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人类能成功战胜衰老吗?与自然规律的博弈在继续

更新时间:2019/1/21 21:05:05 来源:纽约时报中文网 作者:佚名

Can we cheat ageing?
人类能成功战胜衰老吗?与自然规律的博弈在继续

As she headed to her lab one sunny Texan morning, molecular biologist Meng Wang couldn’t yet guess what would be waiting for her when she arrived: tens of thousands of worms, wriggling around in different boxes. As she peered into each box, slowly it dawned on her. What she saw could cure the most debilitating condition known to humanity: ageing.

在德克萨斯州一个阳光明媚的早晨,分子生物学家王濛(音)正在朝实验室走去。她猜都猜不到抵达实验室后,等着自己的是什么:数万只蠕虫被装在不同的盒子里,不停地蠕动着。她仔细地观察每只盒子里的蠕虫,过了一会恍然大悟,她观察到的现象兴许可以治愈人类无可挽回的变弱症状:衰老。

Diseases related to ageing – like cancer, rheumatism and Alzheimer’s – kill 100,000 people every day around the world. But a growing number of scientists say it doesn’t have to be this way.

全球每天有10万人死于与衰老有关的疾病,比如癌症、风湿和阿尔茨海默氏症。但越来越多的科学家表示,情况不一定非得如此。

BBC World Service podcast The Inquiry quizzed some of the world’s leading researchers about the nature of ageing – and about the cutting-edge science that could ‘cure’ it, from the role of microbiomes to 3D-printed organs.

BBC国际频道(BBC World Service)的播客频道调查(The Inquiry)采访了部分世界顶级科学家,向他们请教了有关衰老的本质,以及可能"治愈"衰老的前沿科学,如微生物群的作用到3D打印器官技术等。

Long tooth

衰老

What exactly is ageing? If you could zoom into the molecular level, you would see small, incremental amounts of damage that spreads to the cells, the tissue and the organs. Eventually, the whole organism starts to suffer from this ongoing Russian-doll style accumulation of damage.

衰老究竟是什么?如果能放大观看到人体分子这个层次,你会看到微小但量会持续增加的损伤在细胞、组织和器官中不断扩大。这种损伤持续积累,像俄罗斯套娃似的相互嵌套一样,最后影响到整个人体机能。

“Then when we can’t keep up with the repairing, the ageing starts” explains Danish physician Kaare Christensen.

丹麦医生克里斯滕森(Kaare Christensen)解释说,"当我们身体的修复跟不上损伤的时候,衰老就开始了。"

Christensen worked as a doctor for many years until one day he decided he’d had enough of treating sick people. He now runs the Danish Aging Research Centre where he’s trying to stop people getting ill in the first place.

克里斯腾森从医多年,直到有一天他觉得自己受够了治疗病人的工作。现在,他是丹麦衰老研究中心(Danish Aging Research Centre)的负责人。在那里,他试图让人们首先做到不会患病。

He points out that we’ve seen some progress. In the mid-1800s life expectancy was around 40 years in most of the world, he says, while now some countries of Northern Europe are nearing 80 years and the rest of the planet is catching up.

他指出,我们已经看到了一些进展。他说, 19世纪中期世界大部分地区的预期寿命约为40岁,但现在北欧一些国家已接近80岁,世界其他地区也正在迎头赶上。

This was largely because of the reduction in infant and child mortality, not because the human life span itself increased. (Find out more in our recent story: Do we really live longer than our ancestors?).

这主要是因为婴儿和儿童死亡率降低,而非人类寿命本身增加了。

Even so, there has been another, promising change at the same time.

即便如此,同时也出现了另一个前景光明的变化。

“People arrive at higher ages in better shape now,” says Christensen. “One easy thing to observe is, for instance, teeth. You can see that the teeth of elderly people are getting better and better for every decade.”

克里斯腾森说,"老年人的身体状态比以前好。比如说,一个容易观察到方面是牙齿。你会发现,以十年为间隔,老年人的牙齿变得越来越好。"

Teeth are a sort of barometer of general health, he says. Their condition directly affects our ability to eat properly and gain nourishment. Their fitness can also indicate whether other parts of the body are in good shape.

他说,牙齿是整体健康情况的一种标志。牙齿情况直接影响我们正常进食和获取营养的能力。牙齿的健康状况也能表明身体其他部位是否状态良好。

Christensen says that people are not only reaching old age with better teeth, but also with higher results in IQ tests, which he links to improved livelihoods around the world.

克里斯滕森说,老年人不仅牙齿比以前好,智商测试成绩也有提高。他认为这和全球生活水平改善有关。

“That’s the whole package of better living conditions, better schooling… and what kind of work you have had,” he says.

他说,"原因包括生活条件改善、教育水平提升……以及早前从事的工作性质。"

He believes that this progress will continue. But for how long?

他认为这种进展趋势会持续下去。但会持续多久呢?

The record for the world’s longest recorded lifespan currently belongs to Frenchwoman Jeanne Louise Calment, who reached 122 years of age. What’s interesting is that she died in 1997 – more than 20 years ago. Many things have happened since.

目前全世界最长寿记录的保持者是法国人让娜·路易斯·卡尔芒(Jeanne Louise Calment)。她活了122岁。有意思的是,她在20多年前的1997年去世。在那之后,又发生了很多事情。

Organ printing

器官打印

Biophysicist Tuhin Bhowmick comes from a family of medics in Bangalore, India, and remembers dinner conversations about patients his father or uncles could not save. Whenever he asked why they were not able to prevent a death, his father would reply they had run out of tricks up their sleeve. Medicine, after all, had its limits.

生物物理学家布豪米克(Tuhin Bhowmick)出生于印度班加罗尔的一个医生家族。他还记得常在饭桌上谈论到他父亲或叔伯无力挽救的病人。每当他问他们为什么无法阻止死神时,他父亲都会回答说他们已经尽了力。毕竟,医学有自己的局限。

“I was like, ‘Okay, then I won't become a doctor, but I'll become somebody who makes the medicine’,” remembers Bhowmick.

布豪米克回忆说,"我当时想,'好吧,那我以后不当医生了,我要成为一个研发药品的人。"

He says death by old age often relates to malfunctions with vital organs like the heart, the lungs or the liver. If the patient is able to receive a functional organ from a donor, medics like Bhowmick’s father can give people a second lease of life. But that’s not always the case.

他说,衰老导致的死亡通常与重要器官,比如心脏、肺和肝脏的机能衰竭有关。如果病人能够从捐献者那里得到一个机能正常的器官,像布豪米克的父亲这样的医生就能让他们重获新生。但情况并非总是如此。

The problem is that there are more people in need of organs than donors able to give them. Elderly people all over the world are in long queues for new kidneys or hearts, but exact matches have to be found. In many cases, the person dies waiting.

其中的问题在于,需要器官的人比能够捐献器官的人多。全世界等着换肾或心脏的老年人排起了长队,但必须找到完全匹配的器官。很多情况下,人们未等到换器官已离世。

Instead of holding out for a donor organ, Bhowmick thought, what if you could make one? This question kickstarted his quest to print a functioning organ that patients’ bodies would not reject.

布豪米克想,如果不是坐等他人捐献器官,而是可以打造人体器官会怎样?这个问题促使他开始探索如何打印出机能正常且不会被病人身体排斥的器官。

“Let's say you need a liver and you have CT scan or you have MRI which shows exact size and shape of your organ in the computer,” he says. You could feed that ‘mould’ to a 3D printer and print an artificial one in exactly the same size and shape.

他说,"假设你需要换肝,你做了电脑断层扫描,或做了核磁共振成像,电脑上会显示出你肝脏的具体大小和形状。"你可以把"模具"放入3D打印机,然后打印出一颗尺寸和形状一模一样的人工肝脏。

Instead of using an ink cartridge, though, Bhowmick’s devices use ink made up of protein and cells – and not just any cells, but the patient’s own cells.  This means there is very little chance that the body would reject the new organ.

但布豪米克需要的打印材料不是墨盒,而是由蛋白质和细胞组成的材料,并且不是任意细胞,而是病人自己的细胞。这意味着其身体排斥新器官的可能性微乎其微。

His team already has made India’s first artificial human liver tissue; the next step is to scale it up, making a miniature external liver, a checkpoint that he estimates might be five years away. Bhowmick imagines this external organ as a small and portable out-of-the-body device, so users can move around with it.

他的团队已经制造出印度第一个人造人类肝脏组织,下一步是扩大规模,制造一颗微型外置肝脏。他估计这可能需要五年时间。布豪米克把这个外置器官想象成一个小型的便携式体外设备,这样使用者便可随身携带。

In eight to 10 years, he expects to reach the promised land: a point where he can make a fully functioning liver that can be transplanted inside a body.

他预计8到10年内便会实现理想的最终愿景:制造一颗功能完备,可移植到人体体内的肝脏。

But if a person has got a failing organ, does that indicate that perhaps they're coming to the end of a natural lifespan? What if the heart and lungs also fail?

但如果一个人的某个器官日渐衰竭,这是否预示着他们的自然寿命可能即将终结呢?如果心脏和肺也一道衰竭了呢?

Bhowmick believes each case is different.

布豪米克认为,每一种情况都有所不同。

“If you replace an organ which has been the primary cause of the patient's death, that patient could have lived for 20 more years because maybe that person's liver was failing, but not the same with the brain or the heart,” he says.

他说,"如果某个器官是病人死亡的主要原因,而你把它换掉了,那这个病人可能会多活20多年,因为可能这个病人的肝脏衰竭了,但他的大脑或心脏还没有到这地步。"

His bet for how long we can live? With these types of innovations, he says, if you are a millennial or younger – born by 1981 or later – you could have a good shot at lifespan of 135 years.

布豪米克认为我们能活多久呢?他说,有了这些创新,如果你是千禧一代或者更年轻,即1981年前后出生的人,你很可能会活到135岁。

Worm wisdom

蠕虫智慧

Meng Wang’s grandmother passed away when she was aged 100; she was healthy and active to the end of her life. Watching her grow older, all while remaining sound, made Wang wonder about the secrets of ageing.

王濛的祖母去世时100岁。老人一直健康、活跃,直到生命的尽头。看着祖母慢慢变老却依然身体硬朗,王濛不禁琢磨起了衰老的秘密。

Wang is now a professor of molecular and human genetics at Baylor College of Medicine in the US, where she’s been carrying out experiments into one of the most exciting new areas of medicine – our microbiome.

王濛现在是美国贝勒医学院(Baylor College of Medicine)的分子和人类遗传学教授。她一直在用实验的方式研究最令人兴奋的新兴医学领域之一——人体的微生物群。

“Those are the little microorganisms living together with us, from the digestive tract inside our body to the skin outside our body,” she says. “So, they’re everywhere.”

她说,"那些就是和我们共处的小微生物,从我们体内的消化道到体外的皮肤,可说无处不在。"

You can’t see it with the naked eye, but our microbiome is all over (and inside of) us. Most of it is bacteria, but it also contains fungi, viruses and other microbes, too. In the past, scientists haven’t given it much attention. But we now know it has a profound effect on our body.

用肉眼看不到微生物,但却遍布我们全身,从体外到体内。依附人体的大部分微生物群是细菌,但也有真菌、病毒和其他微生物。过去,科学家不太关注人体微生物群。但现在我们知道,这些看不见的微生物对我们的身体影响深远。

Recent studies show that our microbiome is as relevant to us as an additional organ might be. It can influence how we behave and even how well we respond to different medications.

最近的研究表明,微生物群之于我们的重要性堪比人体一个新器官,可能会影响我们的行为方式,甚至我们对不同药物的反应。

“Sometimes [our microbiomes] make us sick, but on the other hand, they also play a very important role to keep us healthy,” says Wang.

王濛说,"有时候,人体微生物群会导致我们患病,但另一方面,在保持我们身体健康方面也起着非常重要的作用。"

She wanted to know whether our microbiome could affect ageing. To test it, she decided to work with a particular kind of worm that lives only two to three weeks – a lifespan short enough to conduct a ‘life-long experiment’ on ageing. Her question was what would happen if you altered a worm’s microbiome. Would the worm live longer?

她想知道微生物群是否会影响衰老。为了验证这一点,她决定研究一种只能活两到三周的蠕虫来做实验。因为这种蠕虫的寿命足够短,适合用来对衰老进行"终生实验"。她要解决的问题是,如果改变蠕虫的微生物群,情况会怎样?蠕虫会活得久一些吗?

Wang chose one of the kinds of bacteria that lives inside a worm’s gut, tweaked its genes to make different varieties, and then fed the bacteria to separate groups of worms. Three weeks later – by the time they should have all died – she checked on them.

王濛选择了一种生活在蠕虫内脏里的细菌,然后对细菌的基因做了微调,以便制造出不同的种类,再把细菌喂给不同的蠕虫组。三周后她去检查这些蠕虫,按期生命周期蠕虫这时应该都死了。

“I was so excited because we found in a few cases the animals were not dead,” she remembers. “They were still alive when we checked them.

她回忆说,"我很激动,因为我们发现其中几种,蠕虫没有死,我们检查的时候还活着。"

“I was jumping up and down because it was totally unexpected.”

"我激动得跳上跳下,因为完全出乎意料。"

Older worms usually show a decline in physical activity, but the ones with the new microbiome not only wriggled around more quickly in their old age, but were less susceptible to disease too.

老年的蠕虫通常会表现出体力衰竭,活动减少,但体内有了新的微生物群后,老年蠕虫不仅蠕动速度更快,而且也减少了患病。

Wang is now carrying out tests on mice to see whether changing their microbiome extends their lives in a similar way.

王濛现正在老鼠身上进行试验,看改变老鼠的微生物群是否也会延长它们的寿命。

There’s a chance that one day doctors might be able to prescribe pills which do the same for us. How long could that make us live?

也许有一天,医生能够给我们开具有类似功效的药物。这会让我们活多久呢?

“Some of my colleagues say, ‘Okay, you know, I think people can live to 200, 300 years’,” says Wang. “Personally, I think, you know, 100… is already a good number.”

王濛说,"一些同事说,'好吧,你知道吗,我认为人们能活到两三百岁,'我个人认为,100岁……就已经算不错了。"

Cell-by date

细胞衰老

Something odd happens when you age. As cells gets older, they divide to replace cells that are dying or getting worn out, but this is not a perfect process. The more times a cell divides, the greater it’s chance of becoming what we would call ‘senescent’.

在你衰老的过程中,会发生一种奇怪的事情。细胞会在衰老的过程中分裂,取代即将死亡或日渐衰竭的细胞,但这并不是一个完美的过程。细胞分裂的次数越多,我们所说的"衰老"状态的几率越大。

Senescence comes from the Latin word senescere – to grow old. And that’s exactly what’s happened to these cells – they’ve grown old and come to the end of their lifecycle. But instead of dying, they hang around, acting in a destructive manner and communicating with cells around them. That can cause a lot of trouble.

Senescence(衰老)这个词来自拉丁语中的senescere,正是这些细胞的经历——老化,生命周期终结。但老化的细胞没有死去,而是四处游荡,以一种破坏性的方式活动,并与周围的细胞交流。这可能会带来很多麻烦。

“It’s almost like the cell saying ‘I’m an old cell and you guys have been around here about the same sort of amount of time as I have, so you must be old too’,” says Lorna Harries, professor of molecular genetics at England’s University of Exeter.

英格兰埃克塞特大学(University of Exeter)的分子遗传学教授哈里斯(Lorna Harries)说,"细胞就像是在说'我是一个老细胞,你们这些家伙在这里的时间和我差不多,所以说你们肯定也老了。"

These senescent cells are almost ‘contaminating’ other cells with age and as we grow older, more and more of our cells become senescent until our body is overwhelmed.

在我们老化的过程中,这些衰老细胞几乎是在"污染"其他细胞。随着我们逐渐老去,越来越多的细胞老化,直到我们的身体不堪重负而崩解。

In her lab, Harries might have found a way to deal with these ageing hooligans. Some time ago, Harries suggested that a new researcher she was working with try putting some chemicals on old skin cells to see what would happen.

在实验室里,哈里斯可能已经找到了一种对付这些老化恶棍的办法。不久前,哈里斯建议与她合作的一名新研究人员尝试在老皮肤细胞上加一些化学物质,看看会发生什么情况。

To test the skin cell’s age when the experiment ran its course, they applied a particular dye that would turn cells blue if they were senescent.

为了测试皮肤细胞在整个实验过程中的年龄,他们使用了一种特殊的染料。如果细胞老化,这种染料会把它们变成蓝色。

“What I was expecting to see is that the cells would be still blue and still looking old,” says Harries. “And actually they weren’t… they had gone back to looking more like young cells.”

哈里斯说。"我以为会看到那些细胞依然是蓝色的,看上去依然是老化细胞,但实际上并不是……它们恢复了,看上去更像年轻细胞。"

She didn’t believe the result, so she asked the student to repeat the experiment. Again and again, she came back with the same result – and again Harries sent her back to redo the process.

她不相信这个结果,于是让这名学生重复这个实验。一次又一次,这名学生得到的结果都一样。哈里斯又再次让她回去重复这个过程。

The researcher repeated it about nine times, Harries recalls. “Finally, I kind of looked at it and thought ‘Actually, maybe you’re onto something here’.”

哈里斯回忆说,那名研究人员重复了大约9次。"最后,我看着它,想'实际上,也许你真的发现了什么'。"

The experiment effectively rejuvenated old cells and turned them into young cells, making hers the first experiment ever to have reversed ageing in human cells. Some think the discovery could be the secret to a much longer life. Harries started receiving phone calls from investors and scientists around the world.

该实验有效地让老细胞恢复了活力,把它们变成了年轻细胞。这让她的实验成了最早的逆转人体细胞老化的实验。有人认为,这一发现可能是延长人类寿命的关键。哈里斯开始接到来自世界各地的投资者和科学家的电话。

But Harries still isn’t very bullish about how long could we live; she believes humans have a natural maximum lifespan. Even so, she hopes her line of research ends up in a new generation of anti-degenerative drugs for things like dementia and cardiovascular disease.

但对于我们能活多久,哈里斯依然不是非常乐观。她认为,人类的自然寿命非常长。即便如此,她希望自己的研究方向最终能带来新一代抗衰老药物,以治疗老年痴呆和心血管病这类老年疾病。

“What I’m hoping is that this will allow us one treatment which will address several of those at once, so that people who would have died early will then go on to live their natural allotted lifespan,” says Harries.

哈里斯说,"我希望这会让我们研究出一种能同时解决多个问题的疗法,这样可能英年早逝的人就能活到自然寿命的限期。"

So back to the question: how long could we live?

再回到之前的问题:我们能活多久?

Perhaps one day we will be able to replace our damaged organs, take supplements that give us a youthful microbiome and stop our cells from ageing.

也许有一天。人类将能够替换受损的器官,服用能永葆青春的微生物补充剂,或可以阻止人体细胞老化的药物。

How many years could all this add on? If we go by Tuhin Bhowmick’s prediction, if you’re a millennial, you may be able to get to 135. And by the time we’re there – in 2116, if you were born in 1981 – who knows what else will be possible?

这一切会让我们的寿命延长多少年呢?按照布豪米克的预测,如果你是千禧一代,你兴许能活到135岁,到那时也就是2116年,如果你出生于1981年的话。谁知道还有其他什么可能呢?

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