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The science of cells that never get old细胞科学万岁 [复制链接]

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The science of cells that never get old
What 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.

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.

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.

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.

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.

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?

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.

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.

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.

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.


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.

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 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?

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 --


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?

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.

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.

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.

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.

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.

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.

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 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?

Thank you.


Cindy Zheng-Huang, Translator
Yu Xie, Reviewer

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

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。

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。

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。

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。

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?

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。

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。

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。

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

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.


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。

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。


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?

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,


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?

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。

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。

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。

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。

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。

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。

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。

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。



只看该作者 沙发  发表于: 2022-07-14
Could your thoughts make you age faster?
Apr 26, 2017 / Elizabeth Blackburn + Elissa Epel
Researchers are finding that your mental patterns could be harming your telomeres — essential parts of the cell’s DNA — and affecting your life and health. Nobel Prize-winning scientist Elizabeth Blackburn and health psychologist Elissa Epel explain.
How can one person bask in the sunshine of good health, while another person looks old before her time? Humans have been asking this question for millennia, and recently, it’s becoming clearer and clearer to scientists that the differences between people’s rates of aging lie in the complex interactions among genes, social relationships, environments and lifestyles. Even though you are born with a particular set of genes, the way you live can influence how they express themselves. Some lifestyle factors may even turn genes on or shut them off.

Deep within the genetic heart of all our cells are telomeres, or repeating segments of noncoding DNA that live at the ends of the chromosomes. They form caps at the ends of the chromosomes and keep the genetic material from unraveling. Shortening with each cell division, they help determine how fast a cell ages. When they become too short, the cell stops dividing altogether. This isn’t the only reason a cell can become senescent — there are other stresses on cells we don’t yet understand very well — but short telomeres are one of the major reasons human cells grow old. We’ve devoted most of our careers to studying telomeres, and one extraordinary discovery from our labs (and seen at other labs) is that telomeres can actually lengthen.

What this means: Aging is a dynamic process that could possibly be accelerated or slowed — and, in some aspects, even reversed. To an extent, it has surprised us and the rest of the scientific community that telomeres do not simply carry out the commands issued by your genetic code. Your telomeres are listening to you. The foods you eat, your response to challenges, the amount of exercise you get, and many other factors appear to influence your telomeres and can prevent premature aging at the cellular level. One of the keys to enjoying good health is simply doing your part to foster healthy cell renewal.

People who score high on measures of cynical hostility have shorter telomeres.

Scientists have learned that several thought patterns appear to be unhealthy for telomeres, and one of them is cynical hostility. Cynical hostility is defined by high anger and frequent thoughts that other people cannot be trusted. Someone with hostility doesn’t just think, “I hate to stand in long lines at the grocery store”; they think, “That other shopper deliberately sped up and beat me to my rightful position in the line!” — and then they seethe.

People who score high on measures of cynical hostility tend to get more cardiovascular disease, metabolic disease and often die at younger ages. They also have shorter telomeres. In a study of British civil servants, men who scored high on measures of cynical hostility had shorter telomeres than men whose hostility scores were low. The most hostile men were 30 percent more likely to have a combination of short telomeres and high telomerase (an enzyme in cells that helps keep telomeres in good shape) — a profile that seems to reflect the unsuccessful attempts of telomerase to protect telomeres when they are too short.

These men had the opposite of a healthy response to stress. Ideally, your body responds to stress with a spike in cortisol and blood pressure, followed by a quick return to normal levels. Instead, when these men were exposed to stress, their diastolic blood pressure and cortisol levels were blunted, a sign their stress response was, basically, broken from overuse. Their systolic blood pressure increased, but instead of returning to normal levels, it stayed elevated for a long time afterward.

The hostile men also had fewer social connections and less optimism. In terms of their physical and psychosocial health, they were highly vulnerable to an early disease-span, the years in a person’s life marked by the diseases of aging, which include cardiovascular disease, arthritis, a weakened immune system and more. Women tend to have lower hostility — and it’s less related to heart disease for them — but there are other psychological culprits affecting women’s health, such as depression.

When you ruminate, stress sticks around in the body long after the reason for the stress is over.

Pessimism is the second thought pattern that has been shown to have negative effects on telomeres. When our research team conducted a study on pessimism and telomere length, we found that people who scored high on a pessimism inventory had shorter telomeres. This was a small study of about 35 women, but similar results have been found in other studies, including a study of over 1,000 men. It also fits with a large body of evidence that pessimism is a risk factor for poor health. When pessimists develop an aging-related illness, like cancer or heart disease, the illness tends to progress faster. Like cynically hostile people — and people with short telomeres, in general — they tend to die earlier.

Rumination — the act of rehashing problems over and over — is the third destructive thought pattern. How do you tell rumination from harmless reflection? Reflection is the natural, introspective analysis about why things happen a certain way. It may cause you some healthy discomfort, but rumination feels awful and never leads to a solution, only to more ruminating.

When you ruminate, stress sticks around in the body long after the reason for the stress is over, in the form of prolonged high blood pressure, elevated heart rate, and higher levels of cortisol. Your vagus nerve, which helps you feel calm and keeps your heart and digestive system steady, withdraws its activity — and remains withdrawn long after the stressor is over.

In a study, we examined daily stress responses in healthy women who were family caregivers. The more the women ruminated after a stressful event, the lower the telomerase in their aging CD8 cells (the crucial immune cells that send out proinflammatory signals when they are damaged). People who ruminate experience more depression and anxiety, which are, in turn, associated with shorter telomeres.

The fourth thought pattern is thought suppression, the attempt to push away unwanted thoughts and feelings. The late Daniel Wegener, a Harvard social psychologist, once came across this line from the great Russian writer Leo Tolstoy: “Try to pose for yourself this task: not to think of a polar bear, and you will see that the cursed thing will come to mind every minute.” Wegener put this idea to the test through a series of experiments and identified a phenomenon he called ironic error, meaning that the more forcefully you push your thoughts away, the louder they call out for your attention.

Ironic error may also be harmful to telomeres. If we try to manage stressful thoughts by sinking the bad thoughts into the deepest waters of our subconscious, it can backfire. The chronically stressed brain’s resources are already taxed — we call this cognitive load — making it even harder to successfully suppress thoughts. Instead of less stress, we get more.

In a small study, greater avoidance of negative feelings and thoughts was associated with shorter telomeres. Avoidance alone is probably not enough to harm telomeres, but it can lead to chronic stress arousal and depression, both of which may shorten your telomeres.

Thought awareness can promote stress resilience. With time, you learn to encounter ruminations and say, “That’s just a thought.”

The final thought pattern is mind wandering. Harvard University psychologists Matthew Killingsworth (TED Talk: Want to be happier? Stay in the moment) and Daniel Gilbert (TED Talk: The surprising science of happiness) used a “track your happiness” iPhone app to ask thousands of people questions about what activity they are engaged in, what their minds are doing, and how happy they are. Killingsworth and Gilbert discovered people spend half of the day thinking about something other than what we’re doing. They also found that when people are not thinking about what they’re doing, they’re not as happy as when they’re engaged. In particular, negative mind wandering — thinking negative thoughts, or wishing you were somewhere else — was more likely to lead to unhappiness in their next moments.

Together with Eli Puterman, we studied close to 250 healthy, low-stress women who ranged from 55 to 65 years old and assessed their tendency to mind-wander. We asked them two questions: “How often in the past week have you had moments when you felt totally focused or engaged in doing what you were doing at the moment? How often in the past week have you had any moments when you felt you didn’t want to be where you were, or doing what you were doing at the moment?” Then we measured the women’s telomeres.

The women with the highest levels of self-reported mind-wandering had telomeres that were shorter by around 200 base pairs. (To put this in context, a typical 35-year-old has roughly 7,500 base pairs of telomeres; a 65-year-old, 4,800 base pairs.) This was regardless of how much stress they had in their lives.

Some mind-wandering can be creative, of course. But when you are thinking negative thoughts about the past, you are more likely to be unhappy, and you may possibly even experience higher levels of resting stress hormones.

The negative thought patterns we’ve described are automatic, exaggerated and controlling. They take over your mind; it’s as if they tie a blindfold around your brain so you can’t see what is really going on around you. But when you become more aware of your thoughts, you take off the blindfold. You won’t necessarily stop the thoughts, but you have more clarity. Activities that promote better thought awareness include most types of meditation, along with most forms of mind-body exercises, including long-distance running.

Thought awareness can promote stress resilience. With time, you learn to encounter your own ruminations or problematic thoughts and say, “That’s just a thought. It’ll fade.” That is a secret about the human mind: We don’t need to believe everything our thoughts tell us. Or, as the bumper sticker says, “Don’t believe everything you think.”

Excerpted from the new book The Telomere Effect: A Revolutionary Approach to Living Younger, Healthier, Longer by Elizabeth Blackburn and Elissa Epel. Reprinted with permission from Grand Central Publishing, a division of Hachette Book Group, Inc. © 2017 Elizabeth Blackburn and Elissa Epel.
研究人员发现,你的心理模式可能会损害你的端粒——细胞 DNA 的重要组成部分——并影响你的生活和健康。诺贝尔奖获得者科学家伊丽莎白布莱克本和健康心理学家艾丽莎埃佩尔解释道。

在我们所有细胞的遗传心脏深处,有端粒,或位于染色体末端的非编码 DNA 的重复片段。它们在染色体末端形成帽子,防止遗传物质散开。随着每次细胞分裂缩短,它们有助于确定细胞老化的速度。当它们变得太短时,细胞会完全停止分裂。这不是细胞衰老的唯一原因——我们还不太了解细胞还有其他压力——但短端粒是人类细胞变老的主要原因之一。我们的大部分职业生涯都致力于研究端粒,我们实验室(以及在其他实验室看到的)的一个非凡发现是端粒实际上可以延长。



科学家们了解到,有几种思维模式似乎对端粒不健康,其中之一是愤世嫉俗的敌意。愤世嫉俗的敌意是由高度的愤怒和频繁的想法来定义的,其他人无法信任。怀有敌意的人不仅会想,“我讨厌在杂货店排长队”;他们认为,“那个购物者故意加速并把我打到了我应得的排队位置!” ——然后他们沸腾了。

在愤世嫉俗的敌意方面得分高的人往往会患上更多的心血管疾病、代谢疾病,并且往往会在年轻时死亡。它们的端粒也较短。在一项针对英国公务员的研究中,在愤世嫉俗的敌意方面得分高的男性比敌意得分低的男性端粒更短。最具敌意的男性同时拥有短端粒和高端粒酶(细胞中的一种酶,有助于保持端粒保持良好状态)的可能性要高出 30%——这一特征似乎反映了端粒酶在保护端粒时未能成功的尝试。太短。




悲观主义是第二种被证明对端粒有负面影响的思维模式。当我们的研究团队对悲观情绪和端粒长度进行研究时,我们发现在悲观情绪清单中得分高的人端粒较短。这是一项针对约 35 名女性的小型研究,但在其他研究中也发现了类似的结果,包括一项针对 1,000 多名男性的研究。它也符合大量证据表明悲观情绪是健康状况不佳的危险因素。当悲观主义者患上与衰老相关的疾病时,如癌症或心脏病,疾病往往进步更快。就像愤世嫉俗的敌对人——一般来说,端粒短的人——他们往往死得更早。



在一项研究中,我们检查了作为家庭照顾者的健康女性的日常压力反应。女性在压力事件后反省得越多,其老化的 CD8 细胞(受损时发出促炎信号的关键免疫细胞)中的端粒酶就越低。反刍的人会经历更多的抑郁和焦虑,而这又与端粒较短有关。





最后的思维模式是走神。哈佛大学心理学家 Matthew Killingsworth(TED 演讲:想要更快乐吗?留在当下)和 Daniel Gilbert(TED 演讲:幸福的惊人科学)使用“追踪你的幸福”iPhone 应用程序向成千上万的人询问关于什么活动的问题他们参与其中,他们的思想在做什么,他们有多快乐。 Killingsworth 和 Gilbert 发现人们花了半天时间思考我们正在做的事情以外的事情。他们还发现,当人们不思考自己在做什么时,他们并不像订婚时那样快乐。特别是,消极的思想游荡——想消极的想法,或者希望你在其他地方——更有可能导致他们接下来的时刻不快乐。

我们与 Eli Puterman 一起研究了近 250 名 55 至 65 岁的健康、低压力的女性,并评估了她们走神的倾向。我们问了他们两个问题:“在过去的一周里,你有多少次感到完全专注或专注于你目前正在做的事情?在过去的一周里,你有多少次觉得自己不想待在原地,或者不想做你此刻正在做的事情?”然后我们测量了女性的端粒。

自我报告的走神水平最高的女性的端粒短了大约 200 个碱基对。 (为了说明这一点,一个典型的 35 岁的人大约有 7,500 个碱基对端粒;一个 65 岁的人有 4,800 个碱基对。)这与他们生活中的压力无关。



思想意识可以促进压力恢复。 随着时间的推移,你学会遇到自己的沉思或有问题的想法,然后说:“那只是一个想法。 会褪色的。” 这是关于人类思想的一个秘密:我们不需要相信我们的思想告诉我们的一切。 或者,正如保险杠贴纸所说,“不要相信你所想的一切。”

摘自 Elizabeth Blackburn 和 Elissa Epel 的新书《端粒效应:一种更年轻、更健康、更长寿的革命性方法》。 经 Hachette Book Group, Inc. 旗下部门 Grand Central Publishing 许可转载。 © 2017 Elizabeth Blackburn 和 Elissa Epel。


只看该作者 板凳  发表于: 2022-07-14
Live From TED2017 TED Conferences
The puzzle of aging: Elizabeth Blackburn speaks at TED2017
Posted by: Rebekah Barnett April 27, 2017 at 9:09 pm EDT

Nobel-winning biologist Elizabeth Blackburn studies how humans age — and the hidden factors that might explain differences in how age affects different people. She speaks at TED2017, April 27, 2017, Vancouver, BC, Canada. Photo: Bret Hartman / TED

For Nobel Prize-winning biologist Elizabeth Blackburn, it all began with pond scum. She was curious about chromosomes, and specifically the caps at the ends of chromosomes, known as telomeres, and pond scum provided an ample supply for her research. Her curiosity sent her on a journey that shed light on one of humanity’s biggest, and oldest, questions — why and how we age.

Telomeres are special sections of noncoding DNA at the end of chromosomes that, like the plastic tips at the end of shoelaces, protect our coding DNA during cell division. Each time a cell divides, all of its genetic information has to be copied, but due to a glitch in how DNA is copied, telomeres get worn down and shortened. Telomeres help protect our coding DNA from being worn down during cell division by sacrificing themselves. Eventually, worn-down telomeres send a signal to cells that the coding DNA is at risk and it’s time for the cell to die. Based on this research, Blackburn concluded that telomere shortening was simply a fact of aging, but it turned out to be far from the full story.

With colleague Carol Greider, she noticed something strange. Pond scum cells never got old and died. “Their telomeres weren’t shortening as time marched on. Sometimes they even got longer,” she says. “Something else was at work.”

The mystery led them to the discovery of a previously undreamed-of enzyme, telomerase, which helps replenish telomeres. “When we removed telomerase in pond scum, their cells wore down and they died,” she says. In other words, telomerase can slow, prevent or even reverse telomere shortening caused by cell division and, as we’ll see, exacerbated by the stresses of life.

(Warning: unless you mistakenly think at this point that the puzzle of aging has been solved and all you have to do is get your hands on a bottle of telomerase, Blackburn is careful to stress that too much telomerase can actually be a bad thing, increasing your risk of cancer.)

“Our telomeres shorten as we age, and that’s aging us,” says Blackburn. Telomere shortening has been linked to increased risk of cardiovascular disease, cancer, diabetes and Alzheimer’s — the diseases that many of us eventually die of.

However, telomere shortening doesn’t happen at the same rate in everyone. For some, it happens slowly, extending the healthy, productive years of life, what Blackburn calls your “healthspan.” For others, it happens faster, and the disease span — the years of feeling old and sick — comes more quickly.

Blackburn began to wonder whether we had any control over our telomere length — and thus our health and wellbeing. The answer came when psychologist Elissa Epel walked into her lab. Appel studied the effects of severe chronic psychological stress, focusing on caregivers to children with a chronic disorder, and she wanted to know what happened to telomeres in the chronically stressed.

“When she asked about this, I suddenly saw telomeres in a whole light,” says Blackburn, “I saw beyond genes and chromosomes into the lives of the real people we were studying.”

Appel and Blackburn conducted their first study together on a group of caregiving mothers. When the results came in, Appel gasped. “There was a pattern,” recalls Blackburn. “It was the exact gradient we most feared might exist.” The more years the mother had been a caregiver, the shorter her telomeres, and the more the mother perceived her situation as stressful, the lower her telomerase and the shorter her telomeres.

However, “hidden in that data was hope,” says Blackburn. A small group of mothers, despite having cared for their children for years, had managed to maintain their telomeres. “They were resilient to stress,” she explains. They discovered the difference in how the mothers responded to the stress. The mothers with resilient telomeres didn’t experience stress as a threat but as a challenge. “People’s life events and the way they respond to those events can influence how they maintain telomeres,” explains Blackburn.

Intrigued by Blackburn and Appel’s research, other scientists began to explore the mysteries of telomeres, too. The results were astonishing. In one study, researchers found that caregivers of relatives with dementia who practiced meditation 12 minutes a day for two months had a 43 percent boost in telomerase. Others found that emotional neglect, exposure to violence, bullying and racism in childhood all have a long-term impact on telomeres. In contrast, tight-knit communities, lifelong friendships and long-term marriage can protect them.

“I have the power to impact my own telomeres, and I also have the power to impact yours,” says Blackburn. “Telomere science has told us just how interconnected we all are.”

Reflecting on the remarkable journey that began decades ago with curiosity and pond scum, Blackburn remarks, “Now that you know the power of curiosity to change the world, how will you make sure the world invests in curiosity for the sake of the generations that will come after us?”

TED2017 TED会议现场直播
衰老之谜:伊丽莎白布莱克本在 TED2017 演讲
发布者:Rebekah Barnett 2017 年 4 月 27 日美国东部时间晚上 9:09

诺贝尔奖获得者生物学家伊丽莎白布莱克本研究人类如何衰老——以及可能解释年龄如何影响不同人的差异的隐藏因素。她于 2017 年 4 月 27 日在加拿大不列颠哥伦比亚省温哥华举行的 TED2017 演讲。照片:布雷特哈特曼 / TED


端粒是染色体末端非编码 DNA 的特殊部分,就像鞋带末端的塑料尖端一样,在细胞分裂过程中保护我们的编码 DNA。每次细胞分裂时,都必须复制其所有遗传信息,但由于 DNA 复制方式出现故障,端粒会磨损和缩短。端粒通过牺牲自身来帮助保护我们的编码 DNA 在细胞分裂过程中不被磨损。最终,磨损的端粒向细胞发出信号,表明编码 DNA 处于危险之中,细胞是时候死亡了。基于这项研究,布莱克本得出结论,端粒缩短只是衰老的一个事实,但事实证明这远非全部。

与同事 Carol Greider 一起,她注意到了一些奇怪的事情。池塘浮渣细胞永远不会变老和死亡。 “随着时间的推移,它们的端粒并没有缩短。有时它们甚至会变得更长,”她说。 “还有其他事情在起作用。”

这个谜团让他们发现了一种以前做梦都想不到的酶——端粒酶,它有助于补充端粒。 “当我们去除池塘浮渣中的端粒酶时,它们的细胞会磨损并死亡,”她说。换句话说,端粒酶可以减缓、防止甚至逆转由细胞分裂引起的端粒缩短,并且正如我们将看到的那样,生活压力会加剧端粒缩短。




布莱克本开始怀疑我们是否可以控制我们的端粒长度——以及我们的健康和幸福。当心理学家 Elissa Epel 走进她的实验室时,答案就来了。 Appel 研究了严重的慢性心理压力的影响,重点关注患有慢性疾病的儿童的照顾者,她想知道长期压力下的端粒发生了什么变化。


阿佩尔和布莱克本共同对一组照顾母亲进行了他们的第一项研究。结果出来后,阿佩尔倒吸一口凉气。 “有一种模式,”布莱克本回忆道。 “这是我们最担心可能存在的确切梯度。”母亲照顾人的时间越长,端粒越短,母亲越觉得自己的处境压力大,端粒酶越低,端粒越短。

然而,“隐藏在这些数据中的是希望,”布莱克本说。一小群母亲尽管照顾了自己的孩子多年,但仍设法维持了端粒。 “他们能够承受压力,”她解释道。他们发现了母亲对压力的反应方式的不同。具有弹性端粒的母亲不会将压力视为威胁,而是将其视为挑战。 “人们的生活事件以及他们对这些事件的反应方式会影响他们维持端粒的方式,”布莱克本解释道。

其他科学家对布莱克本和阿佩尔的研究很感兴趣,也开始探索端粒的奥秘。结果令人惊讶。在一项研究中,研究人员发现,在两个月内每天练习 12 分钟冥想的痴呆症亲属的照顾者的端粒酶增加了 43%。其他人发现,童年时期的情感忽视、暴力暴露、欺凌和种族主义都会对端粒产生长期影响。相比之下,紧密的社区、终生的友谊和长期的婚姻可以保护他们。

“我有能力影响我自己端粒,我也有能力影响你的,”布莱克本说。 “端粒科学告诉我们,我们是多么相互关联。”

布莱克本回顾了几十年前始于好奇心和池塘渣滓的非凡旅程,他说:“既然你知道好奇心改变世界的力量,你将如何确保世界为了后代而投资于好奇心。 来找我们?”

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