How young blood might help reverse aging. Yes, really | Tony Wyss-Coray

翻译人员: Tian Ye 校对人员: Yolanda Zhang

This is a painting from the 16th century from Lucas Cranach the Elder.

这是一幅16世纪的画作， 作者是老卢卡斯•克拉纳赫，

It shows the famous Fountain of Youth.

描绘的是著名的青春之泉。

If you drink its water or you bathe in it, you will get health and youth.

如果你喝下泉水或者在里面洗澡， 你就会变得健康又年轻。

Every culture, every civilization has dreamed of finding eternal youth.

每一种文化，每一个文明， 都梦想着找到永恒的青春。

There are people like Alexander the Great or Ponce De León, the explorer,

于是就有了这样的人， 比如亚历山大大帝和探险家庞塞•德莱昂，

who spent much of their life chasing the Fountain of Youth.

他们花费了一生中的许多时间 来寻找青春之泉，

They didn't find it.

但是没有找到。

But what if there was something to it?

可是，如果真的有呢？

What if there was something to this Fountain of Youth?

如果真的有这种青春之泉呢？

I will share an absolutely amazing development in aging research

接下来我将与大家分享有关 衰老的研究领域的非凡进展，

that could revolutionize the way we think about aging

我们现在对衰老的看法，

and how we may treat age-related diseases in the future.

以及未来我们如何治疗与衰老有关的疾病， 都可能因此而出现革命性的变化。

It started with experiments that showed,

首先，实验表明——

in a recent number of studies about growing,

这些是大量近期的有关生长的研究——

that animals -- old mice -- that share a blood supply with young mice

动物——老年老鼠—— 与年轻老鼠的血液相通时，

can get rejuvenated.

会变得年轻。

This is similar to what you might see in humans, in Siamese twins,

在人类身上，比如连体双胞胎中， 也可以看到相似的结果。

and I know this sounds a bit creepy.

当然我知道听起来有点吓人，

But what Tom Rando, a stem-cell researcher, reported in 2007,

但是，干细胞研究者汤姆•兰道 在2007年发表的报告表明，

was that old muscle from a mouse can be rejuvenated

老鼠身上的陈年肌肉可以变得年轻，

if it's exposed to young blood through common circulation.

只要将其置于年轻血液之中， 仅仅通过普通的血液循环即可实现。

This was reproduced by Amy Wagers at Harvard a few years later,

几年之后，哈佛大学的艾米•魏杰斯 成功重现了这一实验结果，

and others then showed that similar rejuvenating effects could be observed

而其他人的实验表明，

in the pancreas, the liver and the heart.

在胰、肝和心脏 也可以观察到类似的年轻化效果。

But what I'm most excited about, and several other labs as well,

但最让我，还有其它几个实验室 感到兴奋的地方在于，

is that this may even apply to the brain.

这一效果甚至可能应用于大脑。

So, what we found is that an old mouse exposed to a young environment

因此，我们发现， 将老年老鼠置于年轻环境之中，

in this model called parabiosis,

这一模型被称为连体共生，

shows a younger brain --

它的大脑变得年轻了——

and a brain that functions better.

功能也变得更好。

And I repeat:

我再重复一遍：

an old mouse that gets young blood through shared circulation

一只老年老鼠， 通过共通的血液循环得到年轻血液，

looks younger and functions younger in its brain.

其大脑显得更加年轻， 功能也更年轻化。

So when we get older --

当我们逐渐变老时——

we can look at different aspects of human cognition,

我们可以看看人类认知能力的 不同方面，

and you can see on this slide here,

从这张幻灯片上，

大家可以看到推理、语言能力等等。

we can look at reasoning, verbal ability and so forth.

And up to around age 50 or 60, these functions are all intact,

一直到大约50或60岁， 这些功能都没有受损，

and as I look at the young audience here in the room, we're all still fine.

我看了下坐在这里的年轻观众， 大家都没有问题。

(Laughter)

（笑声）

But it's scary to see how all these curves go south.

但是看到这些曲线 开始下降还是挺吓人的。

And as we get older,

当我们变老时，

diseases such as Alzheimer's and others may develop.

会开始出现像阿尔茨海默症（老年痴呆） 这样的疾病。

We know that with age, the connections between neurons --

我们知道，随着年龄增加， 神经元之间的联系——

the way neurons talk to each other, the synapses -- they start to deteriorate;

神经元之间进行对话的突触—— 开始退化；

neurons die, the brain starts to shrink,

神经元开始衰亡， 大脑逐渐萎缩，

and there's an increased susceptibility for these neurodegenerative diseases.

人们也就越来越容易患上 这些神经退化疾病。

One big problem we have -- to try to understand how this really works

我们面临的一大问题是—— 想要在分子和功能机制层面上

at a very molecular mechanistic level --

搞清楚这个过程是如何发生的——

is that we can't study the brains in detail, in living people.

但我们还无法研究 活体人类大脑活动的细节问题。

We can do cognitive tests, we can do imaging --

我们可以进行认知测试， 可以做成像——

all kinds of sophisticated testing.

各种复杂测试。

But we usually have to wait until the person dies

但通常我们得等到人死亡之后，

to get the brain and look at how it really changed through age or in a disease.

才能看到大脑，才能了解因为年龄或疾病， 它到底发生了什么变化。

This is what neuropathologists do, for example.

这就是神经病理学家的工作。

So, how about we think of the brain as being part of the larger organism.

那么，我们不妨把大脑当做 有机体的一部分。

我们是否可能有更深入的了解，

Could we potentially understand more

about what happens in the brain at the molecular level

从分子层面了解， 大脑内部是怎样运转的，

if we see the brain as part of the entire body?

如果我们把大脑看作整个身体的一部分？

So if the body ages or gets sick, does that affect the brain?

那么如果身体变老或生病了， 会影响到大脑吗？

And vice versa: as the brain gets older, does that influence the rest of the body?

而且反过来：如果大脑变老了， 会影响到身体其它部分吗？

And what connects all the different tissues in the body

而将身体各个不同组织联系到一起的就是：

is blood.

血液。

Blood is the tissue that not only carries cells that transport oxygen, for example,

血液是一种组织， 它不只含有携带氧气的细胞，

the red blood cells,

比如说，红细胞，

or fights infectious diseases,

或对抗感染性疾病的细胞，

but it also carries messenger molecules,

它还含有信使分子，

hormone-like factors that transport information

这些类激素的因子， 能够在细胞之间传递信息，

from one cell to another, from one tissue to another,

还能在身体组织之间传递信息，

including the brain.

其中也包括大脑。

So if we look at how the blood changes in disease or age,

那么如果我们看到了血液 因为疾病或年龄而发生了怎样的变化，

can we learn something about the brain?

我们是否也可以以此来 获得大脑的信息呢？

We know that as we get older, the blood changes as well,

我们知道，随着我们逐渐变老， 血液也在同样变化，

so these hormone-like factors change as we get older.

所以这类激素因子 也随着变老而变化。

And by and large, factors that we know are required

从总体上来说，这些因子，

for the development of tissues, for the maintenance of tissues --

我们已知是组织发育所需的， 维持其功能的因子——

they start to decrease as we get older,

随着我们变老，它们开始变少，

while factors involved in repair, in injury and in inflammation --

而与修复、伤害和炎症有关的 那些因子——

they increase as we get older.

它们随着身体的衰老却在增加。

So there's this unbalance of good and bad factors, if you will.

所以存在着这种好坏因素不平衡的局面。

And to illustrate what we can do potentially with that,

关于针对这种情况我们能做些什么，

我想说一说我们所做的一个实验。

I want to talk you through an experiment that we did.

We had almost 300 blood samples from healthy human beings

我们有近300份健康人类的血液样本，

20 to 89 years of age,

年龄范围在20-89岁，

and we measured over 100 of these communication factors,

我们测量了超过100种的这些通信因子，

these hormone-like proteins that transport information between tissues.

这些可以在组织间 传递信息的激素样蛋白质。

And what we noticed first

我们首先注意到的是，

is that between the youngest and the oldest group,

将最年轻和最老的组相比，

about half the factors changed significantly.

这些因子中有大约一半存在显著变化。

So our body lives in a very different environment as we get older,

所以，随着我们变老， 我们身体所处的环境也发生了极大的改变，

when it comes to these factors.

从这些因子的角度来说。

And using statistical or bioinformatics programs,

使用统计和生物信息程序分析后，

we could try to discover those factors that best predict age --

我们想找出对预测年龄 最有效的那些因子——

in a way, back-calculate the relative age of a person.

想用这种方法来反推一个人的相对年龄。

And the way this looks is shown in this graph.

这张图中显示的就是这个方法。

So, on the one axis you see the actual age a person lived,

可以看到一条轴表示的是一个人的年龄，

实际实龄，

the chronological age.

So, how many years they lived.

也就是生活了多少年。

And then we take these top factors that I showed you,

然后我们选取了 给大家展示过的这些主要因子，

and we calculate their relative age, their biological age.

来计算他们的相对年龄， 生理年龄。

And what you see is that there is a pretty good correlation,

大家可以看到，其中有明显的相关性，

so we can pretty well predict the relative age of a person.

所以我们可以相当准确地 预测一个人的相对年龄。

But what's really exciting are the outliers,

但真正令人激动的是 这些规律之外的数据点，

as they so often are in life.

它们在生命进程中是很常见的。

You can see here, the person I highlighted with the green dot

可以看这儿，我用绿点标出的这个人

is about 70 years of age

大约70岁，

but seems to have a biological age, if what we're doing here is really true,

但看来他的生理年龄， 如果我们得到的结果非常可靠的话，

of only about 45.

才45岁。

So is this a person that actually looks much younger than their age?

那么这个人真的是看起来 比实际年龄年轻不少吗？

But more importantly: Is this a person who is maybe at a reduced risk

但更为重要的问题是：

to develop an age-related disease and will have a long life --

这个人出现与衰老相关的疾病的 风险是否会更低——

will live to 100 or more?

他会活过100岁，甚至更长寿吗？

On the other hand, the person here, highlighted with the red dot,

另一个例子，这个以红点标出的人，

is not even 40, but has a biological age of 65.

还没到40岁， 但是生理年龄为65岁。

Is this a person at an increased risk of developing an age-related disease?

这个人出现与衰老相关的疾病的 风险是否会更高？

So in our lab, we're trying to understand these factors better,

所以我们在实验中努力地去 更充分地了解这些因子，

and many other groups are trying to understand,

还有许多其它团队也在努力去了解，

what are the true aging factors,

哪些才是真正的衰老因子，

and can we learn something about them to possibly predict age-related diseases?

我们是否可以从中发现某些信息， 从而有可能预测衰老相关的疾病？

So what I've shown you so far is simply correlational, right?

所以到现在我所展示的这些 完全是相关联的，对吧？

You can just say, "Well, these factors change with age,"

有人就会说： “这些因子的确会随年龄变化，”

but you don't really know if they do something about aging.

但你并不知道 它们是否会影响衰老过程。

So what I'm going to show you now is very remarkable

那么，我即将展示的内容 会非常不同寻常，

and it suggests that these factors can actually modulate the age of a tissue.

它表明这些因子实际上 可以调节组织的年龄。

And that's where we come back to this model called parabiosis.

这就回到了这个模型， 它叫做连体共生。

So, parabiosis is done in mice

我们已经实现了老鼠的连体共生，

by surgically connecting the two mice together,

就是通过手术将两只老鼠 进行生理上的连通，

and that leads then to a shared blood system,

使它们的血液循环互通，

where we can now ask, "How does the old brain get influenced

这样我们就可以问， “将老年大脑置于年轻血液之中，

by exposure to the young blood?"

它会受到怎样的影响？”

And for this purpose, we use young mice

为了解答这个问题，

that are an equivalency of 20-year-old people,

我们使用了相当于人类20岁的年轻老鼠，

and old mice that are roughly 65 years old in human years.

和大约相当于人类65岁的老年老鼠。

What we found is quite remarkable.

我们的发现相当令人吃惊。

We find there are more neural stem cells that make new neurons

我们发现了更多的神经干细胞，

in these old brains.

在老年大脑中产生了新的神经元。

There's an increased activity of the synapses,

突触的活动也增加了，

the connections between neurons.

神经元通过突触相互联系。

也有了更多的基因表达，

There are more genes expressed that are known to be involved

in the formation of new memories.

我们知道它们与新记忆的形成有关。

And there's less of this bad inflammation.

严重炎症的问题也变少了。

But we observed that there are no cells entering the brains of these animals.

但我们观察到并没有细胞 进入这些动物的大脑，

So when we connect them,

当我们将两只动物连在一起时，

there are actually no cells going into the old brain, in this model.

在这个模型中， 实际并没有细胞进入老年大脑。

Instead, we've reasoned, then, that it must be the soluble factors,

于是，我们推论出， 一定是可溶的因子在作用，

so we could collect simply the soluble fraction of blood which is called plasma,

所以我们只需采集血液中的可溶部分， 就是血浆，

and inject either young plasma or old plasma into these mice,

将年轻或年老的血浆注射入这些小鼠，

and we could reproduce these rejuvenating effects,

我们就可以重现这些年轻化效果，

but what we could also do now

而且我们现在还可以做的是，

is we could do memory tests with mice.

我们可以对小鼠进行记忆测试。

As mice get older, like us humans, they have memory problems.

小鼠变老时，和人类一样， 会出现记忆问题，

It's just harder to detect them,

只是很难检验出来，

but I'll show you in a minute how we do that.

不过我稍后会展示我们是怎么做的。

But we wanted to take this one step further,

我们希望能够再前进一步，

one step closer to potentially being relevant to humans.

希望成果能够实质上与人类联系起来， 希望离这一目标更近。

What I'm showing you now are unpublished studies,

我现在展示的是一些未发表的研究，

where we used human plasma, young human plasma,

其中我们使用了人类血浆， 年轻人的血浆，

and as a control, saline,

而对照组使用生理盐水，

and injected it into old mice,

然后注射入老年老鼠体内，

and asked, can we again rejuvenate these old mice?

我们能再次让这些老鼠变年轻吗？

我们能让它们变聪明吗？

Can we make them smarter?

And to do this, we used a test. It's called a Barnes maze.

为了回答这些问题， 我们进行了巴恩斯迷宫测试。

This is a big table that has lots of holes in it,

这是一张大桌子， 上面有许多孔，

and there are guide marks around it,

周围是指示标记，

and there's a bright light, as on this stage here.

有束强光照在桌上， 就像这个舞台一样。

The mice hate this and they try to escape,

老鼠讨厌强光，于是想办法逃走，

and find the single hole that you see pointed at with an arrow,

然后找到这一个孔， 大家可以看到有个箭头指到这里，

where a tube is mounted underneath

在后面连接有一根管道，

where they can escape and feel comfortable in a dark hole.

老鼠可以逃进这里， 它们喜欢呆在黑暗的洞里。

So we teach them, over several days,

于是我们花了几天时间训练它们，

to find this space on these cues in the space,

来根据这片区域里的这些线索， 找到这个地方。

and you can compare this for humans,

大家可以用这个对比人类的行为，

to finding your car in a parking lot after a busy day of shopping.

就像你从购物中心出来， 想要在停车场里找到自己的车一样。

(Laughter)

（笑声）

Many of us have probably had some problems with that.

我们中有许多人 很可能在这方面都有些问题。

So, let's look at an old mouse here.

让我们来看一看这只老年老鼠。

This is an old mouse that has memory problems,

这只老年老鼠有记忆问题，

as you'll notice in a moment.

大家一会儿就能注意到。

It just looks into every hole, but it didn't form this spacial map

它只是每个孔都看一看， 但无法形成空间地图，

that would remind it where it was in the previous trial or the last day.

否则它就会知道这个孔之前试过， 或前一天试过。

In stark contrast, this mouse here is a sibling of the same age,

形成鲜明对比的是这一只老鼠， 它和前一只是同一胎所生，

but it was treated with young human plasma for three weeks,

但是注射了年轻人类血浆，

with small injections every three days.

每三天进行少量注射，共三个星期。

And as you noticed, it almost looks around, "Where am I?" --

大家可以注意到，它几乎就是四处看看， “我在哪儿呢？”——

and then walks straight to that hole and escapes.

然后直接就奔向那个孔，逃走了。

So, it could remember where that hole was.

所以，它能记住那个孔在哪里。

So by all means, this old mouse seems to be rejuvenated --

所以可以肯定地说， 这只老年老鼠看来是变年轻了——

it functions more like a younger mouse.

它的身体机能更像年轻老鼠。

And it also suggests that there is something

而且还表明， 不仅是在年轻老鼠的血浆里，

not only in young mouse plasma, but in young human plasma

在年轻人类的血浆里，

that has the capacity to help this old brain.

也有这种能够改善衰老的大脑功能的能力。

So to summarize,

总结一下，

我们发现这只老年老鼠， 准确地说是它的大脑，是可以改变的。

we find the old mouse, and its brain in particular, are malleable.

They're not set in stone; we can actually change them.

它并非一成不变， 我们真的可以改变它。

It can be rejuvenated.

它可以变得年轻。

Young blood factors can reverse aging,

年轻血液中的因子可以逆转年龄，

and what I didn't show you --

而我所没有展示的是——

在此模型中， 年轻老鼠实际上也是置于年老环境之中。

in this model, the young mouse actually suffers from exposure to the old.

So there are old-blood factors that can accelerate aging.

所以就存在可以加速衰老的 老年血液因子，

And most importantly, humans may have similar factors,

而最重要的是， 人类可能有同样的因子，

because we can take young human blood and have a similar effect.

因为我们可以采集年轻人的血液， 观察到类似的效应。

Old human blood, I didn't show you, does not have this effect;

老年人的血液，我没有展示， 没有这种效应；

it does not make the mice younger.

它无法让老鼠变得年轻。

So, is this magic transferable to humans?

那么，这种神奇效果可以移植到人类身上吗？

We're running a small clinical study at Stanford,

我们在斯坦福进行了 一个小型的临床研究，

where we treat Alzheimer's patients with mild disease

我们找到一些病症较轻的 阿尔茨海默症病人，

with a pint of plasma from young volunteers, 20-year-olds,

为他们输入20岁年轻志愿者的血浆，

and do this once a week for four weeks,

每周一次，每次一品脱（473毫升）， 连续四周，

and then we look at their brains with imaging.

然后我们观察他们的大脑成像。

We test them cognitively,

我们进行认知测试，

and we ask their caregivers for daily activities of living.

并向护理员了解他们的日常活动，

What we hope is that there are some signs of improvement

我们希望见到的是， 通过此项治疗能够出现

from this treatment.

某些改善的迹象。

And if that's the case, that could give us hope

如果真的是这样的话， 我们就看到了希望，

that what I showed you works in mice

我展示给大家的对老鼠进行的研究，

might also work in humans.

对人类也会有效果。

Now, I don't think we will live forever.

我不认为我们可以长生不老，

But maybe we discovered

但也许我们发现了

that the Fountain of Youth is actually within us,

青春之泉其实就在我们的身体里，

and it has just dried out.

只是干涸了而已。

And if we can turn it back on a little bit,

如果我们可以让它再涌出一点点，

maybe we can find the factors that are mediating these effects,

也许我们就可以找到 能减缓这些（衰老）效应的因子，

we can produce these factors synthetically

我们就可以合成这些因子，

and we can treat diseases of aging, such as Alzheimer's disease

来治疗衰老疾病， 诸如阿尔茨海默症，

or other dementias.

或其它痴呆症。

Thank you very much.

谢谢大家。

(Applause)

（掌声）