長生不老的細胞科學演講稿

　　Where does the end begin?Well, for me, it all began with this little fellow.This adorable organism --well, I think it’s adorable --is called Tetrahymena and it’s a single-celled creature.It’s also been known as pond scum.So that’s right, my career started with pond scum.

　　結束是從何開始的?對我來說，它開始于這個小家伙。這可愛的有機體，我認為它很可愛，它叫做四膜蟲，是種單細胞生物。它也就是池塘浮渣。是的，我的職涯始于池塘浮渣。

　　Now, it was no surprise I became a scientist.Growing up far away from here,as a little girl I was deadly curiousabout everything alive.I used to pick up lethally poisonous stinging jellyfish and sing to them.And so starting my career,I was deadly curious about fundamental mysteriesof the most basic building blocks of life,and I was fortunate to live in a society where that curiosity was valued.

　　我變成科學家并不讓人意外。我在離這里很遠的地方長大，我小時候非常有好奇心，對所有的生物都好奇。我以前會撿起有致命劇毒會螫人的水母，然后對牠們唱歌。所以，開始我的職涯時，我非常好奇，想解開最根本的謎題，想知道構成生命的基礎積木是什么，很幸運，我所在的社會很重視好奇心。

　　Now, for me, this little pond scum critter Tetrahymenawas a great way to study the fundamental mysteryI was most curious about:those bundles of DNA in our cells called chromosomes.And it was because I was curious about the very ends of chromosomes,known as telomeres.Now, when I started my quest,all we knew was that they helped protect the ends of chromosomes.It was important when cells divide.It was really important,but I wanted to find out what telomeres consisted of,and for that, I needed a lot of them.And it so happens that cute little Tetrahymenahas a lot of short linear chromosomes,around 20,000,so lots of telomeres.And I discovered that telomeres consisted of special segmentsof noncoding DNA right at the very ends of chromosomes.

　　對我而言，四膜蟲這池塘浮渣小生物是研究我最好奇的根本謎題的好方式：我們的細胞內大量的 DNA，也就是所謂的染色體。因為我對染色體的末端很好奇，也就是所謂的端粒。當我開始探索，我們只知道：它們協助保護染色體的末端。細胞分裂時，這點很重要。它相當重要，但我想要了解端粒是什么組成的，為這個目的，我需要很多端粒。剛好這個可愛的小四膜蟲有很多短短線性的染色體。大約兩萬個，所以會有很多端粒。我發現端粒包括位在染色體最末端未編碼的特殊 DNA 區段。

　　But here’s a problem.Now, we all start life as a single cell.It multiples to two.Two becomes four. Four becomes eight,and on and on to form the 200 million billion cellsthat make up our adult body.And some of those cells have to divide thousands of times.In fact, even as I stand here before you,all throughout my body, cells are furiously replenishingto, well, keep me standing here before you.So every time a cell divides, all of its DNA has to be copied,all of the coding DNA inside of those chromosomes,because that carries the vital operating instructionsthat keep our cells in good working order,so my heart cells can keep a steady beat,which I assure you they’re not doing right now,and my immune cellscan fight off bacteria and viruses,and our brain cells can save the memory of our first kissand keep on learning throughout life.

　　但，有一個問題。生命是從單細胞開始的。一個會變成兩個，兩個變成四個，四個變成八個，一路這樣下去，形成了二十萬兆個細胞，組成了成人的身體。有些細胞需要分裂數千次。事實上，即使我站在各位面前，我整個身體的細胞正瘋狂地補充，讓我能夠持續站在你們面前。每當一個細胞分裂，它所有的 DNA 都會被復制，那些染色體中所有編碼的 DNA，因為那帶有極重要的運作指示，讓我們的細胞能處于良好的工作狀態，這么一來我的心臟細胞才能保持穩定的心跳，我向各位保證，它們現在并沒做到，而我的免疫細胞，能擊退細菌和病毒，我們的頭腦細胞能儲存我們初吻的記憶，并在整個人生中持續學習。

　　But there is a glitch in the way DNA is copied.It is just one of those facts of life.Every time the cell divides and the DNA is copied,some of that DNA from the ends gets worn down and shortened,some of that telomere DNA.And think about itlike the protective caps at the ends of your shoelace.And those keep the shoelace, or the chromosome, from fraying,and when that tip gets too short, it falls off,and that worn down telomere sends a signal to the cells.The DNA is no longer being protected.It sends a signal. Time to die.So, end of story.

　　但復制 DNA 的方式有個小毛病，僅是生命的事實之一。每當細胞分裂、DNA 被復制，某些末端 DNA 會磨損縮短，一些端粒的 DNA。可以用這方式來想：就像你的鞋帶末端的保護套。它們能讓鞋帶或染色體不會被磨損，當尖端變得太短時，它就會脫落，而那被磨損掉的端粒就會發送一個訊號給細胞。「這 DNA 不再受到保護。」它發出訊號。是死亡的時候了。所以，故事結束。

　　Well, sorry, not so fast.It can’t be the end of the story,because life hasn’t died off the face of the earth.So I was curious:if such wear and tear is inevitable,how on earth does Mother Nature make surewe can keep our chromosomes intact?

　　抱歉，沒那么快。故事不可能這樣結束，因為生命還沒從地球表面上消逝。所以我很好奇：如果這種損耗是無可避免的，大自然到底要如何確保我們能保持不讓染色體受損?

　　Now, remember that little pond scum critter Tetrahymena?The craziest thing was,Tetrahymena cells never got old and died.Their telomeres weren’t shortening as time marched on.Sometimes they even got longer.Something else was at work,and believe me, that something was not in any textbook.So working in my lab with my extraordinary student Carol Greider --and Carol and I shared the Nobel Prize for this work --we began running experimentsand we discovered cells do have something else.It was a previously undreamed-of enzymethat could replenish,make longer, telomeres,and we named it telomerase.And when we removed our pond scum’s telomerase,their telomeres ran down and they died.So it was thanks to their plentiful telomerasethat our pond scum critters never got old.

　　還記得那池塘浮渣小生物四膜蟲嗎?最瘋狂的是，四膜蟲細胞從來不會變老或死亡。牠們的端粒并不會隨時間而變短。有時甚至還會變長。還有某樣東西在運作，相信我，那某樣東西并不在任何教科書中。所以，我和杰出學生凱洛葛萊德在實驗室中合作──凱洛和我共享這項研究贏得的諾貝爾獎──我們開始進行實驗，我們發現細胞的確有其他的東西。是先前意想不到的酶(酵素)，它能補充端粒，讓端粒更長，我們將它命名為「端粒酶」。當我們移除池塘浮渣的端粒酶后，牠們的端粒就會耗盡而死亡。所以要歸功于豐富的端粒酶，我們的池塘浮渣才能永生不老。

　　OK, now, that’s an incredibly hopeful messagefor us humans to be receiving from pond scum,because it turns outthat as we humans age, our telomeres do shorten,and remarkably,that shortening is aging us.Generally speaking,the longer your telomeres,the better off you are.It’s the overshortening of telomeresthat leads us to feel and see signs of aging.My skin cells start to dieand I start to see fine lines, wrinkles.Hair pigment cells die.You start to see gray.Immune system cells die.You increase your risks of getting sick.In fact, the cumulative research from the last 20 yearshas made clear that telomere attritionis contributing to our risks of getting cardiovascular diseases,Alzheimer’s, some cancers and diabetes,the very conditions many of us die of.

　　那是我們人類能從池塘浮渣身上得到的一個非常有希望的訊息，因為結果發現，隨著我們人類年紀增長，我們的端粒確實會變短，很驚人的是，那縮短現象讓我們變老。一般來說，你的端粒越長，你的狀況就會越好。是端粒過度減短的現象導致我們會感到及看到老化的征象。我的皮膚細胞開始死亡，我就會開始看到線條、皺紋。頭發色素細胞死亡，你就會開始看到白發。免疫細胞死亡，你被攻擊的風險就會提升。事實上，過去二十年所累積的研究清楚地指出，端粒損耗可能造成罹患像是：心血管疾病、阿滋海默癥、某些癌癥，以及糖尿病等許多致死疾病的風險。

　　And so we have to think about this.What is going on?This attrition,we look and we feel older, yeah.Our telomeres are losing the war of attrition faster.And those of us who feel youthful longer,it turns out our telomeres are staying longerfor longer periods of time,extending our feelings of youthfulnessand reducing the risks of all we most dreadas the birthdays go by.

　　所以我們得要想想這一點。發生了什么事?這種損耗，我們看起來且感覺起來變老了。我們的端粒在損耗之戰中敗退得很快。至于覺得年輕時間比較長的人，結果發現是端粒能留比較久，比較長的時間，延長我們對于年輕的感覺，并減少我們隨著每個生日過去而最害怕的那些風險。

　　OK,seems like a no-brainer.Now, if my telomeres are connectedto how quickly I’m going to feel and get old,if my telomeres can be renewed by my telomerase,then all I have to do to reverse the signs and symptoms of agingis figure out where to buy that Costco-sized bottleof grade A organic fair trade telomerase, right?Great! Problem solved.

　　好。似乎很簡單。如果我的端粒和我多快感到變老及實際變老是有關聯的，如果我能用端粒酶來復原端粒，那么若我想要反轉老化的征兆和癥狀，就是要找個地方買像好市多那樣超大罐、A 級、有機、公平貿易的端粒酶，對吧?好極了!問題解決。

　　(Applause)

　　(掌聲)

　　Not so fast, I’m sorry.Alas, that’s not the case.OK. And why?It’s because human genetics has taught usthat when it comes to our telomerase,we humans live on a knife edge.OK, simply put,yes, nudging up telomerase does decrease the risks of some diseases,but it also increases the risks of certain and rather nasty cancers.So even if you could buy that Costco-sized bottle of telomerase,and there are many websites marketing such dubious products,the problem is you could nudge up your risks of cancers.And we don’t want that.

　　很抱歉，沒那么快。唉，并不是那樣的。那為什么呢?因為人類遺傳學教導我們，談到我們的端粒酶時，我們人類是住在刀緣上的。簡單來說，是的，增加端粒酶的確可以減少一些疾病的風險，但同時也會增加某些很糟糕的癌癥的風險。所以，就算你能買到像好市多那樣超大罐的端粒酶，有許多網站在行銷這類可疑的'產品，問題是你有可能增加罹癌的風險。我們不想要那樣。

　　Now, don’t worry,and because, while I think it’s kind of funny that right now,you know, many of us may be thinking,well, I’d rather be like pond scum.

　　別擔心，因為，雖然我覺得有點好笑，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 humansin the story of telomeres and their maintenance.But I want to get one thing clear.It isn’t about enormously extending human lifespanor immortality.It’s about health span.Now, health span is the number of years of your lifewhen you’re free of disease,you’re healthy, you’re productive,you’re zestfully enjoying life.Disease span, the opposite of health span,is the time of your life spent feeling old and sick and dying.So the real question becomes,OK, if I can’t guzzle telomerase,do I have control over my telomeres’ lengthand hence my well-being, my health,without those downsides of cancer risks?OK?

　　在這關于端粒以及維護端粒的真相中還是有我們人類可以學習之處。但我想先澄清一件事。重點并不是將人類壽命期間延長很多或是永生不死。重點是「健康期間」。健康期間，就是你人生中有多少年是沒有疾病、很健康、有生產力、能夠熱情享受人生的。相對于健康期間的「疾病期間」，指的就是你人生中有多長時間覺得自己老、病、和垂死。所以，真正的問題變成是，如果我無法狂飲端粒酶，我是否能控制端粒酶的長度，進而控制我的福祉、我的健康，而沒有癌癥風險的壞處?好嗎?

　　So, it’s the year 20xx.Now, I’ve been minutely scrutinizing little teeny tiny telomeresvery happily for many years,when into my lab walks a psychologist named Elissa Epel.Now, Elissa’s expertise is in the effects of severe, chronic psychological stresson our mind’s and our body’s health.And there she was standing in my lab,which ironically overlooked the entrance to a mortuary, and --

　　所以，那是 20xx 年。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，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。伊莉莎的專長在于嚴重慢性心理壓力對于我們身、心健康的影響。她出現在我的實驗室，很諷刺的是從實驗室可以眺望停尸間的入口，而且──

　　(Laughter)

　　(笑聲)

　　And she had a life-and-death question for me.What happens to telomeres in people who are chronically stressed?she asked me.You see, she’d been studying caregivers,and specifically mothers of children with a chronic condition,be it gut disorder,be it autism, you name it --a group obviously under enormous and prolonged psychological stress.I have to say, her questionchanged me profoundly.See, all this time I had been thinking of telomeresas those miniscule molecular structures that they are,and the genes that control telomeres.And when Elissa asked me about studying caregivers,I suddenly saw telomeres in a whole new light.I saw beyond the genes and the chromosomesinto the lives of the real people we were studying.And I’m a mom myself,and at that moment,I was struck by the image of these womendealing with a child with a conditionvery difficult to deal with,often without help.And such women, simply,often look worn down.So was it possible their telomeres were worn down as well?

　　她有個生死問題要問我。「有慢性壓力的人，他們的端粒會發生什么事?」她這樣問我。她一直在研究照護者，特別慢性病孩童的母親，可能是腸病，可能是自閉癥，任何你想得到的──這個族群很顯然處在巨大且長期的心理壓力之下。我不得不說，她的問題深深改變了我。一直以來，我從小分子結構的角度來思考端粒和控制端粒的基因。當伊莉莎問我關于照護者的問題時，我突然從全新的角度去看端粒。我超越了基因和染色體，看到我們所研究的真實人類的生活。我自己也是個母親，在那一刻，我被這個影像震撼了：這些女子通常靠一己之力照顧孩子，有非常難處理的疾病的孩子，往往沒有幫手。這類女子，很顯而易見，經常看起來是耗盡了精力的模樣。有沒有可能她們的端粒也被損耗掉了呢?

　　So our collective curiosity went into overdrive.Elissa selected for our first study a group of such caregiving mothers,and we wanted to ask:What’s the length of their telomerescompared with the number of years that they have been caregivingfor their child with a chronic condition?So four years go byand the day comes when all the results are in,and Elissa looked down at our first scatterplotand literally gasped,because there was a pattern to the data,and it was the exact gradient that we most feared might exist.It was right there on the page.The longer, the more years that is,the mother had been in this caregiving situation,no matter her age,the shorter were her telomeres.And the more she perceivedher situation as being more stressful,the lower was her telomerase and the shorter were her telomeres.

　　我們共同的好奇心促使我們加倍努力。伊莉莎為我們的第一項研究選了一群照護母親，我們想要問：她們的端粒長度和她們照顧有慢性疾病孩童多少年有什么關聯?所以，經過了四年，所有結果都進來的那一天，伊莉莎看著我們的第一張資料散布圖，真的是倒抽了一口氣，因為資料的確呈現出了模式，且正是我們最怕存在的斜線。就在那里，呈現在那一頁上。母親在照護情境中的時間越久、越多年，不論她幾歲，她的端粒都會比較短。而且，她若越是感受到她所處的情境有很大的壓力，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:the more chronic stress you are under,the shorter your telomeres,meaning the more likely you were to fall victim to an early disease spanand perhaps untimely death.Our findings meant that people’s life eventsand the way we respond to these eventscan change how you maintain your telomeres.So telomere length wasn’t just a matter of age counted in years.Elissa’s question to me,back when she first came to my lab, indeed had been a life-and-death question.

　　所以我們發現了以前沒聽過的事：越是在長期壓力之下，你的端粒就會越短，意味著，你越可能很早就罹患疾病，也可能最終會比較早死。我們的發現意味著，人一生經歷的事件、以及我們對這些事件的因應方式，能夠改變你的端粒的維護狀況。所以端粒長度并不只是把年齡換算成年數。伊莉莎一開始到我實驗室問的問題，的確是個生死的問題。

　　Now, luckily, hidden in that data there was hope.We noticed that some mothers,despite having been carefully caring for their children for many years,had been able to maintain their telomeres.So studying these women closely revealed that they were resilient to stress.Somehow they were able to experience their circumstancesnot as a threat day in and day outbut as a challenge,and this has led to a very important insight for all of us:we have control over the way we ageall the way down into our cells.

　　幸運的是，在那些資料中也藏有希望。我們注意到，有些母親雖然多年來都一直很細心照顧她們的孩子，卻仍然能維持著她們的端粒。仔細研究這些女性，發現她們對壓力的恢復力很強。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，而視為是挑戰，這就導出了對于我們所有人都非常重要的洞見：我們能夠控制我們老化的方式且一路控制到我們的細胞。

　　OK, now our initial curiosity became infectious.Thousands of scientists from different fieldsadded their expertise to telomere research,and the findings have poured in.It’s up to over 10,000 scientific papers and counting.So several studies rapidly confirmed our initial findingthat yes, chronic stress is bad for telomeres.And now many are revealingthat we have more control over this particular aging processthan any of us could ever have imagined.A few examples:a study from the University of California, Los Angelesof people who are caring for a relative with dementia, long-term,and looked at their caregiver’s telomere maintenance capacityand found that it was improvedby them practicing a form of meditationfor as little as 12 minutes a day for two months.Attitude matters.If you’re habitually a negative thinker,you typically see a stressful situation with a threat stress response,meaning if your boss wants to see you,you automatically think, "I’m about to be fired,"and your blood vessels constrict,and your level of the stress hormone cortisol creeps up,and then it stays up,and over time, that persistently high level of the cortisolactually damps down your telomerase.Not good for your telomeres.

　　我們一開始的好奇心變成是有感染力的。數以千計來自不同領域的科學家把他們的專長加到了端粒的研究當中，大量的發現涌入。有超過一萬份科學論文，且還在增加中。所以，有許多研究很快就確認了我們最初的發現，是的，長期壓力對于端粒有害。現在，許多研究指出，我們對于這種老化的過程所能掌控的程度，遠超過任何人過去的想像。舉幾個例子：洛杉磯加州大學的一篇研究，對象是關于長期照顧失憶親戚的人，該研究探究了這些照護者的端粒維護能力，發現他們如果連續兩個月每天進形某種形式的冥想，即使只有短短十二分鐘，也能改善這項能力。態度很重要。如果你是個習慣性負面思考的人，你通常遇到有壓力的情境時會產生威脅性的壓力反應，意思是說，如果你的老板想見你，你自動會想：「我要被開除了。」你的血管會收縮，你的壓力賀爾蒙皮質醇會升高，且一直維持很高，隨著時間過去，一直持續很高的皮質醇其實就會減弱你的端粒酶。這對你的端粒不好。

　　On the other hand,if you typically see something stressful as a challenge to be tackled,then blood flows to your heart and to your brain,and you experience a brief but energizing spike of cortisol.And thanks to that habitual "bring it on" attitude,your telomeres do just fine.So ...What is all of this telling us?Your telomeres do just fine.You really do have power to change what is happeningto your own telomeres.

　　另一方面，如果你通常視很有壓力的事情為要對付的挑戰，那么，血液就會流向你的心臟和大腦，你就會經歷到短暫但讓人精力充沛的皮質醇增強。托那「放馬過來吧」習慣的福，你的端粒就會好好的。所以，這一切告訴我們什么?你的端粒好好的。你真的有力量可以改變你自己的端粒會發生什么事。

　　But our curiosity just got more and more intense,because we started to wonder,what about factors outside our own skin?Could they impact our telomere maintenance as well?You know, we humans are intensely social beings.Was it even possible that our telomeres were social as well?And the results have been startling.As early as childhood,emotional neglect, exposure to violence,bullying and racismall impact your telomeres,and the effects are long-term.Can you imagine the impact on childrenof living years in a war zone?People who can’t trust their neighborsand who don’t feel safe in their neighborhoodsconsistently have shorter telomeres.So your home address matters for telomeres as well.On the flip side,tight-knit communities,being in a marriage long-term,and lifelong friendships, even,all improve telomere maintenance.

　　但我們的好奇心變得越來越強烈，因為我們開始納悶，我們身外的因素如何呢?它們能否影響我們的端粒維護呢?要知道，我們人類是極為社交的動物。有沒有可能我們的端粒也很社交呢?而結果十分驚人。早至孩童時期，情緒忽視、接觸暴力、霸凌、及種族主義，都會影響你的端粒，且影響是長期的。你們能想像在戰區內的孩子，壽命會受到什么樣的影響?無法信任鄰居的人，在鄰坊中沒有安全感的人，很一致地，都有比較短的端粒。所以你住哪里，對于端粒也很重要。反過來說，緊密連結的社區、長期的婚姻、甚至一生的友誼，都能改善端粒的維護。

　　So what is all this telling us?It’s telling us that I have the power to impact my own telomeres,and I also have the power to impact yours.Telomere science has told us just how interconnected we all are.

　　所以，這一切告訴我們什么?它告訴我們，我有力量可以影響我自己的端粒，我也有力量可以影響你的端粒。端粒科學告訴我們，我們是多么緊密連結在一起。

　　But I’m still curious.I do wonderwhat legacy all of uswill leave for the next generation?Will we investin the next young woman or manpeering through a microscope at the next little critter,the next bit of pond scum,curious about a question we don’t even know today is a question?It could be a great question that could impact all the world.And maybe, maybe you’re curious about you.Now that you know how to protect your telomeres,are you curious what are you going to dowith all those decades of brimming good health?And now that you know you could impact the telomeres of others,are you curioushow will you make a difference?And now that you know the power of curiosity to change the world,how will you make sure that the world invests in curiosityfor the sake of the generations that will come after us?

　　但我仍然好奇。我確實納悶，我們所有人會留給下一代什么遺產?我們是否會投資給接下來的年輕男、女，透過顯微鏡盯著下一個小生物、下一坨池塘浮渣，對我們現今仍未知的問題感到好奇?那可能是個好問題，能夠影響全世界。也許你對你自己很好奇。現在你知道如何保護你的端粒了，你是否會好奇，未來數十年你將會做些什么來維持好健康?現在你知道你能夠影響他人的端粒了，你是否會好奇，你將會如何造成不同?現在你知道好奇的力量可以改變世界了，你要如何確保世界會為了我們之后的世代而投資在好奇心上?

　　Thank you.

　　謝謝。

　　(Applause)

　　(掌聲)

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