The science of cells that never get old | Elizabeth Blackburn

譯者: Lilian Chiu 審譯者: Helen Chang

Where does the end begin?

結束是從何開始的？

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

對我來說，它開始於這個小傢伙。

This adorable organism --

這可愛的有機體，

well, I think it's adorable --

我認為它很可愛，

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

它叫做四膜蟲，是種單細胞生物。

It's also been known as pond scum.

它也就是池塘浮渣。

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

是的，我的職涯始於池塘浮渣。

Now, it was no surprise I became a scientist.

我變成科學家並不讓人意外。

Growing up far away from here,

我在離這裡很遠的地方長大，

as a little girl I was deadly curious

我小時候非常有好奇心，

about everything alive.

對所有的生物都好奇。

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

我以前會撿起有致命劇毒 會螫人的水母，然後對牠們唱歌。

And so starting my career,

所以，開始我的職涯時，

I was deadly curious about fundamental mysteries

我非常好奇，想解開最根本的謎題，

of the most basic building blocks of life,

想知道構成生命的基礎積木是什麼，

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

很幸運，我所在的社會 很重視好奇心。

Now, for me, this little pond scum critter Tetrahymena

對我而言，四膜蟲 這池塘浮渣小生物

was a great way to study the fundamental mystery

是研究我最好奇的 根本謎題的好方式：

I was most curious about:

those bundles of DNA in our cells called chromosomes.

我們的細胞內大量的 DNA，

也就是所謂的染色體。

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

因為我對染色體的末端很好奇，

known as telomeres.

也就是所謂的端粒。

Now, when I started my quest,

當我開始探索，

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

我們只知道：它們 協助保護染色體的末端。

It was important when cells divide.

細胞分裂時，這點很重要。

It was really important,

它相當重要，

but I wanted to find out what telomeres consisted of,

但我想要了解端粒是什麼組成的，

and for that, I needed a lot of them.

為這個目的，我需要很多端粒。

And it so happens that cute little Tetrahymena

剛好這個可愛的小四膜蟲

has a lot of short linear chromosomes,

有很多短短線性的染色體。

around 20,000,

大約兩萬個，

so lots of telomeres.

所以會有很多端粒。

And I discovered that telomeres consisted of special segments

我發現端粒包括

位在染色體最末端 未編碼的特殊 DNA 區段。

of noncoding DNA right at the very ends of chromosomes.

But here's a problem.

但，有一個問題。

Now, we all start life as a single cell.

生命是從單細胞開始的。

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

一個會變成兩個， 兩個變成四個，四個變成八個，

and on and on to form the 200 million billion cells

一路這樣下去， 形成了二十萬兆個細胞，

that make up our adult body.

組成了成人的身體。

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

有些細胞需要分裂數千次。

In fact, even as I stand here before you,

事實上，即使我站在各位面前，

all throughout my body, cells are furiously replenishing

我整個身體的細胞正瘋狂地補充，

to, well, keep me standing here before you.

讓我能夠持續站在你們面前。

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

每當一個細胞分裂， 它所有的 DNA 都會被複製，

all of the coding DNA inside of those chromosomes,

那些染色體中所有編碼的 DNA，

because that carries the vital operating instructions

因為那帶有極重要的運作指示，

that keep our cells in good working order,

讓我們的細胞 能處於良好的工作狀態，

so my heart cells can keep a steady beat,

這麼一來我的心臟細胞 才能保持穩定的心跳，

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

我向各位保證，它們現在並沒做到，

and my immune cells

而我的免疫細胞，

can fight off bacteria and viruses,

能擊退細菌和病毒，

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

我們的頭腦細胞 能儲存我們初吻的記憶，

and keep on learning throughout life.

並在整個人生中持續學習。

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

但複製 DNA 的方式有個小毛病，

It is just one of those facts of life.

僅是生命的事實之一。

Every time the cell divides and the DNA is copied,

每當細胞分裂、DNA 被複製，

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

某些末端 DNA 會磨損縮短，

some of that telomere DNA.

一些端粒的 DNA。

And think about it

可以用這方式來想：

like the protective caps at the ends of your shoelace.

就像你的鞋帶末端的保護套。

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

它們能讓鞋帶或染色體不會被磨損，

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

當尖端變得太短時，它就會脫落，

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

而那被磨損掉的端粒 就會發送一個訊號給細胞。

"The DNA is no longer being protected."

「這 DNA 不再受到保護。」

It sends a signal. Time to die.

它發出訊號。是死亡的時候了。

So, end of story.

所以，故事結束。

Well, sorry, not so fast.

抱歉，沒那麼快。

It can't be the end of the story,

故事不可能這樣結束，

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

因為生命還沒從地球表面上消逝。

So I was curious:

所以我很好奇：

if such wear and tear is inevitable,

如果這種損耗是無可避免的，

how on earth does Mother Nature make sure

大自然到底要如何確保

我們能保持不讓染色體受損？

we can keep our chromosomes intact?

Now, remember that little pond scum critter Tetrahymena?

還記得那池塘浮渣小生物四膜蟲嗎？

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

最瘋狂的是，四膜蟲細胞 從來不會變老或死亡。

Their telomeres weren't shortening as time marched on.

牠們的端粒並不會隨時間而變短。

Sometimes they even got longer.

有時甚至還會變長。

Something else was at work,

還有某樣東西在運作，

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

相信我，那某樣東西 並不在任何教科書中。

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

所以，我和傑出學生 凱洛葛萊德在實驗室中合作──

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

凱洛和我共享 這項研究贏得的諾貝爾獎──

we began running experiments

我們開始進行實驗，

and we discovered cells do have something else.

我們發現細胞的確有其他的東西。

It was a previously undreamed-of enzyme

是先前意想不到的酶（酵素），

that could replenish, make longer, telomeres,

它能補充端粒，讓端粒更長，

and we named it telomerase.

我們將它命名為「端粒酶」。

And when we removed our pond scum's telomerase,

當我們移除池塘浮渣的端粒酶後，

their telomeres ran down and they died.

牠們的端粒就會耗盡而死亡。

So it was thanks to their plentiful telomerase

所以要歸功於豐富的端粒酶，

that our pond scum critters never got old.

我們的池塘浮渣才能永生不老。

OK, now, that's an incredibly hopeful message

那是我們人類能從池塘浮渣身上

for us humans to be receiving from pond scum,

得到的一個非常有希望的訊息，

because it turns out

因為結果發現，

that as we humans age, our telomeres do shorten,

隨著我們人類年紀增長， 我們的端粒確實會變短，

and remarkably, that shortening is aging us.

很驚人的是， 那縮短現象讓我們變老。

Generally speaking, the longer your telomeres,

一般來說，你的端粒越長，

the better off you are.

你的狀況就會越好。

It's the overshortening of telomeres

是端粒過度減短的現象

that leads us to feel and see signs of aging.

導致我們會感到及看到老化的徵象。

My skin cells start to die

我的皮膚細胞開始死亡，

and I start to see fine lines, wrinkles.

我就會開始看到線條、皺紋。

Hair pigment cells die.

頭髮色素細胞死亡，

You start to see gray.

你就會開始看到白髮。

Immune system cells die.

免疫細胞死亡，

You increase your risks of getting sick.

你被攻擊的風險就會提升。

In fact, the cumulative research from the last 20 years

事實上，過去二十年所累積的研究

has made clear that telomere attrition

清楚地指出，

端粒損耗可能造成罹患

is contributing to our risks of getting cardiovascular diseases,

像是：心血管疾病、阿滋海默症、

Alzheimer's, some cancers and diabetes,

某些癌症，以及糖尿病等 許多致死疾病的風險。

the very conditions many of us die of.

And so we have to think about this.

所以我們得要想想這一點。

What is going on?

發生了什麼事？

This attrition,

這種損耗，

we look and we feel older, yeah.

我們看起來且感覺起來變老了。

Our telomeres are losing the war of attrition faster.

我們的端粒在 損耗之戰中敗退得很快。

And those of us who feel youthful longer,

至於覺得年輕時間比較長的人，

it turns out our telomeres are staying longer

結果發現是端粒能留比較久，

for longer periods of time,

比較長的時間，

extending our feelings of youthfulness

延長我們對於年輕的感覺，

and reducing the risks of all we most dread

並減少我們隨著每個生日過去

as the birthdays go by.

而最害怕的那些風險。

OK,

好。

seems like a no-brainer.

似乎很簡單。

Now, if my telomeres are connected

如果我的端粒和我多快感到變老

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

及實際變老是有關聯的，

if my telomeres can be renewed by my telomerase,

如果我能用端粒酶來復原端粒，

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

那麼若我想要反轉 老化的徵兆和症狀，

is figure out where to buy that Costco-sized bottle

就是要找個地方 買像好市多那樣超大罐、

of grade A organic fair trade telomerase, right?

A 級、有機、公平貿易的 端粒酶，對吧？

Great! Problem solved.

好極了！問題解決。

(Applause)

（掌聲）

Not so fast, I'm sorry.

很抱歉，沒那麼快。

Alas, that's not the case.

唉，並不是那樣的。

OK. And why?

那為什麼呢？

It's because human genetics has taught us

因為人類遺傳學教導我們，

that when it comes to our telomerase,

談到我們的端粒酶時，

we humans live on a knife edge.

我們人類是住在刀緣上的。

OK, simply put,

簡單來說，

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

是的，增加端粒酶的確 可以減少一些疾病的風險，

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

但同時也會增加某些 很糟糕的癌症的風險。

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

所以，就算你能買到 像好市多那樣超大罐的端粒酶，

and there are many websites marketing such dubious products,

有許多網站在行銷這類可疑的產品，

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

問題是你有可能增加罹癌的風險。

And we don't want that.

我們不想要那樣。

Now, don't worry,

別擔心，

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

因為，雖然我覺得有點好笑，

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

也許此刻很多人正想著， 我寧可像池塘浮渣一樣。

(Laughter)

（笑聲）

there is something for us humans

在這關於端粒以及維護端粒的真相中

in the story of telomeres and their maintenance.

還是有我們人類可以學習之處。

But I want to get one thing clear.

但我想先澄清一件事。

It isn't about enormously extending human lifespan

重點並不是將人類壽命期間延長很多

or immortality.

或是永生不死。

It's about health span.

重點是「健康期間」。

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

健康期間，就是你人生中有多少年

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

是沒有疾病、很健康、有生產力、

you're zestfully enjoying life.

能夠熱情享受人生的。

Disease span, the opposite of health span,

相對於健康期間的「疾病期間」，

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

指的就是你人生中有多長時間 覺得自己老、病、和垂死。

So the real question becomes,

所以，真正的問題變成是，

OK, if I can't guzzle telomerase,

如果我無法狂飲端粒酶，

do I have control over my telomeres' length

我是否能控制端粒酶的長度，

and hence my well-being, my health,

進而控制我的福祉、我的健康，

without those downsides of cancer risks?

而沒有癌症風險的壞處？

OK?

好嗎？

So, it's the year 2000.

所以，那是 2000 年。

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

多年來，我很快樂地、分分鐘鐘地

持續仔細觀察著那些極微小的端粒，

very happily for many years,

when into my lab walks a psychologist named Elissa Epel.

直到有一天，名叫伊莉莎埃佩爾的 心理學家走入了我的實驗室。

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

伊莉莎的專長在於嚴重慢性心理壓力

對於我們身、心健康的影響。

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

And there she was standing in my lab,

她出現在我的實驗室，

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

很諷刺的是從實驗室 可以眺望停屍間的入口，而且──

(Laughter)

（笑聲）

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

她有個生死問題要問我。

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

「有慢性壓力的人， 他們的端粒會發生什麼事？」

she asked me.

她這樣問我。

You see, she'd been studying caregivers,

她一直在研究照護者，

and specifically mothers of children with a chronic condition,

特別慢性病孩童的母親，

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

可能是腸病，可能是自閉症， 任何你想得到的──

a group obviously under enormous and prolonged psychological stress.

這個族群很顯然處在 巨大且長期的心理壓力之下。

I have to say, her question

我不得不說，

她的問題深深改變了我。

changed me profoundly.

See, all this time I had been thinking of telomeres

一直以來，

我從小分子結構的角度來思考端粒

as those miniscule molecular structures that they are,

and the genes that control telomeres.

和控制端粒的基因。

And when Elissa asked me about studying caregivers,

當伊莉莎問我 關於照護者的問題時，

I suddenly saw telomeres in a whole new light.

我突然從全新的角度去看端粒。

I saw beyond the genes and the chromosomes

我超越了基因和染色體，

into the lives of the real people we were studying.

看到我們所研究的真實人類的生活。

And I'm a mom myself,

我自己也是個母親，

and at that moment,

在那一刻，

I was struck by the image of these women

我被這個影像震撼了：

這些女子通常靠一己之力照顧孩子，

dealing with a child with a condition

有非常難處理的疾病的孩子， 往往沒有幫手。

very difficult to deal with, often without help.

And such women, simply,

這類女子，很顯而易見，

often look worn down.

經常看起來是耗盡了精力的模樣。

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

有沒有可能她們的端粒 也被損耗掉了呢？

So our collective curiosity went into overdrive.

我們共同的好奇心 促使我們加倍努力。

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

伊莉莎為我們的第一項研究 選了一群照護母親，

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

我們想要問：她們的端粒長度

compared with the number of years that they have been caregiving

和她們照顧有慢性疾病孩童多少年

for their child with a chronic condition?

有什麼關聯？

So four years go by

所以，經過了四年，

and the day comes when all the results are in,

所有結果都進來的那一天，

and Elissa looked down at our first scatterplot

伊莉莎看著我們的 第一張資料散佈圖，

and literally gasped,

真的是倒抽了一口氣，

because there was a pattern to the data,

因為資料的確呈現出了模式，

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

且正是我們最怕存在的斜線。

It was right there on the page.

就在那裡，呈現在那一頁上。

The longer, the more years that is,

母親在照護情境中的時間

the mother had been in this caregiving situation,

越久、越多年，

no matter her age,

不論她幾歲，

the shorter were her telomeres.

她的端粒都會比較短。

And the more she perceived

而且，她若越是感受到

her situation as being more stressful,

她所處的情境有很大的壓力，

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

她的端粒酶就會越少， 她的端粒也就會越短。

So we had discovered something unheard of:

所以我們發現了以前沒聽過的事：

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

越是在長期壓力之下， 你的端粒就會越短，

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

意味著，你越可能很早就罹患疾病，

and perhaps untimely death.

也可能最終會比較早死。

Our findings meant that people's life events

我們的發現意味著， 人一生經歷的事件、

and the way we respond to these events

以及我們對這些事件的因應方式，

can change how you maintain your telomeres.

能夠改變你的端粒的維護狀況。

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

所以端粒長度並不只是 把年齡換算成年數。

Elissa's question to me,

伊莉莎一開始到我實驗室問的問題，

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

的確是個生死的問題。

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

幸運的是，在那些 資料中也藏有希望。

We noticed that some mothers,

我們注意到，有些母親

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

雖然多年來都一直 很細心照顧她們的孩子，

had been able to maintain their telomeres.

卻仍然能維持著她們的端粒。

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

仔細研究這些女性， 發現她們對壓力的恢復力很強。

Somehow they were able to experience their circumstances

她們能夠以某種方式，

不一天到晚視她們 所經歷的情況為威脅，

not as a threat day in and day out

but as a challenge,

而視為是挑戰，

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

這就導出了對於我們所有人 都非常重要的洞見：

we have control over the way we age

我們能夠控制我們老化的方式

all the way down into our cells.

且一路控制到我們的細胞。

OK, now our initial curiosity became infectious.

我們一開始的好奇心 變成是有感染力的。

Thousands of scientists from different fields

數以千計來自不同領域的科學家

added their expertise to telomere research,

把他們的專長加到了 端粒的研究當中，

and the findings have poured in.

大量的發現湧入。

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

有超過一萬份科學論文， 且還在增加中。

So several studies rapidly confirmed our initial finding

所以，有許多研究很快就 確認了我們最初的發現，

that yes, chronic stress is bad for telomeres.

是的，長期壓力對於端粒有害。

And now many are revealing

現在，許多研究指出，

that we have more control over this particular aging process

我們對於這種老化的過程 所能掌控的程度，

than any of us could ever have imagined.

遠超過任何人過去的想像。

A few examples:

舉幾個例子：

a study from the University of California, Los Angeles

洛杉磯加州大學的一篇研究，

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

對象是關於長期照顧失憶親戚的人，

and looked at their caregiver's telomere maintenance capacity

該研究探究了這些照護者的 端粒維護能力，

and found that it was improved

發現他們如果連續兩個月 每天進形某種形式的冥想，

by them practicing a form of meditation

即使只有短短十二分鐘，

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

也能改善這項能力。

Attitude matters.

態度很重要。

If you're habitually a negative thinker,

如果你是個習慣性負面思考的人，

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

你通常遇到有壓力的情境時 會產生威脅性的壓力反應，

meaning if your boss wants to see you,

意思是說，如果你的老闆想見你，

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

你自動會想：「我要被開除了。」

and your blood vessels constrict,

你的血管會收縮，

and your level of the stress hormone cortisol creeps up,

你的壓力賀爾蒙皮質醇會升高，

and then it stays up,

且一直維持很高，

and over time, that persistently high level of the cortisol

隨著時間過去， 一直持續很高的皮質醇

actually damps down your telomerase.

其實就會減弱你的端粒酶。

Not good for your telomeres.

這對你的端粒不好。

On the other hand,

另一方面，

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

如果你通常視很有壓力的事情 為要對付的挑戰，

then blood flows to your heart and to your brain,

那麼，血液就會流向 你的心臟和大腦，

and you experience a brief but energizing spike of cortisol.

你就會經歷到短暫但 讓人精力充沛的皮質醇增強。

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

託那「放馬過來吧」習慣的福，

your telomeres do just fine.

你的端粒就會好好的。

So ...

所以，

What is all of this telling us?

這一切告訴我們什麼？

Your telomeres do just fine.

你的端粒好好的。

You really do have power to change what is happening

你真的有力量可以改變你自己的端粒

to your own telomeres.

會發生什麼事。

But our curiosity just got more and more intense,

但我們的好奇心變得越來越強烈，

because we started to wonder,

因為我們開始納悶，

what about factors outside our own skin?

我們身外的因素如何呢？

Could they impact our telomere maintenance as well?

它們能否影響我們的端粒維護呢？

You know, we humans are intensely social beings.

要知道，我們人類是極為社交的動物。

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

有沒有可能我們的端粒也很社交呢？

And the results have been startling.

而結果十分驚人。

As early as childhood,

早至孩童時期，

emotional neglect, exposure to violence,

情緒忽視、接觸暴力、

bullying and racism

霸凌、及種族主義，

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

都會影響你的端粒， 且影響是長期的。

Can you imagine the impact on children

你們能想像在戰區內的孩子，

of living years in a war zone?

壽命會受到什麼樣的影響？

People who can't trust their neighbors

無法信任鄰居的人，

and who don't feel safe in their neighborhoods

在鄰坊中沒有安全感的人，

consistently have shorter telomeres.

很一致地，都有比較短的端粒。

So your home address matters for telomeres as well.

所以你住哪裡，對於端粒也很重要。

On the flip side,

反過來說，

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

緊密連結的社區、長期的婚姻、

and lifelong friendships, even,

甚至一生的友誼，

all improve telomere maintenance.

都能改善端粒的維護。

So what is all this telling us?

所以，這一切告訴我們什麼？

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

它告訴我們，我有力量 可以影響我自己的端粒，

and I also have the power to impact yours.

我也有力量可以影響你的端粒。

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

端粒科學告訴我們， 我們是多麼緊密連結在一起。

But I'm still curious.

但我仍然好奇。

I do wonder

我確實納悶，

what legacy all of us

我們所有人

會留給下一代什麼遺產？

will leave for the next generation?

Will we invest

我們是否會投資給

in the next young woman or man

接下來的年輕男、女，

peering through a microscope at the next little critter,

透過顯微鏡盯著

下一個小生物、下一坨池塘浮渣，

the next bit of pond scum,

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

對我們現今仍未知的問題感到好奇？

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

那可能是個好問題， 能夠影響全世界。

And maybe, maybe you're curious about you.

也許你對你自己很好奇。

Now that you know how to protect your telomeres,

現在你知道如何保護你的端粒了，

are you curious what are you going to do

你是否會好奇，

未來數十年你將會做些什麼 來維持好健康？

with all those decades of brimming good health?

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

現在你知道你能夠 影響他人的端粒了，

are you curious

你是否會好奇，

how will you make a difference?

你將會如何造成不同？

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

現在你知道好奇的力量 可以改變世界了，

how will you make sure that the world invests in curiosity

你要如何確保世界會為了 我們之後的世代

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

而投資在好奇心上？

Thank you.

謝謝。

(Applause)

（掌聲）