The science of cells that never get old | Elizabeth Blackburn

翻译人员: Cindy Zheng-Huang 校对人员: Yu Xie

Where does the end begin?

终点是从哪开始的？

Well, for me, it all began with this little fellow.

对我来说，一切都是从 这个小家伙开始。

This adorable organism --

这个可爱的微生物

well, I think it's adorable --

是的，我觉得它很可爱，

is called Tetrahymena and it's a single-celled creature.

它被称为“四膜虫”， 是一种单细胞生物，

它也被称为藻类。

It's also been known as pond scum.

So that's right, my career started with pond scum.

没错，我的职业生涯从浮渣开始

Now, it was no surprise I became a scientist.

我成为一名科学家 并不令人感到意外。

Growing up far away from here,

我在离这里很远的地方长大,

as a little girl I was deadly curious

还是一个小女孩时 就对所有活物

about everything alive.

感到非常的好奇。

I used to pick up lethally poisonous stinging jellyfish and sing to them.

我常常捡起有毒刺的水母 并对它们歌唱。

And so starting my career,

所以，我刚开始职业生涯的时候，

I was deadly curious about fundamental mysteries

就对生命的奥秘非常的好奇

of the most basic building blocks of life,

特别是那些构成生命的最基本要素。

and I was fortunate to live in a society where that curiosity was valued.

幸运的是，我生活在 一个重视这种好奇的社会。

Now, for me, this little pond scum critter Tetrahymena

现在，对我来说，这种小藻类生物“四膜虫”，

was a great way to study the fundamental mystery

是一个研究这个基本奥秘的好方法。

I was most curious about:

我最好奇的是有关：

those bundles of DNA in our cells called chromosomes.

在我们细胞中 称为染色体的那一簇簇DNA。

And it was because I was curious about the very ends of chromosomes,

这是因为我对染色体的最末端，即“端粒"

known as telomeres.

这一部分非常有兴趣。

Now, when I started my quest,

在我开始探索时，

all we knew was that they helped protect the ends of chromosomes.

我们所知道的就是 它们保护染色体的末端。

It was important when cells divide.

这在细胞分裂时很重要

It was really important,

真的特别重要。

but I wanted to find out what telomeres consisted of,

但我想搞清楚端粒由什么组成，

and for that, I needed a lot of them.

为此，我需要许多端粒。

And it so happens that cute little Tetrahymena

而可爱的小四膜虫，

has a lot of short linear chromosomes,

拥有许多小线性染色体。

around 20,000,

大概有两万个，

so lots of telomeres.

因此数量充足。

And I discovered that telomeres consisted of special segments

我发现端粒包含特殊区段

of noncoding DNA right at the very ends of chromosomes.

非编码DNA的就在染色体的最末端。

But here's a problem.

但，这里有个问题。

Now, we all start life as a single cell.

我们的生命都从一个细胞开始，

It multiples to two. Two becomes four. Four becomes eight,

之后，它倍增成两个， 二个变成成四个，四个变成八个，

and on and on to form the 200 million billion cells

不断分化形成 200万兆个细胞，

that make up our adult body.

组成我们成熟的身体。

And some of those cells have to divide thousands of times.

而且一些细胞 必须分化几千次。

In fact, even as I stand here before you,

事实上，即使我站在你面前，

all throughout my body, cells are furiously replenishing

全身细胞正在疯狂地更新，

to, well, keep me standing here before you.

为了让我能站在你面前。

So every time a cell divides, all of its DNA has to be copied,

每次细胞分裂， 所有的DNA都必须被复制，

all of the coding DNA inside of those chromosomes,

所有在那些染色体内部的DNA编码，

because that carries the vital operating instructions

因为它们携带了重要的操作指南，

that keep our cells in good working order,

使我们的细胞保持良好的工作状态。

so my heart cells can keep a steady beat,

这样我的心脏细胞就可以 保持稳定的跳动。

which I assure you they're not doing right now,

但事实上，我向各位保证 它们现在并没有做到。

and my immune cells

而我的免疫细胞，

can fight off bacteria and viruses,

能抵抗细菌和病毒，

and our brain cells can save the memory of our first kiss

还有我们的脑细胞 可以保存我们初吻的记忆，

and keep on learning throughout life.

并且保持终身学习。

But there is a glitch in the way DNA is copied.

但在DNA复制的过程总会有个小故障

It is just one of those facts of life.

当然，这只是生活中的事实之一。

Every time the cell divides and the DNA is copied,

每次细胞分裂 DNA被复制，

some of that DNA from the ends gets worn down and shortened,

一些来自末端的DNA 磨损和缩短，

some of that telomere DNA.

一些DNA端粒。

And think about it

再想一想，

like the protective caps at the ends of your shoelace.

就像在你鞋带的末端保护帽一样

And those keep the shoelace, or the chromosome, from fraying,

那些阻止鞋带， 或染色体磨损的东西

and when that tip gets too short, it falls off,

当那些保护措施变得太短，它就会脱落。

and that worn down telomere sends a signal to the cells.

而那些磨损的端粒则 向细胞发送信号，

"The DNA is no longer being protected."

“这一条DNA不再受到保护了。”

It sends a signal. Time to die.

它发出一个信号，死亡的时刻到了。

So, end of story.

所以，故事的结局。

Well, sorry, not so fast.

哦，对不起，没那么快。

It can't be the end of the story,

这不可能是故事的结局，

because life hasn't died off the face of the earth.

因为生命还没从 地球表面消逝。

So I was curious:

所以我很好奇：

if such wear and tear is inevitable,

如果这样的磨损是不可避免的，

how on earth does Mother Nature make sure

大自然究竟是怎么确保

we can keep our chromosomes intact?

我们可以保持染色体完整呢？

Now, remember that little pond scum critter Tetrahymena?

现在，还记得 池塘里的小四膜虫？

The craziest thing was, Tetrahymena cells never got old and died.

最古怪的是， 四膜虫的细胞从不变老和死亡。

Their telomeres weren't shortening as time marched on.

它们的端粒并没有 随着时间向前而缩短，

Sometimes they even got longer.

有时甚至长得更长。

Something else was at work,

还有别的东西在起作用，

and believe me, that something was not in any textbook.

相信我，那些东西 不在任何教科书中。

So working in my lab with my extraordinary student Carol Greider --

所以，在实验室里我与 我杰出的学生卡罗尔·格雷德一起工作

and Carol and I shared the Nobel Prize for this work --

凯罗尔和我因这项工作 共享了诺贝尔奖。

we began running experiments

我们开始做实验，

and we discovered cells do have something else.

我们发现细胞 确实有其他的东西。

It was a previously undreamed-of enzyme

这是一个以前做梦也想不到的酶。

that could replenish, make longer, telomeres,

它可以补充， 使端粒变得更长。

and we named it telomerase.

我们把它命名为端粒酶。

And when we removed our pond scum's telomerase,

当我们去除掉实验藻的端粒酶，

their telomeres ran down and they died.

它们的端粒水平下降了，死了。

So it was thanks to their plentiful telomerase

所以这得感谢充足的端粒酶

that our pond scum critters never got old.

我们的藻生物从不变老。

OK, now, that's an incredibly hopeful message

因而，从这个实验中 我们可以得出这样一个充满希望的信息，

for us humans to be receiving from pond scum,

从这些藻类生物中得出的。

because it turns out

因为结果就是，

that as we humans age, our telomeres do shorten,

当我们人类衰老， 我们的端粒就随之缩短。

and remarkably, that shortening is aging us.

显然这种缩短 正在使我们衰老。

Generally speaking, the longer your telomeres,

一般来说你的端粒越长，

the better off you are.

你的身体狀況就会越好。

It's the overshortening of telomeres

正是这端粒的过度缩短

that leads us to feel and see signs of aging.

让我们感觉和看到衰老的迹象。

My skin cells start to die

我的皮肤细胞开始死亡，

and I start to see fine lines, wrinkles.

于是我开始看到细纹，皱纹。

Hair pigment cells die.

毛发色素细胞死亡，

You start to see gray.

你就会开始看到这些灰色的头发。

Immune system cells die.

免疫系统细胞死亡，

You increase your risks of getting sick.

你增加了生病的风险。

In fact, the cumulative research from the last 20 years

事实上，20年来持续的研究都

has made clear that telomere attrition

明确表明端粒损耗，

is contributing to our risks of getting cardiovascular diseases,

增加了我们患心血管疾病，

Alzheimer's, some cancers and diabetes,

老年痴呆症，某些癌症和糖尿病的风险。

the very conditions many of us die of.

这些都是现代大多数人的死亡原因。

And so we have to think about this.

所以我们必须考虑这个问题

What is going on?

到底是怎么回事？

This attrition,

这种损耗，

we look and we feel older, yeah.

使我们看起来以及感觉老了。

Our telomeres are losing the war of attrition faster.

我们的端粒正在加快消失。

And those of us who feel youthful longer,

还有那些我们觉得青春更长的人，

it turns out our telomeres are staying longer

结果是我们的端粒保持时间长些，

for longer periods of time,

更长的时间，

extending our feelings of youthfulness

而正是这种延长 也延长了我们的青春感，

and reducing the risks of all we most dread

减少了当我们每渡过一次生日，

as the birthdays go by.

所感到的那种时间流逝的恐惧。

OK,

好的，

seems like a no-brainer.

这么一说好像很简单。

Now, if my telomeres are connected

现在，如果我的端粒水平与

我对变老的感受和我的衰老相关联

to how quickly I'm going to feel and get old,

if my telomeres can be renewed by my telomerase,

如果我的端粒可以 被我的端粒酶更新，

then all I have to do to reverse the signs and symptoms of aging

那么为了扭转衰老的征兆和症状 我做的就是

is figure out where to buy that Costco-sized bottle

弄清楚在哪里能买到 像Costco瓶子那样大小的

of grade A organic fair trade telomerase, right?

A级有机公平交易的端粒酶，对吗？

Great! Problem solved.

太好了，问题解决了.

(Applause)

（掌声）

Not so fast, I'm sorry.

但实际上并没有这么快，我很抱歉

Alas, that's not the case.

唉，事实并非如此。

OK. And why?

为什么呢？

It's because human genetics has taught us

这因为人类遗传学已经告诉我们，

that when it comes to our telomerase,

当涉及到我们的端粒酶时，

we humans live on a knife edge.

我们人类生活在刀刃上，

OK, simply put,

好吧，简单地说，

yes, nudging up telomerase does decrease the risks of some diseases,

是的，提高端粒酶的水平 确实减少某些疾病的风险，

but it also increases the risks of certain and rather nasty cancers.

但它也增加了某些恶性肿瘤的风险。

So even if you could buy that Costco-sized bottle of telomerase,

所以即使你能买到 Costco样大瓶的端粒酶，

and there are many websites marketing such dubious products,

而且有很多网站， 销售这种可疑产品。

the problem is you could nudge up your risks of cancers.

但这么做的弊端就是 你可能提高了患癌症的风险。

And we don't want that.

我们并不想要那样。

Now, don't worry,

现在，别担心

and because, while I think it's kind of funny that right now,

因为，虽然我觉得有点好笑，

you know, many of us may be thinking, "Well, I'd rather be like pond scum," ...

现在我们很多人可能在想， 好吧，我宁愿是池塘里的水藻。

(Laughter)

（笑声）

there is something for us humans

人类机体内

in the story of telomeres and their maintenance.

就存在着端粒维护机制。

But I want to get one thing clear.

但是我想澄清一件事，

It isn't about enormously extending human lifespan

这并不是关于 延长人类的寿命

or immortality.

或使人类达成永生的机制。

It's about health span.

这是关于健康的寿命,

Now, health span is the number of years of your life

健康寿命是指你生命中有多少年

when you're free of disease, you're healthy, you're productive,

你没有疾病，你很健康，很有生产力，

you're zestfully enjoying life.

你兴致勃勃地享受生活。

Disease span, the opposite of health span,

带病生存与健康寿命相反

is the time of your life spent feeling old and sick and dying.

是你生命中感觉衰老，生病和死亡的时刻。

So the real question becomes,

所以问题实际就变成

OK, if I can't guzzle telomerase,

好吧，如果我不能狂饮端粒酶饮料

do I have control over my telomeres' length

我们是否能控制 自己端粒的长度。

and hence my well-being, my health,

因此我的良好状态，我的健康，

without those downsides of cancer risks?

就不会有这些负面癌症影响的风险？

OK?

可以吗?

So, it's the year 2000.

所以，这是2000年

Now, I've been minutely scrutinizing little teeny tiny telomeres

现在，我已经详细检查 那小小的，极小的，极微的的端粒

very happily for many years,

快乐地过了很多年，

when into my lab walks a psychologist named Elissa Epel.

一个叫伊丽莎 埃佩尔的心理学家 走进我的实验室，

Now, Elissa's expertise is in the effects of severe, chronic psychological stress

现在，伊丽莎专长的是 严重慢性心理压力，

on our mind's and our body's health.

于身心健康的影响.

And there she was standing in my lab,

她站在我的实验室里，

which ironically overlooked the entrance to a mortuary, and --

讽刺的是从那可以看到太平间入口，

(Laughter)

（笑声）

And she had a life-and-death question for me.

她有一个关生有死的问题问我

"What happens to telomeres in people who are chronically stressed?"

“在那些长期处于压力的人群中, 端粒会发生什么变化？”

she asked me.

她问我。

You see, she'd been studying caregivers,

你看，她一直在研究照护者，

and specifically mothers of children with a chronic condition,

特别是慢性病儿童的母亲

be it gut disorder, be it autism, you name it --

无论是肠道紊乱，自闭症， 凡你说得出的都有 ---

a group obviously under enormous and prolonged psychological stress.

这个群体显然是长期 处于巨大心理压力之下。

I have to say, her question

我不得不说，她的问题

changed me profoundly.

深深地改变了我。

See, all this time I had been thinking of telomeres

你看，长期以来， 我一直在思考端粒

as those miniscule molecular structures that they are,

那些微小的分子结构，

and the genes that control telomeres.

和那控制端粒的基因。

And when Elissa asked me about studying caregivers,

当伊丽莎问我 有关照护者的研究。

I suddenly saw telomeres in a whole new light.

我突然看到端粒， 在崭新的亮点之中。

I saw beyond the genes and the chromosomes

我看到了超越基因和染色体之外，

into the lives of the real people we were studying.

进入到我们所研究的人 真实的生活之中，

And I'm a mom myself,

我自己也是个妈妈

and at that moment,

在那一刻，

I was struck by the image of these women

我被这些女人的形象所触动。

dealing with a child with a condition

照顾一个有病的孩子，

very difficult to deal with, often without help.

很难处理， 常常没有帮助

And such women, simply,

而这样的女人，显然，

often look worn down.

经常看起来疲惫不堪。

So was it possible their telomeres were worn down as well?

那么她们的端粒 会不会也损耗了呢？

So our collective curiosity went into overdrive.

所以，我们的所有的好奇心 马上超速运转。

Elissa selected for our first study a group of such caregiving mothers,

伊丽莎为我们第一个研究 选了一组这样的照护妈妈。

and we wanted to ask: What's the length of their telomeres

我们想要问： 端粒的长度

compared with the number of years that they have been caregiving

与她们照顾慢性病孩子的年数相比.

for their child with a chronic condition?

So four years go by

四年过去了，

and the day comes when all the results are in,

在所有的结果都来临这一天，

and Elissa looked down at our first scatterplot

伊丽莎看着 我们的第一个散点图，

and literally gasped,

简直深吸了一口气，

because there was a pattern to the data,

因为数据呈现一个模式，

and it was the exact gradient that we most feared might exist.

正是我们最害怕 可能存在的梯度变化。

It was right there on the page.

就呈现在那页上。

The longer, the more years that is,

时间越长，年数越多，

the mother had been in this caregiving situation,

母亲处于 在这照顾者的情况下，

no matter her age,

不管她的年龄的大小，

the shorter were her telomeres.

她的端粒越短。

And the more she perceived

和她越感到

her situation as being more stressful,

她的处境压力越大

the lower was her telomerase and the shorter were her telomeres.

她的端粒酶越低， 她的端粒越短。

So we had discovered something unheard of:

所以我们发现了一些前所未闻的东西：

the more chronic stress you are under, the shorter your telomeres,

你承受的慢性压力越大， 你的端粒越短，

meaning the more likely you were to fall victim to an early disease span

意味着你越有可能 过早患病

and perhaps untimely death.

也许是英年早逝。

Our findings meant that people's life events

我们的研究结果意味着 人们的生活事件，

and the way we respond to these events

以及我们对这些事件的反应方式

can change how you maintain your telomeres.

可以改变 你如何维持你的端粒。

So telomere length wasn't just a matter of age counted in years.

端粒长度并不只是年岁长短，

Elissa's question to me,

伊丽莎的问题于我而言，

back when she first came to my lab, indeed had been a life-and-death question.

就在她第一次来到我的实验室时， 的确是一个生死问题。

Now, luckily, hidden in that data there was hope.

现在，幸运的是 隐藏在这些数据中有希望。

We noticed that some mothers,

我们注意到一些母亲，

despite having been carefully caring for their children for many years,

尽管细心照顾 她们的孩子多年，

had been able to maintain their telomeres.

却能够维持她们的端粒。

So studying these women closely revealed that they were resilient to stress.

所以仔细研究这些女人 她们能承受压力。

Somehow they were able to experience their circumstances

不知何故她们能 经历她们的处境，

not as a threat day in and day out

不当作一日复一日的威胁

but as a challenge,

而是作为挑战。

and this has led to a very important insight for all of us:

这给了我们所有人一个领悟：

we have control over the way we age

我们可以控制自己的老化过程。

all the way down into our cells.

一直深入到我们的细胞。

OK, now our initial curiosity became infectious.

好了，现在我们起初的好奇 变得有传染性。

Thousands of scientists from different fields

成千上万的科学家 从不同的领域

added their expertise to telomere research,

加入他们的专业知识在 端粒的研究上，

and the findings have poured in.

研究结果也大量涌现。

It's up to over 10,000 scientific papers and counting.

超过10，000篇 科技论文与统计。

So several studies rapidly confirmed our initial finding

所以，有一些研究 很快证实了我们的初步发现。

that yes, chronic stress is bad for telomeres.

是的，慢性应激 对端粒不好。

And now many are revealing

现在许多研究揭示，

that we have more control over this particular aging process

我们在这种老化过程 有更多的掌控权，

than any of us could ever have imagined.

比我们所能想象的更多。

A few examples:

举几个例子：

a study from the University of California, Los Angeles

加利福尼亚洛杉矶大学的一项研究，

of people who are caring for a relative with dementia, long-term,

长期照顾患有痴呆症亲人，

and looked at their caregiver's telomere maintenance capacity

研究他们的照顾者 端粒的维持能力，

and found that it was improved

发现它得到了改善，

by them practicing a form of meditation

通过练习一种冥想，

for as little as 12 minutes a day for two months.

只需每天12分钟持续两个月。

Attitude matters.

态度很重要。

If you're habitually a negative thinker,

如果你习惯了消极的思考，

you typically see a stressful situation with a threat stress response,

你通常遇到压力情形 会以威胁应激作反应，

meaning if your boss wants to see you,

比如，你的老板想见你，

you automatically think, "I'm about to be fired,"

你自然而然地想， “我就要被解雇了，”

and your blood vessels constrict,

你的血管收缩，

and your level of the stress hormone cortisol creeps up,

和你的压力荷尔蒙 皮质醇水平升高，

and then it stays up,

而且持续在那，

and over time, that persistently high level of the cortisol

随着时间的推移， 这种持续高水平的皮质醇

actually damps down your telomerase.

实际上，抑制你的端粒酶，

Not good for your telomeres.

不利于你的端粒。

On the other hand,

另一方面，

if you typically see something stressful as a challenge to be tackled,

如果你通常视有压力的事情， 作为一个有待解决的挑战，

then blood flows to your heart and to your brain,

于是，血液流向你的心脏。 和你的大脑，

and you experience a brief but energizing spike of cortisol.

你经历了一个简短的 但兴奋的皮质醇峰值。

And thanks to that habitual "bring it on" attitude,

感谢那个 “来吧”的态度，

your telomeres do just fine.

你的端粒会没事，

So ...

所以,

What is all of this telling us?

这一切告诉我们什么？

Your telomeres do just fine.

你的端粒很好。

You really do have power to change what is happening

你真的有权力 改变正在发生的事情

to your own telomeres.

对你自己的端粒。

But our curiosity just got more and more intense,

但我们的好奇心 变得越来越強烈，

because we started to wonder,

因为我们开始想知道，

what about factors outside our own skin?

我们自己皮肤以外的因素呢？

Could they impact our telomere maintenance as well?

它们也能影响 我们的端粒维持吗？

You know, we humans are intensely social beings.

你知道，我们人类 是极度的群居动物

Was it even possible that our telomeres were social as well?

我们的端粒也可能是有社会性的吗？

And the results have been startling.

结果令人吃惊。

As early as childhood,

早在童年时代，

emotional neglect, exposure to violence,

情感上的忽视、暴露在暴力之中，

bullying and racism

欺凌和种族主义

all impact your telomeres, and the effects are long-term.

都会影响你的端粒， 其影响是长期的。

Can you imagine the impact on children

你能想象对孩子的影响,

of living years in a war zone?

在战区度过多年，

People who can't trust their neighbors

人们不能信任邻居,

and who don't feel safe in their neighborhoods

在他们的社区觉得不安全,

consistently have shorter telomeres.

端粒长度较短。

So your home address matters for telomeres as well.

所以你的家庭住址 对端粒也很重要。

On the flip side,

反过来，

tight-knit communities, being in a marriage long-term,

紧密结合的社区， 长久的婚姻，

and lifelong friendships, even,

甚至终身的友谊，

all improve telomere maintenance.

改善端粒的维持。

So what is all this telling us?

那么这一切告诉我们什么？

It's telling us that I have the power to impact my own telomeres,

它告诉我们，我有力量 影响我自己的端粒，

and I also have the power to impact yours.

我也有能力影响你的。

Telomere science has told us just how interconnected we all are.

端粒科学告诉我们 我们是那么的连接在一起。

But I'm still curious.

但我还是很好奇。

I do wonder

我真的想知到，

what legacy all of us

我们所有人

will leave for the next generation?

将遗留给下一代什么？

Will we invest

我们是否会投资

in the next young woman or man

在下一个年轻男女，

peering through a microscope at the next little critter,

透过显微镜窥视 下一个小动物，

the next bit of pond scum,

下一堆绿藻，

curious about a question we don't even know today is a question?

对某个问题很好奇 我们今天都不知道是个问题？

It could be a great question that could impact all the world.

这可能是个很好的 会影响整个世界的问题.

And maybe, maybe you're curious about you.

也许，也许你对自己很好奇。

Now that you know how to protect your telomeres,

现在你知道了 如何保护你的端粒，

are you curious what are you going to do

你好奇你将要做什么吗？

with all those decades of brimming good health?

在身体健康的几十年。

And now that you know you could impact the telomeres of others,

现在你知道你可以影响 其他人的端粒，

are you curious

你是否好奇

how will you make a difference?

你将如何改变世界？

And now that you know the power of curiosity to change the world,

现在你知道了 好奇心改变世界的力量，

how will you make sure that the world invests in curiosity

你将如何确定 世界投资于好奇心

for the sake of the generations that will come after us?

为了下一代，为了来人？

Thank you.

谢谢。

(Applause)

（掌声）