. Most worms died or lived shorter
because of their mutations. But in a few there was a single
change -- a change in one gene -- that led to longer life.
So now living in the incubator in Cynthia's lab is a strain
of mutant worm that lives 4 weeks, rather than 2. It's astonishing
to see a lively, young-looking worm that's the same age as
the old folks we'd seen earlier.
ALAN ALDA: Oh my God that really is...
KENYON: …this is a mutant worm. This is the exact same age.
ALAN ALDA: The same age!
KENYON: It's the same age -- I'm not kidding you. Look at
that. I mean it doesn't look like...
ALAN ALDA: I never looked at these worms before but this looks
the same. To my eye this looks the same as the three day old...
KENYON: Well it's a little different.
ALAN ALDA: How is it different? Show me how it's different.
KENYON: It's a little slower. It's a little bit bigger. But
you know, it is much younger in spirit than that one we just
saw. That's for sure. Isn't that amazing!
ALAN ALDA: It is amazing.
KENYON: I mean it's just unbelievable -- you change one gene
and essentially you cure this disease of aging, if you want
to put it that way.
ALAN ALDA: I'm taking this very personally here for a minute
ALAN ALDA: …well I'd like to live to about 106 -- at least that's
what I've always thought. But now I may switch. Maybe I'm
too modest - maybe I should go for 140 or so.
CYNTHIA KENYON: Why not?
ALAN ALDA: Yeah, well that is what I want to ask you, why not?
Because what I want to know is, this guy is 12 days old, he's
still thriving at 12 days -- 12 out of a 14 day usual life
span. He's going to go on another 2 weeks, right?
CYNTHIA KENYON: Yeah.
ALAN ALDA: Now, in those two weeks, how much of those two
weeks will be vigorous like this? When is he going to start
to act like a 100 year old, or a 110 year old person? What
do you observe?
KENYON: I would say that in about one more week this animal
will be still not looking as bad as the normal worms that
I just showed you, the normal 12 day old worms. But they will
be much slower. They'll be walking and not running.
ALAN ALDA (Narration): In other words, everything takes twice as
long -- youth, middle age and old age. This really could happen
with people some day, because Cynthia's rapidly figuring out
how the lifespan system works.
KENYON: Here it is.
ALAN ALDA: What is this, like a thousand times bigger than it ought
CYNTHIA KENYON: Even more than that I think because the normal
worm you can hardly see. So this is a zillion times larger.
ALAN ALDA: A zillion. Ah, I knew there was a number.
ALAN ALDA (Narration): In nematodes, lifespan is regulated
by hormone messengers that circulate in the body and land
on receptors -- like this blue mushroom.
KENYON: This red thing here is a cell. And the worm is actually
full of many cells and this is just one of them.
ALAN ALDA: Yeah.
KENYON: The receptor sits in the edge of the cell and its
job in the animal is to receive signals from the outside and
the signals that it receives are hormones. So this is a hormone…
ALAN ALDA: OK.
CYNTHIA KENYON We have lots of hormones in our bodies controlling
all aspects of our growth and our physiology. In the normal
worm, where the hormone is bound to the receptor, the consequence
is that the worms have a short life span.
ALAN ALDA (Narration): The mutation that extends life changes the
shape of the receptor so the hormone's blocked.
KENYON: And so the hormone can't fit in to its normal spot
-- see like that, it can't fit in there. And as the consequence,
the animal lives longer.
ALAN ALDA: Do you know why?
KENYON: We don't know all the details, but we do know that
one thing that is very important are these little orange balls
here. These, it turns out, we can call these fountain of youth
ALAN ALDA (Narration): With the receptor blocked, the cell makes
more youth chemical -- and that's the stuff the worm needs
to live. But in normal worms with working receptors, the fountain
of youth dries up.
ALAN ALDA: Why would nature arrange it that way if it's going to
lead to an early death? Is there some advantage to this nematode,
this individual nematode, dying in two weeks instead of what
you can arrange -- four weeks?
KENYON: We don't know. We don't know why the worm has its
own Grim Reaper inside of it. This is essentially the Grim
Reaper - it's cutting the life span short of the worm. We
don't know why that is. Evolution must have selected for it
and I don't really know why.
KENYON: So here goes, I'm going to start shooting the laser
at it. Now the way I do that is with the little foot pedal
ALAN ALDA (Narration): Cynthia has discovered a second lifespan
regulation system in nematodes, this time by disrupting cells
used in reproduction. She delicately knocks out the cells,
using a tiny laser.
KENYON: I think I've killed it now, yes. Here's the cell I've
been shooting at. When I started off it looked a lot like
this cell with a nice dish shaped center, but now you see
its gone, there's no round circle.
ALAN ALDA (Narration): Worms with reproductive cells destroyed
also double their lifespans -- and the mechanism is just like
the first system Cynthia discovered. In this case the worms
no longer make a second kind of messenger hormone, again resulting
in more youth chemical being made inside cells. So what happens
when one worm has both lifespan systems blocked?
KENYON: What we found is that it lives twice again as long.
ALAN ALDA: You're kidding!
KENYON: Yeah, it's a very amazing result. So it lives now,
instead of a human living like not 90 years but 180, its like
living 360 years. Do you see what I'm saying? You're doubling
the doubling of the life span.
ALAN ALDA (Narration): It's likely that all living things use these
same hormone messengers to regulate life span. The fascinating
thing is that the hormones are related to insulin, which is
made by the body when we eat food. So maybe that's why restricting
calorie intake lengthens life. Something like a long life
pill could be possible, once we fully understand these systems.
And some day we surely will, thanks to Cynthia
ALAN ALDA: Before you did this work did you have an age that
you thought you might live to, and now have you changed your
mind about what that age might be?
KENYON: Ah, yeah, I'm much more, er... Well I have to tell
you, I have a retirement account. So that means that at some
level I think I might have to retire at some point. So part
of me is living in the real world. On the other hand, I have
an imagination that I might not have to use it for a very
long time. It could get really big!
TO MAKE A NOSE
ALAN ALDA (Narration): It has never been hard to put together body
parts -- in the movies.
It's alive. It's alive. It's alive. It's alive. It's alive.
ALAN ALDA (Narration): But Hollywood better look out because MIT
scientists are getting in on the act.
ALAN ALDA: Does he have the nose?
BOB LANGER: Yeah, its coming.
ALAN ALDA: You got it? That's the nose?
It's right in the dish here.
ALAN ALDA (Narration): OK now, we are not, repeat not, on a movie
ALAN ALDA: Wait, what is this?
This is cartilage. It is a scaffold of...
LANGER: You see the nostrils?
ALAN ALDA: Yuck! Wait a minute! Look, with nostrils and everything…
LANGER: We made a scaffold and there's the little nostrils
there -- and that's pure cartilage.
ALAN ALDA: You could make it in big blocks and carve whatever shape
Exactly, exactly, that's the whole idea.
ALAN ALDA: Would you mind taking this back. I really don't
wanna…I mean it's alive, it's sort of alive.
LANGER: Yeah, sort of alive. We just wanted to give you a
flavor for it.
ALAN ALDA: Unbelievable! You bring in a nose! I can't get over
ALAN ALDA (Narration): In this MIT lab they're actually figuring
out how to make body parts.
RESEARCHER: First we make what we call a polymer scaffold,
and that's a piece of synthetic material that we can make
into the form of a sheet, or other three dimensional forms.
ALAN ALDA (Narration): Now we're making heart muscle, starting
with little clumps of synthetic fibers -- the polymer scaffold,
as they call it. Then the scaffold is bathed in living heart
cells. Bob Langer has pioneered this new field of tissue engineering.
BOB LANGER: She's trying to mimic, outside the body, what
actually happens inside the body. She's giving it the kind
of food it needs, the kind of structure it needs, and even
the kind of mixing, you know, that it may get inside the body.
ALAN ALDA: (Narration): If you get the conditions just right, you
can grow pieces of living heart tissue.
ALAN ALDA: I'm looking at something that's making heart. Does that
sort of strike you, every once it a while, that you're making
these things that used to be that if you lost it, that would
be the end.
BOB LANGER: Well that is what we want to do, you know. It
does strike us. What we hope is that some day we'll be able
to have a whole series of replacement parts for people so
that if they find a problem, we'll be able to help them.
ALAN ALDA: It's like an auto part shop, you know. I need a
new carburetor and you just go in and you drive out again.
I mean, this is... how many years away are we from having
a part shop for bodies, I mean where you can really just get
what you need. Is it ten years? Fifty years? A hundred years?
Must be hard to guess.
LANGER: Right I think it may depend on the part, you know.
Some of the easier parts like skin or cartilage, I think you
know that's probably five or ten years. Some of the harder
parts like heart, that may be many, many years away, fifty
or, you know, it's hard to know.
ALAN ALDA (Narration): Here, after about two weeks of growth, are
the pieces of new heart.
ALAN ALDA: They're under a microscope and then you can see
it on that monitor?
BOB LANGER: That's right, we have a microscope here and then
basically they're on the monitor and you can see them beating
ALAN ALDA: That's not the dish shaking, those are separate
LANGER: Right. Say, take a look right down here, for example,
or here. And these are individual heart muscle cells, and
they're just beating.
ALAN ALDA: Is there any way you could make use of that right now,
in a heart?
LANGER: It's too early to do that now, but some day what I
expect is that we could make a sheet of this, you know, and
make cardiac muscle. And some day, if we have the right type
of cells to actually transplant that onto a patient. You know
if they have, er, if some of their heart muscle's damaged.
ALDA (Narration): Right now they're working with animal cells,
but Bob Langer's hope is not at all far-fetched. Take a look
at one of those pieces of heart as they give it an EKG, like
a regular heart checkup you might get from your doctor. The
new tissue transmits heart beats exactly as it should. With
tissue engineering advancing rapidly, the search is on for
a reliable source of human cells to grow parts from. I'm visiting
Michael West at his company, Advanced Cell Technology. He's
aiming to make any kind of cell required -- heart, liver,
skin, you name it -- starting from the kind of cell we all
came from. They're called stem cells. Stem cells are the first
cells that grow as an embryo develops. All body parts are
derived from them, so the idea is to grow human stem cells,
inside cow eggs.
ALAN ALDA: Go straight in?
Yeah straight in.
ALAN ALDA (Narration): The technique is just like the one used
to clone Dolly the sheep. First I have to pierce the cow egg
and suck out the nucleus, containing the cow's genetic material.
There's a syringe next to your hand now. Turn it.
ALAN ALDA: There it is. Here it comes. Watch this, watch this guys.
This is good. This is good. Have I got it?
Go back a little bit more
ALAN ALDA: OK. Got it. Got it.
SCIENTIST: Perfect. Right there is perfect.
ALAN ALDA (Narration): Next I pick up a human cell -- this one's
a skin cell. Now I slide the human cell into the cow egg.
This is startling research -- producing human cells inside
animal eggs is an unprecedented idea.
ALAN ALDA: It's amazing
that you can get these human cells to grow inside the cow
egg. It's amazing to me. Why don't you use a human egg to
WEST: This is potentially a technology that could be used
to treat upwards of half of all healthcare problems. You'd
make beta cells for diabetes, or cartilage cells for arthritis,
and so on. There's literally millions of people that would
need the technology, and so you'd need millions of human egg
cells. And they're simply not available.
ALAN ALDA (Narration): At the end there's a little electric
shock, which stimulates the human nucleus to start dividing
inside the shelter of the cow egg. And the human stem cells
multiply. The next step has to be signaling the stem cells
to make particular cells, like heart or cartilage. scientists
are beginning to do that, but isn't this all a bit scary?
ALAN ALDA: Is there anything in the cow egg that makes... that
gives a cow any of its characteristics that could get into
the human cells, or mix with them in some way, so that you'd
wind up with some cow characteristics of any kind, with human
characteristics in these cells? Do you know that can't happen?
WEST: There's the possibility that the mitochondria could
live on. They're little what we call organelles within the
ALAN ALDA: Yeah. That's what we get the energy from.
MICHAEL WEST: Yes. Little batteries. They have they're own
DNA. But all of our information that we have in our hands
today would suggest that those cannot survive, so that the
cow mitochondria will die, and that the human mitochondria
then will live on. And so, our belief is that the cells eventually
will become entirely human.
ALAN ALDA (Narration): Fully expecting that one day engineered
human cells and body parts will be available,
VACANTI:, a pediatric transplant surgeon at Mass General in
Boston, is developing medical technologies to use the new
materials. They're working, for example, on a way to implant
replacement cells in a damaged heart, using a special gel.
VACANTI: It's an interesting plastic material that turns into,
on specific signaling, it'll turn into something that sort
of feels like jello
ALAN ALDA: So it starts out one way, and then it turns into jello?
ALAN ALDA: Is there something about this gel that's allowing
you to do something that you never did before?
VACANTI: Yes, the reason we use a gel is because it allows
the cells to align very closely to one another and talk to
each other. And once they can start talking to each other,
they actually then start forming new tissue.
ALAN ALDA (Narration): Right now they're using the gel to implant
new mouse heart cells, under the same conditions they'd use
VACANTI: So here what we're going to do is actually take this
preparation that we've made and put it in the heart muscle.
ALAN ALDA: So you want to see if you can get these cells that you're
injecting to actually merge with the existing heart cells?
VACANTI: Exactly right.
ALAN ALDA (Narration): This is the kind of technique that Dr. Vacanti
hopes will eventually relieve the widespread and tragic shortage
of transplant organs that exists right now. So far it's looking
ALAN ALDA: Now is this an intestine that you've allowed to grow
VACANTI: Yeah, actually what we're gonna see here is a piece
of new intestine that's been tissue engineered, and has been
back in the animal now for three weeks.
ALAN ALDA (Narration): Replacement intestine, liver, cartilage,
heart valves, even heart muscle. One day we're going to have
spare parts grown just for you, starting with your own stem
cells, so there'll be no rejection problems. And no doubt
as a result, we're going to live longer.
IT OR LOSE IT
ALAN ALDA: Now you walk like this every day?
ALAN ALDA (Narration): Our final segment is about how to be
successful at being old. Before long, many of us really could
find ourselves living to 150, 200, who knows? But can we get
there without losing our mental abilities, so that we can
enjoy our longer lives?
RAWSON:, Harvard's boxing coach, is not quite there yet -
he's 92. But what a 92.
TOMMY RAWSON: And this is what they have to do. One, two.
One, two, bom.
ALAN ALDA (Narration): Throughout his life, boxing has always kept
Tommy on his toes.
RAWSON: You get something in your mind. You want to take and
try to hit a man with a left hook. And if he's got a good
guard, keeps his hands up, then you don't use that. Then you
got to take and try the right hand.
ALAN ALDA: The combination of your mind working quickly and your
hands and feet working quickly. That's. Most people don't
do that. They don't coordinate those things the way you do.
RAWSON: That's what you have to do to be successful, I'd say.
The feet have to be working with the hands.
ALAN ALDA (Narration): As we'll see, keeping active is the
key to keeping the mind going strong.
RAWSON: One, two, three.
ALBERT: Just look and try to remember.
ALAN ALDA (Narration): Mass General psychologist, Marilyn
Albert, has been investigating what happens to people's thinking
abilities as they get older.
ALAN ALDA: Get up on here?
ALAN ALDA (Narration): One of the most common problems in
the elderly is memory loss - and lately Marilyn's group has
been looking for changes in the brain which might account
for this loss. They're testing people of different ages, and
today it's my turn. A slide projector will beam photographs
onto a screen that I have to watch, while I'm inside an MRI
machine. As I stare at the pictures and try to form a memory
of them, the machine will detect which areas of the brain
I'm using. While I'm presented with these pictures, cross-section
../../../images of my brain instantly show up in the control
room. The light areas correspond to brain tissue, and dark
areas to fluid surrounding the brain.
ALAN ALDA: How is my brain?
MARYLIN ALBERT: Actually it looks very young.
ALAN ALDA: Yes? What could you see?
MARYLIN ALBERT: We were admiring it.
ALAN ALDA: Yeah, what could you see?
MARYLIN ALBERT: We could see that there isn't too much fluid.
As you get older, the brain tends to shrink a little bit and
gets a little bit more fluid, and yours looks very tightly
ALAN ALDA (Narration): Now we'll compare my brain to those of other
subjects. On average, Marilyn finds that people in their 20s
and 30s show intense activity right here, while they're forming
a memory of a picture. In contrast, people in their 80s tend
not to have that activity. I was happy to see that my brain
activity still looks pretty young.
ALAN ALDA: Now what is that activity, what is that associated with?
MARYLIN ALBERT: We think the neurons are firing. We're measuring
the activity of nerve cells in the brain.
ALAN ALDA: What does that mean? Does that mean that older
people have a harder time actually registering what they're
trying to remember? It's not just that they don't recall something.
They haven't got it in there in the first place?
MARYLIN ALBERT: That's right. We think what happens as you
get older is that it takes you longer to learn something new.
If you work hard and you remember it, and you learn it really
well, you remember it as well as somebody much, much younger
ALAN ALDA (Narration): Hard work seems to be the key to all
kinds of mental activity in old age, not just memory, as Marilyn
found out in a large study she helped organize.
Hi, Mrs. Ryan. How are you?
RYAN: Good, dear.
ALAN ALDA (Narration): The 10-year study followed 1200 people as
they made the transition from middle to old age. Every two
years, participants got a battery of tests - like this memory
challenge, where the object is to pick out the chip that has
just been placed on the board. The study tried to identify
factors which might explain why people like Mrs. Ryan remain
sharp even in their 80s, while others decline.
Great. How often do you read books, magazines or newspapers?
Do you do that 3 or more times a week? Once to twice a week?
RYAN: Three or more.
Three or more times. Do you do arts, crafts or other hobbies?
MRS. RYAN: Knitting
ALAN ALDA (Narration): They looked at thinking activity, and physical
And how many city blocks or their equivalent do you walk each
RYAN: Oh, about 30 I guess. Because I walk three hours every
ALAN ALDA (Narration): The results were unequivocal. If you maintain
good physical health, get moderate exercise and keep your
brain reasonably stimulated, you can stay mentally sharp.
If you don't do those things, you go down hill.
ALAN ALDA (Narration):Bill Greenough, at the University of Illinois,
has done a landmark experiment with rats which reveals what
mental and physical stimulation actually does for the brain.
Aging animals were let loose for one hour a day in a rat wonderland.
The toys were changed daily so every day, when the rats explored,
they got not just a physical workout, but an opportunity to
learn something new, as well. When compared to the brains
of elderly, unstimulated rats, the stimulated ones had much
denser neuron fibers, without the dying off usually seen in
older animals. And all these light shapes showed the stimulated
rats also had many more blood vessels nourishing their brains.
In effect, the stimulated elderly rats had brains that looked
GREENOUGH: We used to believe that the brain developed, then
it got done developing and the brain was stable, and then
eventually the brain began to get old and declined and would
deteriorate. We've found really that both those things are
wrong. If the brain is constantly challenged - both mentally
in terms of demanding problem solving tasks, and physically
in terms of physical exercise, then that brain seems to remain
remarkably stable. Not to show very much in the way of the
kind of declines that we often thought of as inevitable.
ALAN ALDA (Narration): The lives of real people back up this idea.
Take Catherine McCaig. Throughout her 103 years, she's been
reading, dancing, learning languages -- and making jokes.
ALAN ALDA: How long have you been playing piano?
McCAIG: I've never played the piano.
ALAN ALDA: How long have you been sitting at one of these and working
McCAIG: A hundred years.
ALAN ALDA: A hundred years? You started when you were...
McCAIG: And I still can't play.
ALAN ALDA: Did you drive a car?
McCAIG: I did.
ALAN ALDA: When did you start driving a car?
ALAN ALDA: The age of 79. And how long did you drive?
McCAIG: Ten years.
ALAN ALDA: Ten years. CATHERINE McCAIG: Yeah. And when I finished
driving, as I say, after going through the plate glass window.
ALAN ALDA: Tell me about that.
McCAIG: Have I got to?
ALAN ALDA: If you don't mind… What kind of a building was
CATHERINE McCAIG: Pardon?
ALAN ALDA: What kind of a building was it that you went into?
CATHERINE McCAIG: The bank.
ALAN ALDA: The bank?
McCAIG: Yes, and they thought it was an explosion.
ALAN ALDA: I can imagine.
McCAIG: They ran for their lives.
ALAN ALDA: So, you invented the drive-through window.
ALBERT: So now we know that the old saying "use it or lose
it" really is true.
ALAN ALDA: And it's like literally true.
Your brain starts to go away if you don't use it every day.
And every day is important.
ALBERT: I think so.
ALAN ALDA: You can't go away for a renaissance weekend once a year.
It's got to be every day.
ALBERT: Yes. And it's the things you do day to day. Not complicated,
you know, unusual things, but to make it part of your life.
ALAN ALDA (Narration): Nobody knows what would actually happen
to the brains of people who lived until 150 or 200 -- because
nobody has yet lived that long. But so far, there doesn't
seem to be any limit. As long as we keep stimulating our brains
with challenging hobbies and jobs, and remain physically active,
we can probably retain our mental capabilities, no matter
how old we get. We've seen in this program that science is
closing in on the secrets of aging. For the first time in
human history, we may be able to deliberately extend our lifespans.
Maybe we'll do it by restricting our calorie intake... Or
by renewing the telomeres that limit how many times our cells
can divide... By manipulating the genes which govern lifespan...
Or by growing spare parts for our bodies. However we do it,
it looks like its really going to happen- and soon too.