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.
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.
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.
对我而言，四膜虫这池塘浮渣小生物是研究我最好奇的根本谜题的好方式：我们的细胞内大量的 DNA，也就是所谓的染色体。因为我对染色体的末端很好奇，也就是所谓的端粒。当我开始探索，我们只知道：它们协助保护染色体的末端。细胞分裂时，这点很重要。它相当重要，但我想要了解端粒是什么组成的，为这个目的，我需要很多端粒。刚好这个可爱的小四膜虫有很多短短线性的染色体。大约两万个，所以会有很多端粒。我发现端粒包括位在染色体最末端未编码的特殊 DNA 区段。
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，有一个问题。生命是从单细胞开始的。一个会变成两个，两个变成四个，四个变成八个，一路这样下去，形成了二十万兆个细胞，组成了成人的身体。有些细胞需要分裂数千次。事实上，即使我站在各位面前，我整个身体的细胞正疯狂地补充，让我能够持续站在你们面前。每当一个细胞分裂，它所有的 DNA 都会被复制，那些染色体中所有编码的 DNA，因为那带有极重要的运作指示，让我们的细胞能处于良好的工作状态，这么一来我的心脏细胞才能保持稳定的心跳，我向各位保证，它们现在并没做到，而我的免疫细胞，能击退细菌和病毒，我们的头脑细胞能储存我们初吻的记忆，并在整个人生中持续学习。
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.
但复制 DNA 的方式有个小毛病，仅是生命的事实之一。每当细胞分裂、DNA 被复制，某些末端 DNA 会磨损缩短，一些端粒的 DNA。可以用这方式来想：就像你的鞋带末端的保护套。它们能让鞋带或染色体不会被磨损，当尖端变得太短时，它就会脱落，而那被磨损掉的端粒就会发送一个讯号给细胞。「这 DNA 不再受到保护。」它发出讯号。是死亡的时候了。所以，故事结束。
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?
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.
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.
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.
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.
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.
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.
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?
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。多年来，我很快乐地、分分钟钟地持续仔细观察著那些极微小的端粒，直到有一天，名叫伊莉莎埃佩尔的心理学家走入了我的实验室。伊莉莎的专长在于严重慢性心理压力对于我们身、心健康的影响。她出现在我的实验室，很讽刺的是从实验室可以眺望停尸间的入口，而且──
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?
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.
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.
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.
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.
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.
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.
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.
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?