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So how can a hormone ultimately affect the rate of aging?
那么，激素到底是怎样影响衰老的速度呢？
How could that work?
原理是什么呢？
Well it turns out that in the daf-2 mutants,
原来在daf-2变异体中
a whole lot of genes are switched on in the DNA
有大量的基因被转变到DNA里面
that encode proteins that protect the cells and the tissues,
蛋白质编码保护细胞和组织
and repair damage.
和修复损坏基因的功能
And the way that they're switched on
同时基因被转变的途径
is by a gene regulator protein called FOXO.
是被一个基因调节器的蛋白质叫FOXO
So in a daf-2 mutant --
所以在daf 2的变异体中
you see that I have the X drawn here through the receptor.
你可以看到这个X型绘制图的受体
The receptor isn't working as well.
这个受体也运转得不怎么好
Under those conditions, the FOXO protein in blue
在这些条件下，蓝颜色的FOXO蛋白质
has gone into the nucleus --
已经转移到核心里面了
that little compartment there in the middle of the cell --
这个小小的隔室在细胞的最中间
and it's sitting down on a gene binding to it.
同时也坐落在基因的粘合物上
You see one gene. There are lots of genes actually that bind on FOXO.
你看到一个基因。这里有大量的基因实际上捆绑在FOXO上
And it's just sitting on one of them.
并且坐落在它们其中的一个上面
So FOXO turns on a lot of genes.
所以FOXO开启着大量的基因
And the genes it turns on includes antioxidant genes,
同时这些基因也开启着抗氧化的基因
genes I call carrot-giver genes,
这些基因我称呼它为胡萝卜者基因
whose protein products
这些蛋白质产物
actually help other proteins to function well --
实际上帮助其他的蛋白质的机能运转顺畅
to fold correctly and function correctly.
同时也帮助蛋白质融合和运转准确
And it can also escort them to the garbage cans of the cell
同时也给它们护航到细胞中的垃圾场
and recycle them if they're damaged.
并且回收被损坏的蛋白质
DNA repair genes
DNA修复基因
are more active in these animals.
在这些动物身上更活跃
And the immune system is more active.
免疫系统也更活跃
And many of these different genes, we've shown,
我们展示的许多这些不同基因
actually contribute to the long lifespan of the daf-2 mutant.
实际上都作用于daf 2变异体的延长寿命
So it's really interesting.
所以这是很有趣的
These animals have within them
带有这些基因的动物
the latent capacity to live much longer than they normally do.
比起普通的有活得更久的潜力
They have the ability
它们有能力
to protect themselves from many kinds of damage,
保护自身免于很多的伤害
which we think makes them live longer.
我们认为这使得它们活得更长
So what about the normal worm?
那关于正常线虫呢
Well when the daf-2 receptor is active,
当daf-2受体是活跃的
then it triggers a series of events
它引发了一系列
that prevent FOXO
来阻止FOXO
from getting into the nucleus where the DNA is.
进入到DNA所处的中心
So it can't turn the genes on.
所以基因不能激活
That's how it works. That's why we don't see the long lifespan,
这就是运作的方式。也就是我们看不到延长寿命的原因
until we have the daf-2 mutant.
除非有daf 2变异体
But what good is this for the worm?
但对线虫来说有什么好处吗
Well we think that insulin and IGF-1 hormones
胰岛素和IGF-1激素
are hormones that are particularly active
是特别活跃
under favorable conditions -- in the good times --
在有利条件下--好的时机下--
when food is plentiful and there's not a lot of stress in the environment.
当食物是充足的，没有很多压力的环境下
Then they promote the uptake of nutrients.
然后它们促使营养品的产生
You can store the food, use it for energy,
可以储存食物，用它来补能量
grow, etc.
成长等
But what we think is that, under conditions of stress,
但我们认为在压力条件下
the levels of these hormones drop --
这些激素水平会下降
for example, having limited food supply.
例如在有限的食物供给时
And that, we think,
我们认为那
is registered by the animal as a danger signal,
对于动物而言是个危险信号
a signal that things are not okay
预示什么不对头
and that it should roll out its protective capacity.
它们的保护功能就开启了
So it activates FOXO, FOXO goes to the DNA,
所以它激活了FOXO，FOXO进入DNA
and that triggers the expression of these genes
引发这些基因显现
that improves the ability of the cell
来带动细胞能力
to protect itself and repair itself.
从而保护和修复自身
And that's why we think the animals live longer.
这是我们认为动物活长久的原因
So you can think of FOXO
你可以想象FOXO
as being like a building superintendent.
为一个大楼的看门人
So maybe he's a little bit lazy,
或许他有点懒
but he's there, he's taking care of the building.
但他在那儿掌管着大楼
But it's deteriorating.
但这是不好的
And then suddenly, he learns that there's going to be a hurricane.
突然，他了解到将有一场飓风
So he doesn't actually do anything himself.
所以他自己实际不做任何事
He gets on the telephone --
但他打起电话--
just like FOXO gets on the DNA --
就像FOXO进入到DNA--
and he calls up
他打电话给
the roofer, the window person,
修屋顶的人，修窗户的人
the painter, the floor person.
油漆工，修地板的人
And they all come and they fortify the house.
他们都来了，加固了房屋。
And then the hurricane comes through,
然后飓风穿过
and the house is in much better condition than it would normally have been in.
房屋比起它原本的要更加稳固
And not only that, it can also just last longer,
不但如此，它也可以很久矗立不倒
even if there isn't a hurricane.
甚至不是飓风来临
So that's the concept here
所以这的概念
for how we think this life extension ability exists.
就类似我们认为生命延长力的发生情形
Now the really cool thing about FOXO
关于FOXO真正有趣的
is that there are different forms of it.
是有不同种的FOXO
We all have FOXO genes,
我们大家都有FOXO基因
but we don't all have exactly the same form of the FOXO gene.
但我们不是完全拥有同一种FOXO基因
Just like we all have eyes,
如同我们都有眼睛
but some of us have blue eyes and some of us have brown eyes.
但有些人是蓝色的眼睛，有些是棕色的
