TEDGlobal 2011
Cynthia Kenyon: Experiments that hint of longer lives
Cynthia Kenyon: Experimentos que suxiren vidas lonxevas
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Que é o que controla o envellecemento? A bioquímica Cynthia Kenyon atopou unha simple mutación xenética que pode duplicar o tempo de vida dun simple verme, C. elegans. As leccións dese descubrimento, e outros, sinalan a como algún día poderiamos alongar significativamente a vida humana xuvenil.
Cynthia Kenyon - Biochemist, geneticist
When it comes to aging well, having “good genes” (or rather, mutant ones) is key, says Cynthia Kenyon. She unlocked the genetic secret of longevity in roundworms — and now she’s working to do the same for humans. Full bio
When it comes to aging well, having “good genes” (or rather, mutant ones) is key, says Cynthia Kenyon. She unlocked the genetic secret of longevity in roundworms — and now she’s working to do the same for humans. Full bio
Double-click the English transcript below to play the video.
00:15
Have you ever wanted to stay young a little longer
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Algunha vez quixestes ser mozos un pouco mais
00:18
and put off aging?
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e retrasar o envellecemento?
00:20
This is a dream of the ages.
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Este foi o sono de tódolos tempos.
00:23
But scientists have for a long time
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Pero durante moito tempo os científicos
00:25
thought this just was never going to be possible.
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pensaron que nunca sería posíbel.
00:27
They thought you just wear out, there's nothing you can do about it --
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Pensaban que un se desgasta e non hai nada que se poida facer...
00:30
kind of like an old shoe.
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como cun zapato vello.
00:32
But if you look in nature,
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Pero se miramos a natureza
00:34
you see that different kinds of animals
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podemos ver que distintos tipos de animais
00:36
can have really different lifespans.
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teñen esperanzas de vida moi diferentes.
00:38
Now these animals are different from one another,
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Estes animais son diferentes uns doutros
00:40
because they have different genes.
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porque teñen xenes distintos.
00:42
So that suggests
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Isto suxire
00:44
that somewhere in these genes, somewhere in the DNA,
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que nalgún lugar deses xenes, nalgún lugar do ADN,
00:46
are genes for aging,
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existen xenes para o envellecemento,
00:48
genes that allow them to have different lifespans.
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xenes que lles permiten ter distintas esperanzas de vida.
00:50
So if there are genes like that,
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Se hai xenes coma eses,
00:52
then you can imagine that,
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entón podemos imaxinar que,
00:54
if you could change one of the genes in an experiment,
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se poideramos trocar un deses xenes nun experimento,
00:56
an aging gene,
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un xen do envellecemento,
00:58
maybe you could slow down aging and extend lifespan.
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quizais se retrasaría o envellecemento e aumentaría a esperanza de vida.
01:01
And if you could do that, then you could find the genes for aging.
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Se se puidera, entón poderiamos atopar xenes para o envellecemento.
01:04
And if they exist and you can find them,
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E se existen e podemos atopalos,
01:06
then maybe one could eventually do something about it.
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se cadra un podería facer algo con iso.
01:09
So we've set out to look for genes that control aging.
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Así, propuxémonos buscar xenes que controlaran o envellecemento.
01:12
And we didn't study any of these animals.
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E non estudamos ningún deses animais.
01:15
Instead, we studied a little, tiny, round worm called C. elegans,
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En troques, estudamos un pequen e redondo verme chamado C. elegans,
01:18
which is just about the size of a comma in a sentence.
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do tamano dunha comiña nunha oración.
01:21
And we were really optimistic that we could find something
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Eramos moi optimistas de que encontrariamos algo
01:24
because there had been a report of a long-lived mutant.
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porque houbo un informe dun mutante de vida lonxeva.
01:27
So we started to change genes at random,
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Así que comezamos a trocar xenes ó azar,
01:29
looking for long-lived animals.
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andando á procura de animais lonxevos.
01:31
And we were very lucky to find
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E tivemos a sorte de atopar
01:33
that mutations that damage one single gene called daf-2
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que mutacións que danan un só xen chamado daf-2
01:37
doubled the lifespan of the little worm.
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dobran a esperanza de vida do vermiño..
01:40
So you can see in black, after a month --
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Entón podedes velo en negro, despois dun mes;
01:42
they're very short-lived; that's why we like to study them
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teñen unha vida moi curta, por iso queriamos empregalos
01:44
for studies of aging --
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para estudos de envellecemento;
01:46
in black, after a month, the normal worms are all dead.
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en negro, despois dun mes, os vermes estaban todos mortos.
01:49
But at that time,
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Pero á vez,
01:51
most of the mutant worms are still alive.
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moitos dos vermes mutantes seguían vivos.
01:53
And it isn't until twice as long
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E non morreron ata que pasou
01:55
that they're all dead.
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o dobre de tempo.
01:57
And now I want to show what they actually look like in this movie here.
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E agora quero mostrarvos o que se ve verdadeiramente nesta filme.
02:00
So the first thing you're going to see
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A primeria cousa que ides ver
02:02
is the normal worm
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é o verme normal
02:04
when it's about college student age -- a young adult.
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cando ten máis ou menos a idade dun estudante, un xoven adulto.
02:07
It's quite a cute little fellow.
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É un mociño moi lindo.
02:10
And next you're going to see the long-lived mutant when it's young.
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E agora ides ver o mutante de vida longa cando é xove.
02:13
So this animal is going to live twice as long.
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Por tanto, este animal vai vivir o dobre de tempo.
02:15
Is it miserable? It doesn't seem to be.
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É miserábel? Non o parece.
02:17
It's active. You can't tell the difference really.
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É activo. Non se atopan realmente diferenzas.
02:20
And they can be completely fertile --
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E son totalmente fértis...
02:22
have the same number of progeny as the normal worms do.
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teñen o mesmo número de descendencia cos vermes normais.
02:24
Now get out your handkerchiefs here.
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Agora sacade os vosos panos.
02:26
You're going to see, in just two weeks,
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Ides ver, que en só dúas semanas,
02:28
the normal worms are old.
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os vermes normais son vellos.
02:30
You can see the little head moving down at the bottom there.
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Podedes ver a súa pequena cabeza movéndose alí no fondo.
02:33
But everything else is just lying there.
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Pero todo o demáis está alí quieto.
02:35
The animal's clearly in the nursing home.
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O animal está claramente no asilo.
02:37
And if you look at the tissues of the animal, they're starting to deteriorate.
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E se observades os texidos do animal, veredes que empezan a se deteriorar.
02:40
You know, even if you've never seen one of these little C. elegans --
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Podedes saber, incluso se nunca vistes un deses pequenos C. elegans,
02:42
which probably most of you haven't seen one --
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probablemente a maioría de vós non vistes un,
02:44
you can tell they're old -- isn't that interesting?
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podedes dicir que son vellos, non é interesante?
02:47
So there's something about aging that's kind of universal.
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Polo tanto, hai algo universal en canto o envellecemento.
02:50
And now here is the daf-2 mutant.
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E agora aquí tedes o mutante daf-2.
02:53
One gene is changed out of 20,000, and look at it.
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Un dos 20,000 xenes cambiou, e mirádeo.
02:55
It's the same age, but it's not in the nursing home;
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Ten a mesma idade, sen embargo non está no asilo;
02:58
it's going skiing.
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está indo a esquiar.
03:01
This is what's really cool: it's aging more slowly.
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Isto é o que máis mola: o envellecemento vai máis lento.
03:04
It takes this worm two days
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Este verme tarda dous días
03:06
to age as much as the normal worm ages in one day.
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en envellecer o que un verme normal envellece nun día.
03:08
And when I tell people about this,
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E cando falo coa xente disto,
03:10
they tend to think of maybe an 80 or 90 year-old person
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eles tenden a pensar en persoas de 80 ou 90 anos
03:14
who looks really good for being 90 or 80.
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que se ven demasiado ben para ter 90 ou 80.
03:16
But it's really more like this:
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Pero é mais bes así:
03:18
let's say you're a 30 year-old guy -- or in your 30s --
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pensemos que sodes mozos de 30 anos, mais ou menos,
03:21
and you're a bachelor and you're dating people.
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solteiros e saíndo con xente.
03:23
And you meet someone you really like, you get to know her.
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E vos atopades con alguén que realmente vos gusta, e queres coñecela.
03:26
And you're in a restaurant, and you say, "Well how old are you?"
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Estades nun restaurante, e dicis: "Bueno, e cantos anos tes?"
03:29
She says, "I'm 60."
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Ela di, "teño 60 anos."
03:31
That's what it's like. And you would never know.
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Asi é como é. E nunca o saberiades.
03:33
You would never know, until she told you.
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Non vos dariades conta, ata que ela volo dixera.
03:35
(Laughter)
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(Gargalladas)
03:39
Okay.
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Dacordo.
03:41
So what is the daf-2 gene?
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Entón que é o xen daf-2?
03:43
Well as you know, genes, which are part of the DNA,
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Ben, como sabedes, os xenes, que son parte do DNA,
03:45
they're instructions to make a protein that does something.
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son coma instrucións para crear unhaa proteina que fai algo.
03:48
And the daf-2 gene
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E o xen daf-2
03:50
encodes a hormone receptor.
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codifica un receptor hormonal.
03:52
So what you see in the picture there
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Así que o que vedes nese debuxo de ahí
03:54
is a cell with a hormone receptor in red
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é una célula cun receptor hormonal en vermello
03:56
punching through the edge of the cell.
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atravesando o borde da célula.
03:58
So part of it is like a baseball glove.
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Así que parte dela é coma unha luva de béisbol.
04:00
Part of it's on the outside,
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Parte del está para afora,
04:02
and it's catching the hormone as it comes by in green.
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e está collendo a hormona que se aproxima, o verde.
04:04
And the other part is on the inside
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E a outra parte está no interior
04:06
where it sends signals into the cell.
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enviando señais dentro da célula.
04:08
Okay, so what is the daf-2 receptor
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Ben, entón que lle di o receptor daf-2
04:10
telling the inside of the cell?
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ó interior da célula?
04:12
I just told you that, if you make a mutation in the daf-2 gene cell,
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Xusto o que vos contei, se se fai unha mutación no xen daf-2,
04:15
that you get a receptor that doesn't work as well;
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obtense un receptor que non funciona tan ben;
04:17
the animal lives longer.
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e o animal vive máis tempo.
04:19
So that means that the normal function of this hormone receptor
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Significa que a función normal deste receptor hormonal
04:22
is to speed up aging.
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é acelerar o envellecemento.
04:24
That's what that arrow means.
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Iso significa esa frecha.
04:26
It speeds up aging. It makes it go faster.
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Acelera o envellecemento. Fai que sexa máis rápido.
04:28
So it's like the animal has the grim reaper inside of itself,
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É coma se o animal tivera á parca dentro del,
04:30
speeding up aging.
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acelerando o envellecemento.
04:32
So this is altogether really, really interesting.
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Así que isto é un conxunto moi, moi interesante.
04:35
It says that aging is subject to control by the genes,
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Dinos que o envellecemento está suxeito ó control xenético,
04:38
and specifically by hormones.
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e especialmente das hormonas.
04:41
So what kind of hormones are these?
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Que tipo de hormonas son estas?
04:43
There's lots of hormones. There's testosterone, adrenalin.
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Hai moitas hormonas. Testosterona, adrenalina...
04:45
You know about a lot of them.
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Sabedes bastante delas.
04:47
These hormones are similar
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Estas hormonas son similares
04:49
to hormones that we have in our bodies.
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ás hormonas que temos nos nosos corpos.
04:51
The daf-2 hormone receptor
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O receptor hormonal daf-2
04:53
is very similar to the receptor
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é moi semellante ó receptor
04:55
for the hormone insulin and IGF-1.
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para a hormona insulina e a IGF-2
04:58
Now you've all heard of at least insulin.
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Todos oistes falar polo menos da insulina.
05:00
Insulin is a hormone that promotes the uptake of nutrients
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É unha hormona que promove a adquisición de nutrintes
05:03
into your tissues after you eat a meal.
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ó longo dos tecidos despois de comer.
05:05
And the hormone IGF-1 promotes growth.
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E a hormona IGF-2 promove o crecemento.
05:08
So these functions were known for these hormones for a long time,
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Conociamos estas hormonas dende fai tempo,
05:11
but our studies suggested
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pero os nosos estudos suxiren
05:13
that maybe they had a third function that nobody knew about --
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que quizais teñan unha terceira función que ninguén saiba;
05:15
maybe they also affect aging.
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se cadra tamén afectan ó envellecemento.
05:17
And it's looking like that's the case.
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E parece que así é.
05:19
So after we made our discoveries with little C. elegans,
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Despois dos descubrimentos co C. elegans,
05:22
people who worked on other kinds of animals
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as persoas que traballaban con outros tipos de animais
05:24
started asking, if we made the same daf-2 mutation,
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comezaron a preguntarse, se facemos a mesma mutación daf-2,
05:27
the hormone receptor mutation, in other animals,
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a mutación do receptor hormonal, noutros animais,
05:30
will they live longer?
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vivirán máis tempo?
05:32
And that is the case in flies.
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É así no caso das moscas.
05:34
If you change this hormone pathway in flies, they live longer.
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Se trocamos esta ruta hormonal nas moscas, viven máis tempo.
05:37
And also in mice -- and mice are mammals like us.
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E tamén nos ratos... que son mamíferos coma nós.
05:40
So it's an ancient pathway,
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Entón é unha ruta antigua,
05:42
because it must have arisen a long time ago in evolution
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porque debeu surxir fai moito tempo na evolución
05:44
such that it still works in all these animals.
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para que siga funcionando en todos estes animais.
05:47
And also, the common precursor also gave rise to people.
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Tamén, o precursor común deu orixe ás persoas.
05:50
So maybe it's working in people the same way.
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Entón se cadra funciona nas persoas da mesma maneira.
05:52
And there are hints of this.
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E hai indicios que indican que si.
05:54
So for example, there was one study that was done
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Así que, por exemplo, fíxose un estudo
05:56
in a population of Ashkenazi Jews in New York City.
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nunha poboación de xudeus asquenazís de Nova Iorque.
05:59
And just like any population,
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E, coma calquera poboación,
06:01
most of the people live to be about 70 or 80,
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a maioría das persoas viven entre 70 e 80 anos,
06:04
but some live to be 90 or 100.
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pero algunhas viven ata 90 ou 100.
06:06
And what they found
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O que descubriron foi que
06:08
was that people who lived to 90 or 100
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era mais probable que as persoas que viviran
06:11
were more likely to have daf-2 mutations --
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ata os 90 ou 100 tiveran mutación daf-2,
06:14
that is, changes in the gene
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é dicir, cambios no xen
06:16
that encodes the receptor for IGF-1.
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que codifica o receptor de IGF-1.
06:18
And these changes made the gene not act as well
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Estes cambios fixeron que o xen non actuara tan ben
06:23
as the normal gene would have acted.
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como o faría o xen normal.
06:25
It damaged the gene.
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Danou ó xen.
06:27
So those are hints
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Polo tanto, eses son indicios
06:29
suggesting that humans are susceptible
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que suxiren que os humáns somos susceptibles
06:31
to the effects of the hormones for aging.
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ós efectos das hormonas no envellecemento.
06:33
So the next question, of course, is:
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A siguiente cuestión, desde logo, é:
06:35
Is there any effect on age-related disease?
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hai algún efecto nas enfermidades relacionadas coa idade?
06:38
As you age, you're much more likely
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Ó envellecer, é moito máis probable
06:40
to get cancer, Alzheimer's disease,
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padecer cancros, Alzheimer,
06:42
heart disease, all sorts of diseases.
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enfermidades cardíacas, todo tipo de enfermidades.
06:44
It turns out that these long-lived mutants
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Resulta que estes mutantes lonxevos
06:46
are more resistant to all these diseases.
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son máis resistentes a todas estas enfermidades.
06:48
They hardly get cancer,
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É raro que teñan cancro,
06:50
and when they do it's not as severe.
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e cando o teñen, non é tan grave.
06:52
So it's really interesting, and it makes sense in a way,
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É moi interesante, e en certa forma ten sentido,
06:54
that they're still young,
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que se ainda son mozos,
06:56
so why would they be getting diseases of aging until their old?
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non terán enfermidades da vellez ata que sexan vellos.
07:00
So it suggests
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Isto suxire
07:02
that, if we could have a therapeutic or a pill to take
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que, se tiveramos unha terapia ou unha pílula que tomar
07:05
to replicate some of these effects in humans,
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para replicar algúns destos efectos nos humáns,
07:07
maybe we would have a way
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quizais teriamos unha forma
07:09
of combating lots of different age-related diseases
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de combater distintas enfermidades relacionadas coa idade
07:11
all at once.
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ó memos tempo.
07:13
So how can a hormone ultimately affect the rate of aging?
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Como pode unha hormona afectar á tasa de envellecemento?
07:15
How could that work?
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Como podería funcionar iso?
07:17
Well it turns out that in the daf-2 mutants,
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Ben, resulta que nos mutantes daf-2,
07:20
a whole lot of genes are switched on in the DNA
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varios dos xenes actívanse no ADN
07:23
that encode proteins that protect the cells and the tissues,
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que codifica proteínas que protexen ás células e ós tecidos,
07:26
and repair damage.
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e reparan o dano.
07:28
And the way that they're switched on
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Actívanse mediante
07:31
is by a gene regulator protein called FOXO.
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unha proteína reguladora de xenes chamada FOXO.
07:34
So in a daf-2 mutant --
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Entón nun mutante daf-2...
07:36
you see that I have the X drawn here through the receptor.
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Vedes que teño unha X tachando o receptor.
07:38
The receptor isn't working as well.
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O receptor non está funcionando ben.
07:40
Under those conditions, the FOXO protein in blue
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Baixo esas condicións, a proteína FOXO en azul
07:43
has gone into the nucleus --
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pasou ó núcleo,
07:45
that little compartment there in the middle of the cell --
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ese pequeno compartimento no medio da célula,
07:47
and it's sitting down on a gene binding to it.
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e reposa sobre un xen enraizándose a él.
07:49
You see one gene. There are lots of genes actually that bind on FOXO.
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Vedes un xen. Hai varios xenes que se enlazan a FOXO.
07:51
And it's just sitting on one of them.
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E só se pousa sobre un deles.
07:53
So FOXO turns on a lot of genes.
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Así que FOXO encende varios xenes.
07:55
And the genes it turns on includes antioxidant genes,
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Entre os xenes que activa están os antioxidantes;
07:58
genes I call carrot-giver genes,
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xenes que chamo doadores-de-cenoria,
08:00
whose protein products
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cuxos produtos proteicos
08:02
actually help other proteins to function well --
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axudan a outras proteínas a funcionar ben,
08:04
to fold correctly and function correctly.
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a dobrarse correctamente e funcionar ben.
08:06
And it can also escort them to the garbage cans of the cell
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E poden tamén escoltalos cara o lixo da célula
08:09
and recycle them if they're damaged.
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e reclicalos se están danados.
08:11
DNA repair genes
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Os xenes reparadores de ADN
08:13
are more active in these animals.
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son moito máis activos nestes animais.
08:15
And the immune system is more active.
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E o sistema inmune está máis activo.
08:17
And many of these different genes, we've shown,
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Moitos destes xenes distintos, demostraramos,
08:20
actually contribute to the long lifespan of the daf-2 mutant.
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contribúen á vida lonxeva do mutante daf-2.
08:23
So it's really interesting.
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Isto é moi interesante.
08:25
These animals have within them
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Estes animais teñen dentro deles
08:27
the latent capacity to live much longer than they normally do.
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a capacidade latente de vivir moito máis do normal.
08:30
They have the ability
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Teñen a habilidade
08:32
to protect themselves from many kinds of damage,
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de protexerse de moitos tipos de dano,
08:34
which we think makes them live longer.
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e é o que cremos que os fai vivir máis.
08:37
So what about the normal worm?
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Que pasa logo co verme normal?
08:39
Well when the daf-2 receptor is active,
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Cando o receptor daf-2 está activo,
08:42
then it triggers a series of events
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desencadea unha serie de sucesos
08:44
that prevent FOXO
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que evitan que FOXO
08:46
from getting into the nucleus where the DNA is.
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entre no núcleo onde está o ADN.
08:49
So it can't turn the genes on.
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Non pode activar os xenes.
08:51
That's how it works. That's why we don't see the long lifespan,
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Así funciona. Por iso non vemos a lonxevidade,
08:53
until we have the daf-2 mutant.
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ata que temos ó mutante daf-2.
08:55
But what good is this for the worm?
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Logo que beneficio ten así o verme?
08:57
Well we think that insulin and IGF-1 hormones
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Pensamos que as hormonas insulina e IGF-1
09:00
are hormones that are particularly active
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están específicamente activas
09:02
under favorable conditions -- in the good times --
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baixo condicións favorables, nos bós tempos,
09:04
when food is plentiful and there's not a lot of stress in the environment.
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cando a comida é abundante e non hai estrés ambiental.
09:07
Then they promote the uptake of nutrients.
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Entón promoven a obtención de nutrintes.
09:09
You can store the food, use it for energy,
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Poden almacenar comida, usala para obter enerxía,
09:12
grow, etc.
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medrar, etc.
09:14
But what we think is that, under conditions of stress,
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Pero baixo condicións de estrés, parece que
09:17
the levels of these hormones drop --
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os niveis destas hormonas diminúen;
09:19
for example, having limited food supply.
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por exemplo, tendo unha fonte limitada de alimento.
09:22
And that, we think,
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E pensamos, que o animal
09:24
is registered by the animal as a danger signal,
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rexistra iso coma un sinal de perigo,
09:26
a signal that things are not okay
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un sinal de que as cousas non van ben
09:28
and that it should roll out its protective capacity.
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e de que debería poñerse en modo de protección.
09:31
So it activates FOXO, FOXO goes to the DNA,
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Por iso activa a FOXO, FOXO vai ó ADN,
09:34
and that triggers the expression of these genes
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e iso activa a expresión destes xenes
09:36
that improves the ability of the cell
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que melloran a habilidade da célula
09:38
to protect itself and repair itself.
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de protexerse e repararse a sí mesma.
09:40
And that's why we think the animals live longer.
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E pensamos que é por iso que os animais viven máis.
09:42
So you can think of FOXO
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Polo que poden pensar en FOXO
09:44
as being like a building superintendent.
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coma o porteiro do edificio.
09:47
So maybe he's a little bit lazy,
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Quizais sexa un pouco esaxerado
09:49
but he's there, he's taking care of the building.
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pero alí está, encárgase do edificio.
09:51
But it's deteriorating.
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Pero estase deteriorando.
09:53
And then suddenly, he learns that there's going to be a hurricane.
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E entón, subitamente, entérase de que ven o furacán.
09:56
So he doesn't actually do anything himself.
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Así que el non fai moito.
09:58
He gets on the telephone --
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Toma o teléfono,
10:00
just like FOXO gets on the DNA --
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coma FOXO toma o ADN,
10:02
and he calls up
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e chama
10:04
the roofer, the window person,
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ó reparador de tellados e fiestras,
10:06
the painter, the floor person.
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ó pintor, ó que pon os pisos...
10:09
And they all come and they fortify the house.
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E todos van fortifica-la vivenda.
10:11
And then the hurricane comes through,
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Logo chega o furacán,
10:13
and the house is in much better condition than it would normally have been in.
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e a casa está en mellor condición do que estaría normalmente.
10:15
And not only that, it can also just last longer,
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Non só iso, tamén pode durar máis,
10:18
even if there isn't a hurricane.
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aínda se non hai un furacán.
10:20
So that's the concept here
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Pensamos que esa é a idea,
10:22
for how we think this life extension ability exists.
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pensamos que así funciona esta extensión da vida.
10:26
Now the really cool thing about FOXO
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O xenial de FOXO
10:28
is that there are different forms of it.
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é que ten diferentes formas.
10:30
We all have FOXO genes,
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Todos temos xenes FOXO,
10:33
but we don't all have exactly the same form of the FOXO gene.
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pero non todos temos exactamente a mesma forma do xen FOXO.
10:36
Just like we all have eyes,
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Igual que todos temos ollos,
10:38
but some of us have blue eyes and some of us have brown eyes.
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pero algúns os temos azuis e outros marróns.
10:41
And there are certain forms of the FOXO gene
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Hai certas formas do xen FOXO
10:44
that have found to be more frequently present
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que se presentan con maior frecuencia
10:46
in people who live to be 90 or 100.
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en persoas que viven ata os 90 ou 100.
10:48
And that's the case all over the world,
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E é así en todo o mundo,
10:50
as you can see from these stars.
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como poden ver por estas estrelas.
10:52
And each one of these stars represents a population
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Cada unha resepresenta unha poboación
10:54
where scientists have asked,
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onde os científicos preguntaron:
10:56
"Okay, are there differences in the type of FOXO genes
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"Hai diferenzas no tipo de xen FOXO
10:58
among people who live a really long time?" and there are.
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entre as persoas que viven unha vida lonxeva?"; e hainas.
11:01
We don't know the details of how this works,
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Non coñecemos os detalles do funcionamento.
11:03
but we do know then
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pero si sabemos
11:05
that FOXO genes can impact
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que os xenes FOXO teñen un impacto
11:07
the lifespan of people.
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na lonxevidade das persoas.
11:09
And that means that, maybe if we tweak it a little bit,
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E iso quere dicir que, quizais se o modificamos un pouco,
11:12
we can increase the health and longevity of people.
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poderiamos incrementar a saúde e lonxevidade das persoas.
11:16
So this is really exciting to me.
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Isto é moi emocionante pra mín.
11:18
A FOXO is a protein that we found in these little, round worms
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Un FOXO é unha proteína que atopamos nestos vermes redondos
11:20
to affect lifespan,
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que afecta á lonxevidade,
11:22
and here it affects lifespan in people.
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e aquí afecta á lonxevidade das persoas.
11:24
So we've been trying in our lab now
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No laboratorio intentamos
11:26
to develop drugs
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desenvolver medicamentos
11:28
that will activate this FOXO cell
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que activen esta célula FOXO
11:30
using human cells now
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usando células humanas
11:32
in order to try and come up with drugs
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para intentar obter medicamentos
11:34
that will delay aging and age-related diseases.
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que retrasen o envellecemento e as enfermidades relacionadas.
11:37
And I'm really optimistic that this is going to work.
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Son moi optimista e penso que funcionará.
11:40
There are lots of different proteins that are known to affect aging.
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Hai moitas proteínas distintas e sábese que afectan ó envellecemento.
11:43
And for at least one of them, there is a drug.
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E para polo menos unha delas, hai un medicamento.
11:46
There's one called TOR, which is another nutrient sensor,
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É o chamado TOR, que é outro sensor de nutrientes,
11:48
like the insulin pathway.
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coma a ruta da insulina.
11:50
And mutations that damage the TOR gene --
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E as mutacións que danan ó xen TOR,
11:52
just like the daf-2 mutations --
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coma coas mutacións daf-2,
11:54
extend lifespan in worms
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extenden a esperanza de vida en vermes,
11:56
and flies and mice.
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moscas e ratos.
11:59
But in this case, there's already a drug called rapamycin
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Pero neste caso, hai un medicamento dispoñible, a rapamicina
12:01
that binds to the TOR protein
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que se enrraiza coa proteina TOR
12:03
and inhibits its activity.
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e inhibe a súa actividade
12:05
And you can take rapamycin and give it to a mouse --
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Pódese tomar rapamicina e dárllela a un rato,
12:08
even when it's pretty old, like age 60 for a human,
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ainda se é bastante vello, coma un humán ós 60,
12:10
that old for a mouse --
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o equivalente nun rato.
12:12
if you give the mouse rapamycin,
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Se lle damos ó rato rapamicina,
12:14
it will live longer.
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vivirá máis tempo.
12:16
Now I don't want you all to go out taking rapamycin.
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Tampouco quero que todos vaiades agora tomar rapamicina.
12:18
It is a drug for people,
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É un medicamento para as perosas,
12:20
but the reason is it suppresses the immune system.
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pero suprime o sistema inmune.
12:23
So people take it to prevent organ transplants from being rejected.
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Así que as persoas tómano para prever o rexeitamento de transplantes de órganos.
12:27
So this may not be the perfect drug
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NAsí que non é o medicamento perfeto
12:29
for staying young longer.
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para manterse xove por máis tempo.
12:31
But still, here in the year 2011,
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Pero aínda así, hoxe no 2011,
12:34
there's a drug that you can give to mice at a pretty old age
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hai unha droga que se lle pode dar ós ratos de idade avanzada
12:36
that will extend their lifespan,
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que alongará as súas vidas,
12:38
which comes out of this science
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o que resulta desta ciencia
12:40
that's been done in all these different animals.
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probada nestes animais.
12:42
So I'm really optimistic,
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Por iso son bastante optimista
12:44
and I think it won't be too long, I hope,
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e creo que non pasará moito tempo, espero,
12:46
before this age-old dream begins to come true.
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ata de que se faga realidade este sono da idade avanzada.
12:49
Thank you.
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Grazas.
12:51
(Applause)
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(Aplausos)
13:00
Matt Ridley: Thank you, Cynthia.
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Matt Ridley: Grazas, Cynthia.
13:03
Let me get this straight.
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A ver se o teño claro.
13:05
Although you're looking for a drug
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Anque estás na busca dun medicamento
13:07
that can solve aging
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que poida resolver o envellecemento
13:09
in old men like me,
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en homes vellos coma min.
13:12
what you could do now pretty well in the lab,
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Poderías agora facer no laboratorio,
13:15
if you were allowed ethically,
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se eticamente se permitira,
13:17
is start a human life from scratch
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unha vida humana desde cero
13:20
with altered genes that would make it live for a lot longer?
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con xenes alterados que fixeran que vivira mais tempo?
13:23
CK: Ah, so the kinds of drugs I was talking about
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CK: Ah, os medicamentos dos que vos falaba
13:26
would not change the genes,
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non cambiarían os xenes,
13:28
they would just bind to the protein itself
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senón que só se unirían á proteína mesma
13:31
and change its activity.
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para cambiar a súa actividade.
13:33
So if you stop taking the drug, the protein would go back to normal.
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Entón, se deixas de tomarlo, a proteína volve á normalidade.
13:36
You could change the genes in principle.
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Poderías cambiar xenes en principio.
13:39
There isn't the technology to do that.
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Pero non hai ningunha tecnoloxía para facelo.
13:41
But I don't think that's a good idea.
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Aínda que non creo que sexa unha boa idea.
13:43
And the reason is
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E a razón é
13:45
that these hormones,
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que estas hormonas
13:47
like the insulin and the IGF hormones and the TOR pathway,
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coma a hormona insulina e a IGF e a ruta de TOR,
13:50
they're essential.
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son esenciais.
13:52
If you knock them out completely, then you're very sick.
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Se as eliminas por completo, estarás moi enfermo.
13:55
So it might be that you would just have to fine tune it very carefully
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Terías que axustalo todo con moita precisión e coidado
13:58
to get the benefits without getting any problems.
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para conseguir os beneficios sen ter problemas.
14:01
And I think that's much better,
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E creo que é moito mellor,
14:03
that kind of control would be much better as a drug.
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ese tipo de control sería moito mellor coma medicamento.
14:05
And also, there are other ways of activating FOXO
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E tamén, hai outras formas de activar a FOXO
14:08
that don't even involve insulin or IGF-1
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que nin sequera fan intervir á insulina ou IGF-1
14:10
that might even be safer.
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iso podería ser aínda máis seguro.
14:12
MR: I wasn't suggesting that I was going to go and do it, but ...
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MR: Non estaba suxerindo que o fora a facer, pero...
14:15
(Laughter)
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(Gargalladas)
14:19
There's a phenomenon which you have written about and spoken about,
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Hai un fenómeno sobre o que escribiches e falaches,
14:23
which is a negligible senescence.
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unha senectude insignificante.
14:26
There are some creatures on this planet already
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Xa hai algúns seres neste planeta
14:28
that don't really do aging.
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que non envellecen.
14:31
Just move to one side for us, if you would.
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Achégate aquí un momento, por favor.
14:34
CK: There are. There are some animals that don't seem to age.
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CK: Hainos. Hai uns animais que aparentenemente non envellecen.
14:37
For example, there are some tortoises called Blanding's turtles.
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Por exemplo, están as chamadas tartarugas de Blanding.
14:41
And they grow to be about this size.
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Medran ata ser máis ou menos deste tamaño.
14:43
And they've been tagged, and they've been found to be 70 years old.
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Téñense etiquetado, e se atoparon exemplares de ata 70 anos.
14:46
And when you look at these 70 year-old turtles,
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E cando ves estas tartarugas de 70 anos,
14:48
you can't tell the difference, just by looking,
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a simple vista, non atopas diferenzas
14:51
between those turtles and 20 year-old turtles.
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entre esas tartarugas e unhas de 20 anos.
14:53
And the 70 year-old ones,
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E as de 70 anos,
14:55
actually they're better at scouting out the good nesting places,
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de feito son mellores para buscar lugares de anidamento,
14:58
and they also have more progeny every year.
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e tamén teñen máis descendencia cada ano.
15:01
And there are other examples of these kinds of animals,
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Hai outros exemplos deste tipo de animais,
15:04
like turns, certain kinds of birds are like this.
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de forma similar, algúns tipos de aves son así.
15:07
And nobody knows if they really can live forever,
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E ninguén sabe se realmente poden vivir para sempre,
15:09
or what keeps them from aging.
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ou qué lles impide envellecer.
15:11
It's not clear.
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Non está claro.
15:13
If you look at birds, which live a long time,
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Se observamos ás aves, que teñen unha vida longa,
15:16
cells from the birds tend to be more resistant
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as súas células tenden a ser máis resistentes
15:19
to a lot of different environmental stresses
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ante varios tipos de estrés ambiental
15:21
like high temperature
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coma as altas temperaturas
15:23
or hydrogen peroxide, things like that.
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ou o peróxido de hidróxeno, cousas así.
15:25
And our long-lived mutants are too.
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E tamén é así cos nosos mutantes lonxevos.
15:27
They're more resistant to these kinds of stresses.
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Son máis resistentes a este tipo de estrés.
15:29
So it could be that the pathways that I've been talking about,
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Así que podería ser que as rutas das que falei,
15:32
which are set to run really quickly in the worm,
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que ocorren realmente rápido nos vermes,
15:35
have a different normal set point
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teñan un punto de inicio normal distinto
15:38
in something like a bird, so that a bird can live a lot longer.
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nas aves,por exemplo, para que as aves vivan mais tempo.
15:41
And maybe they're even set really differently
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E quizais incluso estén determinadas de forma moi distinta
15:43
in animals with no senescence at all -- but we don't know.
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en animais sen senectude; pero non o sabemos.
15:46
MR: But what you're talking about here
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MR: Pero do que estás a falar eiquí
15:48
is not extending human lifespan
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non é de alongar a esperanza de vida
15:51
by preventing death,
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evitando a morte,
15:53
so much as extending human youthspan.
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senón de prolongar a xuventude.
15:55
CK: Yes, that's right.
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CK: Sí, correcto.
15:57
It's more like, say, if you were a dog.
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É coma, digamos, se foras un can.
15:59
You notice that you're getting old, and you look at your human
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Daste conta de que estás envellecendo, e observas o teu humán
16:01
and you think, "Why isn't this human getting old?"
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e pensas, "Por qué non está envellecendo este humán?"
16:03
They're not getting old in the dog's lifespan.
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Non están envellecendo no tempo de vida canino.
16:05
It's more like that.
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Parécese a iso.
16:07
But now we're the human looking out and imagining a different human.
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Agora os humáns miramos e imaxinamos un ser humano diferente.
16:11
MR: Thank you very much indeed, Cynthia Kenyon.
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MR: Moitas grazas de verdade, Cynthia Kenyon.
16:14
(Applause)
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(Aplausos)
ABOUT THE SPEAKER
Cynthia Kenyon - Biochemist, geneticistWhen it comes to aging well, having “good genes” (or rather, mutant ones) is key, says Cynthia Kenyon. She unlocked the genetic secret of longevity in roundworms — and now she’s working to do the same for humans.
Why you should listen
Cynthia Kenyon is revolutionizing our understanding of aging. As an expert in biochemistry and biophysics at the University of California at San Francisco, she is particularly interested in the influence that genetics have on age-related diseases (from cancer to heart failure) in living things.
Her biggest breakthrough was figuring out that there’s a “universal hormonal control for aging”: carbohydrate intake, which can have a dramatic effect on how two critical genes behave, reducing insulin production and boosting repair and renovation activities. So far, her theory has proved true for worms, mice, rats, and monkeys — and she suspects it applies to humans, too.
By studying aging, Kenyon believes that she and other scientists (many of whom have successfully duplicated her experiments) will be able to pinpoint the molecules responsible for the onset of age-related diseases in people and prevent them. She’s co-founded a drug-development company called Elixir Pharmaceuticals to do just that.
She says: "The link between aging and age-related disease suggests an entirely new way to combat many diseases all at once; namely, by going after their greatest risk factor: aging itself."
Cynthia Kenyon | Speaker | TED.com