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Where does the end begin?
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Well, for me, it all began
with this little fellow.
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This adorable organism --
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well, I think it's adorable --
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is called Tetrahymena
and it's a single-celled creature.
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It's also been known as pond scum.
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So that's right, my career
started with pond scum.
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Now, it was no surprise
I became a scientist.
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Growing up far away from here,
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as a little girl I was deadly curious
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about everything alive.
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I used to pick up lethally poisonous
stinging jellyfish and sing to them.
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And so starting my career,
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I was deadly curious
about fundamental mysteries
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of the most basic building blocks of life,
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and I was fortunate to live in a society
where that curiosity was valued.
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Now, for me, this little
pond scum critter Tetrahymena
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was a great way to study
the fundamental mystery
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I was most curious about:
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those bundles of DNA
in our cells called chromosomes.
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And it was because I was curious
about the very ends of chromosomes,
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known as telomeres.
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Now, when I started my quest,
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all we knew was that they helped
protect the ends of chromosomes.
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It was important when cells divide.
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It was really important,
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but I wanted to find out
what telomeres consisted of,
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and for that, I needed a lot of them.
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And it so happens
that cute little Tetrahymena
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has a lot of short linear chromosomes,
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around 20,000,
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so lots of telomeres.
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And I discovered that telomeres
consisted of special segments
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of noncoding DNA right
at the very ends of chromosomes.
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But here's a problem.
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Now, we all start life as a single cell.
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It multiples to two.
Two becomes four. Four becomes eight,
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and on and on to form
the 200 million billion cells
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that make up our adult body.
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And some of those cells
have to divide thousands of times.
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In fact, even as I stand here before you,
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all throughout my body,
cells are furiously replenishing
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to, well, keep me
standing here before you.
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So every time a cell divides,
all of its DNA has to be copied,
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all of the coding DNA
inside of those chromosomes,
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because that carries
the vital operating instructions
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that keep our cells in good working order,
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so my heart cells can keep a steady beat,
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which I assure you
they're not doing right now,
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and my immune cells
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can fight off bacteria and viruses,
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and our brain cells
can save the memory of our first kiss
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and keep on learning throughout life.
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But there is a glitch
in the way DNA is copied.
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It is just one of those facts of life.
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Every time the cell divides
and the DNA is copied,
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some of that DNA from the ends
gets worn down and shortened,
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some of that telomere DNA.
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And think about it
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like the protective caps
at the ends of your shoelace.
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And those keep the shoelace,
or the chromosome, from fraying,
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and when that tip
gets too short, it falls off,
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and that worn down telomere
sends a signal to the cells.
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"The DNA is no longer being protected."
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It sends a signal. Time to die.
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So, end of story.
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Well, sorry, not so fast.
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It can't be the end of the story,
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because life hasn't died
off the face of the earth.
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So I was curious:
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if such wear and tear is inevitable,
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how on earth does Mother Nature make sure
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we can keep our chromosomes intact?
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Now, remember that little
pond scum critter Tetrahymena?
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The craziest thing was,
Tetrahymena cells never got old and died.
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Their telomeres weren't shortening
as time marched on.
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Sometimes they even got longer.
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Something else was at work,
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and believe me, that something
was not in any textbook.
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So working in my lab with
my extraordinary student Carol Greider --
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and Carol and I shared
the Nobel Prize for this work --
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we began running experiments
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and we discovered
cells do have something else.
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It was a previously undreamed-of enzyme
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that could replenish,
make longer, telomeres,
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and we named it telomerase.
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And when we removed
our pond scum's telomerase,
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their telomeres ran down and they died.
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So it was thanks
to their plentiful telomerase
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that our pond scum critters never got old.
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OK, now, that's
an incredibly hopeful message
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for us humans to be
receiving from pond scum,
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because it turns out
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that as we humans age,
our telomeres do shorten,
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and remarkably,
that shortening is aging us.
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Generally speaking,
the longer your telomeres,
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the better off you are.
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It's the overshortening of telomeres
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that leads us to feel and see
signs of aging.
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My skin cells start to die
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and I start to see fine lines, wrinkles.
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Hair pigment cells die.
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You start to see gray.
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Immune system cells die.
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You increase your risks of getting sick.
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In fact, the cumulative research
from the last 20 years
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has made clear that telomere attrition
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is contributing to our risks
of getting cardiovascular diseases,
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Alzheimer's, some cancers and diabetes,
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the very conditions many of us die of.
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And so we have to think about this.
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What is going on?
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This attrition,
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we look and we feel older, yeah.
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Our telomeres are losing
the war of attrition faster.
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And those of us who feel youthful longer,
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it turns out our telomeres
are staying longer
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for longer periods of time,
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extending our feelings of youthfulness
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and reducing the risks
of all we most dread
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as the birthdays go by.
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OK,
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seems like a no-brainer.
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Now, if my telomeres are connected
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to how quickly
I'm going to feel and get old,
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if my telomeres can be
renewed by my telomerase,
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then all I have to do to reverse
the signs and symptoms of aging
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is figure out where to buy
that Costco-sized bottle
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of grade A organic
fair trade telomerase, right?
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Great! Problem solved.
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(Applause)
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Not so fast, I'm sorry.
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Alas, that's not the case.
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OK. And why?
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It's because human genetics has taught us
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that when it comes to our telomerase,
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we humans live on a knife edge.
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OK, simply put,
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yes, nudging up telomerase
does decrease the risks of some diseases,
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but it also increases the risks
of certain and rather nasty cancers.
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So even if you could buy
that Costco-sized bottle of telomerase,
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and there are many websites
marketing such dubious products,
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the problem is you could
nudge up your risks of cancers.
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And we don't want that.
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Now, don't worry,
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and because, while I think
it's kind of funny that right now,
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you know, many of us may be thinking,
well, I'd rather be like pond scum.
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(Laughter)
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There is something for us humans
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in the story of telomeres
and their maintenance.
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But I want to get one thing clear.
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It isn't about enormously
extending human lifespan
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or immortality.
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It's about health span.
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Now, health span is the number
of years of your life
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when you're free of disease,
you're healthy, you're productive,
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you're zestfully enjoying life.
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Disease span, the opposite of health span,
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is the time of your life
spent feeling old and sick and dying.
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So the real question becomes,
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OK, if I can't guzzle telomerase,
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do I have control
over my telomeres' length
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and hence my well-being, my health,
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without those downsides of cancer risks?
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OK?
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So, it's the year 2000.
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Now, I've been minutely scrutinizing
little teeny tiny telomeres
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very happily for many years,
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when into my lab walks
a psychologist named Elissa Epel.
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Now, Elissa's expertise is in the effects
of severe, chronic psychological stress
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on our mind's and our body's health.
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And there she was standing in my lab,
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which ironically overlooked
the entrance to a mortuary, and --
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(Laughter)
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And she had a life-and-death
question for me.
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"What happens to telomeres
in people who are chronically stressed?"
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she asked me.
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You see, she'd been studying caregivers,
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and specifically mothers of children
with a chronic condition,
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be it gut disorder,
be it autism, you name it --
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a group obviously under enormous
and prolonged psychological stress.
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I have to say, her question
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changed me profoundly.
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See, all this time
I had been thinking of telomeres
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as those miniscule
molecular structures that they are,
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and the genes that control telomeres.
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And when Elissa asked me
about studying caregivers,
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I suddenly saw telomeres
in a whole new light.
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I saw beyond the genes and the chromosomes
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into the lives of the real people
we were studying.
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And I'm a mom myself,
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and at that moment,
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I was struck by the image of these women
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dealing with a child with a condition
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very difficult to deal with,
often without help.
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And such women, simply,
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often look worn down.
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So was it possible their telomeres
were worn down as well?
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So our collective curiosity
went into overdrive.
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Elissa selected for our first study
a group of such caregiving mothers,
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and we wanted to ask:
What's the length of their telomeres
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compared with the number of years
that they have been caregiving
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for their child with a chronic condition?
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So four years go by
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and the day comes
when all the results are in,
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and Elissa looked down
at our first scatterplot
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and literally gasped,
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because there was a pattern to the data,
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and it was the exact gradient
that we most feared might exist.
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It was right there on the page.
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The longer, the more years that is,
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the mother had been
in this caregiving situation,
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no matter her age,
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the shorter were her telomeres.
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And the more she perceived
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her situation as being more stressful,
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the lower was her telomerase
and the shorter were her telomeres.
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So we had discovered something unheard of:
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the more chronic stress you are under,
the shorter your telomeres,
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meaning the more likely you were
to fall victim to an early disease span
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and perhaps untimely death.
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Our findings meant
that people's life events
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and the way we respond to these events
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can change how you
maintain your telomeres.
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So telomere length wasn't
just a matter of age counted in years.
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Elissa's question to me,
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back when she first came to my lab,
indeed had been a life-and-death question.
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Now, luckily, hidden
in that data there was hope.
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We noticed that some mothers,
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despite having been carefully caring
for their children for many years,
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had been able to maintain their telomeres.
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So studying these women closely revealed
that they were resilient to stress.
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Somehow they were able
to experience their circumstances
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not as a threat day in and day out
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but as a challenge,
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and this has led to a very important
insight for all of us:
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we have control over the way we age
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all the way down into our cells.
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OK, now our initial curiosity
became infectious.
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Thousands of scientists
from different fields
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added their expertise
to telomere research,
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and the findings have poured in.
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It's up to over 10,000
scientific papers and counting.
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So several studies
rapidly confirmed our initial finding
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that yes, chronic stress
is bad for telomeres.
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And now many are revealing
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that we have more control
over this particular aging process
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than any of us could ever have imagined.
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A few examples:
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a study from the University
of California, Los Angeles
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of people who are caring
for a relative with dementia, long-term,
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and looked at their caregiver's
telomere maintenance capacity
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and found that it was improved
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by them practicing a form of meditation
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for as little as 12 minutes
a day for two months.
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Attitude matters.
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If you're habitually a negative thinker,
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you typically see a stressful situation
with a threat stress response,
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meaning if your boss wants to see you,
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you automatically think,
"I'm about to be fired,"
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and your blood vessels constrict,
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and your level of the stress
hormone cortisol creeps up,
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and then it stays up,
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and over time, that persistently
high level of the cortisol
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actually damps down your telomerase.
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Not good for your telomeres.
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On the other hand,
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if you typically see something stressful
as a challenge to be tackled,
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then blood flows to your heart
and to your brain,
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and you experience a brief
but energizing spike of cortisol.
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And thanks to that habitual
"bring it on" attitude,
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your telomeres do just fine.
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So ...
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What is all of this telling us?
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Your telomeres do just fine.
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You really do have power
to change what is happening
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to your own telomeres.
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But our curiosity
just got more and more intense,
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because we started to wonder,
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what about factors outside our own skin?
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Could they impact
our telomere maintenance as well?
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You know, we humans
are intensely social beings.
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Was it even possible
that our telomeres were social as well?
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And the results have been startling.
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As early as childhood,
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emotional neglect, exposure to violence,
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bullying and racism
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all impact your telomeres,
and the effects are long-term.
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Can you imagine the impact on children
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of living years in a war zone?
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People who can't trust their neighbors
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and who don't feel safe
in their neighborhoods
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consistently have shorter telomeres.
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So your home address
matters for telomeres as well.
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On the flip side,
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tight-knit communities,
being in a marriage long-term,
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and lifelong friendships, even,
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all improve telomere maintenance.
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So what is all this telling us?
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It's telling us that I have the power
to impact my own telomeres,
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and I also have the power to impact yours.
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Telomere science has told us
just how interconnected we all are.
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But I'm still curious.
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I do wonder
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what legacy all of us
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will leave for the next generation?
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Will we invest
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in the next young woman or man
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peering through a microscope
at the next little critter,
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the next bit of pond scum,
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curious about a question
we don't even know today is a question?
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It could be a great question
that could impact all the world.
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And maybe, maybe you're curious about you.
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Now that you know
how to protect your telomeres,
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are you curious what are you going to do
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with all those decades
of brimming good health?
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And now that you know you could impact
the telomeres of others,
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are you curious
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how will you make a difference?
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And now that you know the power
of curiosity to change the world,
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how will you make sure
that the world invests in curiosity
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for the sake of the generations
that will come after us?
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Thank you.
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(Applause)