The science of cells that never get oldWhat makes our bodies age ... our skin wrinkle, our hair turn white, our immune systems weaken? Biologist Elizabeth Blackburn shares a Nobel Prize for her work finding out the answer, with the discovery of telomerase: an enzyme that replenishes the caps at the end of chromosomes, which break down when cells divide. Learn more about Blackburn's groundbreaking research -- including how we might have more control over aging than we think.
2,274,041 views April 2017~~July 2022 | Elizabeth Blackburn • Molecular biologist
Elizabeth Blackburn won a Nobel Prize for her pioneering work on telomeres and telomerase, which may play central roles in how we age. She is president of the Salk Institute and author of the New York Times Best Seller, "The Telomere Effect."
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.
00:21
Now, it was no surprise I became a scientist. Growing up far away from here, as a little girl I was deadly curious about 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 mysteries of the most basic building blocks of life, and I was fortunate to live in a society where that curiosity was valued.
00:53
Now, for me, this little pond scum critter Tetrahymena was a great way to study the fundamental mystery I 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 Tetrahymena has a lot of short linear chromosomes, around 20,000, so lots of telomeres. And I discovered that telomeres consisted of special segments of noncoding DNA right at the very ends of chromosomes.
01:47
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 cells that 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 replenishing to, 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 instructions that 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 cells can fight off bacteria and viruses, and our brain cells can save the memory of our first kiss and keep on learning throughout life.
02:52
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 it like 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.
03:37
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 sure we can keep our chromosomes intact?
03:56
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 experiments and we discovered cells do have something else. It was a previously undreamed-of enzyme that 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 telomerase that our pond scum critters never got old.
04:58
OK, now, that's an incredibly hopeful message for us humans to be receiving from pond scum, because it turns out that 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 telomeres that leads us to feel and see signs of aging. My skin cells start to die and 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 years has made clear that telomere attrition is contributing to our risks of getting cardiovascular diseases, Alzheimer's, some cancers and diabetes, the very conditions many of us die of.
06:00
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 longer for longer periods of time, extending our feelings of youthfulness and reducing the risks of all we most dread as the birthdays go by.
06:32
OK, seems like a no-brainer. Now, if my telomeres are connected to 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 aging is figure out where to buy that Costco-sized bottle of grade A organic fair trade telomerase, right? Great! Problem solved.
07:02
(Applause)
07:03
Not so fast, I'm sorry. Alas, that's not the case. OK. And why? It's because human genetics has taught us that 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.
07:57
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," ...
08:10
(Laughter)
08:14
there is something for us humans in the story of telomeres and their maintenance. But I want to get one thing clear. It isn't about enormously extending human lifespan or immortality. It's about health span. Now, health span is the number of years of your life when 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' length and hence my well-being, my health, without those downsides of cancer risks? OK?
09:02
So, it's the year 2000. Now, I've been minutely scrutinizing little teeny tiny telomeres very 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 stress on 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 --
09:34
(Laughter)
09:36
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 question changed me profoundly. See, all this time I had been thinking of telomeres as 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 chromosomes into 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 women dealing with a child with a condition very 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?
11:01
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 telomeres compared with the number of years that they have been caregiving for their child with a chronic condition? So four years go by and the day comes when all the results are in, and Elissa looked down at our first scatterplot and 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 perceived her situation as being more stressful, the lower was her telomerase and the shorter were her telomeres.
12:07
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 span and perhaps untimely death. Our findings meant that people's life events and the way we respond to these events can 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.
12:49
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 circumstances not as a threat day in and day out but as a challenge, and this has led to a very important insight for all of us: we have control over the way we age all the way down into our cells.
13:27
OK, now our initial curiosity became infectious. Thousands of scientists from different fields added 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 finding that yes, chronic stress is bad for telomeres. And now many are revealing that we have more control over this particular aging process than any of us could ever have imagined. A few examples: a study from the University of California, Los Angeles of people who are caring for a relative with dementia, long-term, and looked at their caregiver's telomere maintenance capacity and found that it was improved by them practicing a form of meditation for 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 cortisol actually damps down your telomerase. Not good for your telomeres.
15:02
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 happening to your own telomeres.
15:44
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 racism all impact your telomeres, and the effects are long-term. Can you imagine the impact on children of living years in a war zone? People who can't trust their neighbors and who don't feel safe in their neighborhoods consistently 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.
16:58
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.
17:17
But I'm still curious. I do wonder what legacy all of us will leave for the next generation? Will we invest in the next young woman or man peering 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 do with all those decades of brimming good health? And now that you know you could impact the telomeres of others, are you curious how 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 curiosity for the sake of the generations that will come after us?
18:26
Thank you.
18:27
(Applause)
Cindy Zheng-Huang, Translator
Yu Xie, Reviewer
00:01
终点是从哪开始的? 对我来说,一切都是从 这个小家伙开始。 这个可爱的微生物 是的,我觉得它很可爱, 它被称为“四膜虫”, 是一种单细胞生物, 它也被称为藻类。 没错,我的职业生涯从浮渣开始
00:21
我成为一名科学家 并不令人感到意外。 我在离这里很远的地方长大, 还是一个小女孩时 就对所有活物 感到非常的好奇。 我常常捡起有毒刺的水母 并对它们歌唱。 所以,我刚开始职业生涯的时候, 就对生命的奥秘非常的好奇 特别是那些构成生命的最基本要素。 幸运的是,我生活在 一个重视这种好奇的社会。
00:53
现在,对我来说,这种小藻类生物“四膜虫”, 是一个研究这个基本奥秘的好方法。
我最好奇的是有关: 在我们细胞中 称为染色体的那一簇簇DNA。 这是因为我对染色体的最末端,即“端粒" 这一部分非常有兴趣。 在我开始探索时, 我们所知道的就是 它们保护染色体的末端。 这在细胞分裂时很重要 真的特别重要。 但我想搞清楚端粒由什么组成, 为此,我需要许多端粒。 而可爱的小四膜虫, 拥有许多小线性染色体。 大概有两万个, 因此数量充足。 我发现端粒包含特殊区段 非编码DNA的就在染色体的最末端。
01:47
但,这里有个问题。 我们的生命都从一个细胞开始, 之后,它倍增成两个, 二个变成成四个,四个变成八个, 不断分化形成 200万兆个细胞, 组成我们成熟的身体。 而且一些细胞 必须分化几千次。 事实上,即使我站在你面前, 全身细胞正在疯狂地更新, 为了让我能站在你面前。 每次细胞分裂, 所有的DNA都必须被复制, 所有在那些染色体内部的DNA编码, 因为它们携带了重要的操作指南, 使我们的细胞保持良好的工作状态。 这样我的心脏细胞就可以 保持稳定的跳动。 但事实上,我向各位保证 它们现在并没有做到。 而我的免疫细胞, 能抵抗细菌和病毒, 还有我们的脑细胞 可以保存我们初吻的记忆, 并且保持终身学习。
02:52
但在DNA复制的过程总会有个小故障 当然,这只是生活中的事实之一。 每次细胞分裂 DNA被复制, 一些来自末端的DNA 磨损和缩短, 一些DNA端粒。 再想一想, 就像在你鞋带的末端保护帽一样 那些阻止鞋带, 或染色体磨损的东西 当那些保护措施变得太短,它就会脱落。 而那些磨损的端粒则 向细胞发送信号, “这一条DNA不再受到保护了。” 它发出一个信号,死亡的时刻到了。 所以,故事的结局。
03:37
哦,对不起,没那么快。 这不可能是故事的结局, 因为生命还没从 地球表面消逝。 所以我很好奇: 如果这样的磨损是不可避免的, 大自然究竟是怎么确保 我们可以保持染色体完整呢?
03:56
现在,还记得 池塘里的小四膜虫? 最古怪的是, 四膜虫的细胞从不变老和死亡。 它们的端粒并没有 随着时间向前而缩短, 有时甚至长得更长。 还有别的东西在起作用, 相信我,那些东西 不在任何教科书中。 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 凯罗尔和我因这项工作 共享了诺贝尔奖。 我们开始做实验, 我们发现细胞 确实有其他的东西。 这是一个以前做梦也想不到的酶。 它可以补充, 使端粒变得更长。 我们把它命名为端粒酶。 当我们去除掉实验藻的端粒酶, 它们的端粒水平下降了,死了。 所以这得感谢充足的端粒酶 我们的藻生物从不变老。
04:58
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, 从这些藻类生物中得出的。 因为结果就是, 当我们人类衰老, 我们的端粒就随之缩短。 显然这种缩短 正在使我们衰老。 一般来说你的端粒越长, 你的身体狀況就会越好。 正是这端粒的过度缩短 让我们感觉和看到衰老的迹象。 我的皮肤细胞开始死亡, 于是我开始看到细纹,皱纹。 毛发色素细胞死亡, 你就会开始看到这些灰色的头发。 免疫系统细胞死亡, 你增加了生病的风险。 事实上,20年来持续的研究都 明确表明端粒损耗, 增加了我们患心血管疾病, 老年痴呆症,某些癌症和糖尿病的风险。 这些都是现代大多数人的死亡原因。
06:00
所以我们必须考虑这个问题 到底是怎么回事? 这种损耗, 使我们看起来以及感觉老了。 我们的端粒正在加快消失。 还有那些我们觉得青春更长的人, 结果是我们的端粒保持时间长些, 更长的时间, 而正是这种延长 也延长了我们的青春感, 减少了当我们每渡过一次生日, 所感到的那种时间流逝的恐惧。
06:32
好的, 这么一说好像很简单。 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
06:43
如果我的端粒可以 被我的端粒酶更新, 那么为了扭转衰老的征兆和症状 我做的就是 弄清楚在哪里能买到 像Costco瓶子那样大小的 A级有机公平交易的端粒酶,对吗? 太好了,问题解决了.
07:02
(掌声)
07:03
但实际上并没有这么快,我很抱歉 唉,事实并非如此。 为什么呢? 这因为人类遗传学已经告诉我们, 当涉及到我们的端粒酶时, 我们人类生活在刀刃上, 好吧,简单地说, 是的,提高端粒酶的水平 确实减少某些疾病的风险, 但它也增加了某些恶性肿瘤的风险。 所以即使你能买到 Costco样大瓶的端粒酶, 而且有很多网站, 销售这种可疑产品。 但这么做的弊端就是 你可能提高了患癌症的风险。 我们并不想要那样。
07:57
现在,别担心 因为,虽然我觉得有点好笑, 现在我们很多人可能在想, 好吧,我宁愿是池塘里的水藻。
08:10
(笑声)
08:14
人类机体内 就存在着端粒维护机制。 但是我想澄清一件事, 这并不是关于 延长人类的寿命 或使人类达成永生的机制。 这是关于健康的寿命, 健康寿命是指你生命中有多少年 你没有疾病,你很健康,很有生产力, 你兴致勃勃地享受生活。 带病生存与健康寿命相反 是你生命中感觉衰老,生病和死亡的时刻。 所以问题实际就变成 好吧,如果我不能狂饮端粒酶饮料 我们是否能控制 自己端粒的长度。 因此我的良好状态,我的健康, 就不会有这些负面癌症影响的风险? 可以吗?
09:02
所以,这是2000年 现在,我已经详细检查 那小小的,极小的,极微的的端粒 快乐地过了很多年, 一个叫伊丽莎 埃佩尔的心理学家 走进我的实验室, 现在,伊丽莎专长的是 严重慢性心理压力, 于身心健康的影响. 她站在我的实验室里, 讽刺的是从那可以看到太平间入口,
09:34
(笑声)
09:36
她有一个关生有死的问题问我 “在那些长期处于压力的人群中, 端粒会发生什么变化?” 她问我。 你看,她一直在研究照护者, 特别是慢性病儿童的母亲 无论是肠道紊乱,自闭症, 凡你说得出的都有 --- 这个群体显然是长期 处于巨大心理压力之下。 我不得不说,她的问题 深深地改变了我。 你看,长期以来, 我一直在思考端粒 那些微小的分子结构, 和那控制端粒的基因。 当伊丽莎问我 有关照护者的研究。 我突然看到端粒, 在崭新的亮点之中。 我看到了超越基因和染色体之外, 进入到我们所研究的人 真实的生活之中, 我自己也是个妈妈 在那一刻, 我被这些女人的形象所触动。 照顾一个有病的孩子, 很难处理, 常常没有帮助 而这样的女人,显然, 经常看起来疲惫不堪。 那么她们的端粒 会不会也损耗了呢?
11:01
所以,我们的所有的好奇心 马上超速运转。 伊丽莎为我们第一个研究 选了一组这样的照护妈妈。 我们想要问: 端粒的长度 与她们照顾慢性病孩子的年数相比. 四年过去了, 在所有的结果都来临这一天, 伊丽莎看着 我们的第一个散点图, 简直深吸了一口气, 因为数据呈现一个模式, 正是我们最害怕 可能存在的梯度变化。 就呈现在那页上。 时间越长,年数越多, 母亲处于 在这照顾者的情况下, 不管她的年龄的大小, 她的端粒越短。 和她越感到 她的处境压力越大 她的端粒酶越低, 她的端粒越短。
12:07
所以我们发现了一些前所未闻的东西: 你承受的慢性压力越大, 你的端粒越短, 意味着你越有可能 过早患病 也许是英年早逝。 我们的研究结果意味着 人们的生活事件, 以及我们对这些事件的反应方式 可以改变 你如何维持你的端粒。 端粒长度并不只是年岁长短, 伊丽莎的问题于我而言, 就在她第一次来到我的实验室时, 的确是一个生死问题。
12:49
现在,幸运的是 隐藏在这些数据中有希望。 我们注意到一些母亲, 尽管细心照顾 她们的孩子多年, 却能够维持她们的端粒。 所以仔细研究这些女人 她们能承受压力。 不知何故她们能 经历她们的处境, 不当作一日复一日的威胁 而是作为挑战。 这给了我们所有人一个领悟:
我们可以控制自己的老化过程。 一直深入到我们的细胞。
13:27
好了,现在我们起初的好奇 变得有传染性。 成千上万的科学家 从不同的领域 加入他们的专业知识在 端粒的研究上, 研究结果也大量涌现。 超过10,000篇 科技论文与统计。 所以,有一些研究 很快证实了我们的初步发现。 是的,慢性应激 对端粒不好。 现在许多研究揭示, 我们在这种老化过程 有更多的掌控权, 比我们所能想象的更多。 举几个例子: 加利福尼亚洛杉矶大学的一项研究, 长期照顾患有痴呆症亲人, 研究他们的照顾者 端粒的维持能力, 发现它得到了改善, 通过练习一种冥想, 只需每天12分钟持续两个月。 态度很重要。 如果你习惯了消极的思考, 你通常遇到压力情形 会以威胁应激作反应, 比如,你的老板想见你, 你自然而然地想, “我就要被解雇了,” 你的血管收缩, 和你的压力荷尔蒙 皮质醇水平升高, 而且持续在那, 随着时间的推移, 这种持续高水平的皮质醇 实际上,抑制你的端粒酶, 不利于你的端粒。
15:02
另一方面, 如果你通常视有压力的事情, 作为一个有待解决的挑战, 于是,血液流向你的心脏。 和你的大脑, 你经历了一个简短的 但兴奋的皮质醇峰值。 感谢那个 “来吧”的态度, 你的端粒会没事, 所以, 这一切告诉我们什么? 你的端粒很好。 你真的有权力 改变正在发生的事情 对你自己的端粒。
15:44
但我们的好奇心 变得越来越強烈, 因为我们开始想知道, 我们自己皮肤以外的因素呢? 它们也能影响 我们的端粒维持吗? 你知道,我们人类 是极度的群居动物 我们的端粒也可能是有社会性的吗? 结果令人吃惊。 早在童年时代, 情感上的忽视、暴露在暴力之中, 欺凌和种族主义 都会影响你的端粒, 其影响是长期的。 你能想象对孩子的影响, 在战区度过多年, 人们不能信任邻居, 在他们的社区觉得不安全, 端粒长度较短。 所以你的家庭住址 对端粒也很重要。 反过来, 紧密结合的社区, 长久的婚姻, 甚至终身的友谊, 改善端粒的维持。
16:58
那么这一切告诉我们什么? 它告诉我们,我有力量 影响我自己的端粒, 我也有能力影响你的。 端粒科学告诉我们 我们是那么的连接在一起。
17:17
但我还是很好奇。 我真的想知到, 我们所有人 将遗留给下一代什么? 我们是否会投资 在下一个年轻男女, 透过显微镜窥视 下一个小动物, 下一堆绿藻, 对某个问题很好奇 我们今天都不知道是个问题? 这可能是个很好的 会影响整个世界的问题. 也许,也许你对自己很好奇。 现在你知道了 如何保护你的端粒, 你好奇你将要做什么吗? 在身体健康的几十年。 现在你知道你可以影响 其他人的端粒, 你是否好奇 你将如何改变世界? 现在你知道了 好奇心改变世界的力量, 你将如何确定 世界投资于好奇心 为了下一代,为了来人? 谢谢。
18:33
(掌声)
https://www.ted.com/talks/elizabeth_blackburn_the_science_of_cells_that_never_get_old/transcript