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

譯者: Aaron Shoo 審譯者: Yamei Huang

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

這是幅 16 世紀的畫作， 繪者是老盧卡斯·克拉納赫。

It shows the famous Fountain of Youth.

畫的是有名的「青春之泉」。

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

如果喝了泉水或是沐浴其中， 就會變得健康、年輕。

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

每種文化、每個文明， 都夢想能夠青春永駐。

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

亞歷山大大帝 或是探險家龐塞德萊昂，

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

終其一生追尋不老之泉。

They didn't find it.

最後無疾而終。

But what if there was something to it?

但它真的存在嗎？

What if there was something to this Fountain of Youth?

青春之泉會不會是真的？

I will share an absolutely amazing development in aging research

我要分享「老化研究」的驚人發展，

that could revolutionize the way we think about aging

徹底顛覆我們對老化的了解，

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

以及未來老年疾病的治療。

It started with experiments that showed,

首先是一些實驗顯示，

in a recent number of studies about growing,

近期關於「成長」的研究指出，

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

動物，比如年老的老鼠， 被供應年輕老鼠的血液，

can get rejuvenated.

會變年輕。

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

這個情況就像人類的連體嬰，

and I know this sounds a bit creepy.

雖然聽起來有點詭異。

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

但根據幹細胞研究員 湯姆‧蘭朵 2007 年的報告，

was that old muscle from a mouse can be rejuvenated

老鼠的老肌肉可以年輕化

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

藉由暴露在年輕的血液循環系統。

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

幾年後艾美‧維潔 在哈佛重做這個實驗，

and others then showed that similar rejuvenating effects could be observed

結果發現類似的年輕化效果，

in the pancreas, the liver and the heart.

也發生在胰臟、肝臟、心臟。

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

但最令我和其他同業興奮的是，

is that this may even apply to the brain.

這也可能發生在大腦。

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

我們發現老老鼠 被暴露在年輕的環境中，

in this model called parabiosis,

也就是模型中的「連體鼠」，

shows a younger brain --

有更年輕的腦、

and a brain that functions better.

運作得更好的腦。

And I repeat:

再重說一次：

an old mouse that gets young blood through shared circulation

藉由共享循環系統 獲得年輕血液的老老鼠，

looks younger and functions younger in its brain.

腦部看起來、也運作得更年輕。

So when we get older --

所以當我們老去，

we can look at different aspects of human cognition,

用不同面向分析人類的知覺，

and you can see on this slide here,

如這張投影片所示，

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

比如推理、言語或其他能力。

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

到了 50 或 60 歲， 這些功能都還正常，

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

告訴在座各位「年輕朋友」： 我們還算硬朗。

(Laughter)

(笑聲)

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

但可怕的是， 這些線會持續下滑。

And as we get older,

隨著年紀漸長，

diseases such as Alzheimer's and others may develop.

阿茲海默症之類的病就可能併發。

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

大家都知道隨著老化， 神經元之間的連結，

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

它們之間的溝通方式， 也就是「突觸」開始退化；

neurons die, the brain starts to shrink,

神經元死亡、大腦開始萎縮，

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

增加罹患神經組織退化疾病的風險。

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

這裡有個大問題， 當我們想了解大腦

at a very molecular mechanistic level --

分子、機轉層面的運作，

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

沒辦法在活人身上研究。

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

我們可以做知覺測試、掃描，

all kinds of sophisticated testing.

各種精細的檢查。

But we usually have to wait until the person dies

但通常要等到人死後，

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

剖析腦的內部， 才知道老化或疾病造成的改變。

This is what neuropathologists do, for example.

這是神經病理學家其中一項工作。

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

假設腦只是大型有機體的一部份。

Could we potentially understand more

我們有沒有可能，

about what happens in the brain at the molecular level

從分子的角度更了解大腦運作，

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

只把腦當作身體的某個部分？

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

如果身體老化或生病， 會影響到大腦嗎？

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

或相反，當腦老化， 會不會影響身體其他部位？

And what connects all the different tissues in the body

而連結身體各不同組織的

is blood.

就是「血液」。

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

血液不只是夾帶輸氧細胞的組織，

the red blood cells,

例如紅血球，

or fights infectious diseases,

或是抵抗傳染病，

but it also carries messenger molecules,

同時也夾帶了訊息因子，

hormone-like factors that transport information

像賀爾蒙的因子，傳遞訊息，

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

從一個細胞到另一個細胞， 一個組織到另一個組織，

including the brain.

在大腦裡也一樣。

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

所以我們看血液 因為疾病或老化產生的改變，

can we learn something about the brain?

會不會更認識大腦？

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

我們知道隨著年紀漸長， 血液也會改變，

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

這些像賀爾蒙的因子也會改變。

And by and large, factors that we know are required

目前我們所知，

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

發展或是維持組織 所需的因子或多或少，

they start to decrease as we get older,

隨著年齡增長而減少，

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

會造成破損、受傷、發炎的因子，

they increase as we get older.

卻隨著年齡增長而增加。

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

所以說起來， 好因子和壞因子之間失衡了。

And to illustrate what we can do potentially with that,

為了說明怎麼改善這個情況，

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

我想解釋一下我們之前的實驗。

We had almost 300 blood samples from healthy human beings

我們取了 300 份 健康人類的血液樣本，

20 to 89 years of age,

從 20 歲到 89 歲都有，

and we measured over 100 of these communication factors,

測試了超過 100 種這些溝通因子，

these hormone-like proteins that transport information between tissues.

這些像賀爾蒙在組織間 傳遞訊息的蛋白質。

And what we noticed first

我們首先發現

is that between the youngest and the oldest group,

在最年輕和最年老的樣本間，

about half the factors changed significantly.

有半數左右的因子有顯著改變。

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

所以我們的身體在老化以後， 對這些因子來說，

when it comes to these factors.

是一個非常不一樣的環境。

And using statistical or bioinformatics programs,

藉由這些統計、生物信息資料，

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

我們可以試著去發現 最能預測年齡的因子，

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

也就是反推某個人的相對年齡。

And the way this looks is shown in this graph.

如同這張圖所顯示。

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

橫軸是人的實際年齡，

the chronological age.

也就是年齡序列。

So, how many years they lived.

看他們實際活了多久。

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

然後我們用剛剛的重要因子，

and we calculate their relative age, their biological age.

去計算縱軸的相對、生理的年齡。

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

你會發現兩者高度相關，

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

所以能預測人的相對年齡。

But what's really exciting are the outliers,

但偏離線外的點更值得注意，

as they so often are in life.

他們不算少數。

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

你看綠點標記的這個人，

is about 70 years of age

將近 70 歲左右，

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

但他的生理年齡， 如果我們的推論正確，

of only about 45.

只有大概 45 歲。

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

所以這個人是不是 實際看起來更年輕？

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

更重要的是： 這個人是不是罹患

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

老化疾病的風險更小， 也會更長壽？

will live to 100 or more?

甚至超過 100 歲？

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

另一方面， 紅點標記的這位，

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

還不到 40 歲， 但生理年齡已經 65 歲。

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

罹患老化疾病的風險是不是更高？

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

所以我們實驗室 試著更了解這些因子，

and many other groups are trying to understand,

其他團隊也在努力，

what are the true aging factors,

關鍵的老化因子是什麼？

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

我們找出來以後， 能不能有效預測老化疾病？

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

我剛剛說的 只是簡單的關聯性，

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

你可能會說： 「這些因子會隨年齡改變嘛。」

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

但怎麼知道不是因子改變年齡？

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

所以我現在再說一個關鍵，

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

說明這些因子會改變組織的年齡。

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

回到剛剛的「連體鼠」實驗。

So, parabiosis is done in mice

這是將兩隻老鼠，

by surgically connecting the two mice together,

用手術連接在一起，

and that leads then to a shared blood system,

共享同一個血液循環系統，

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

所以我們會問： 「比較老的腦接觸到年輕血液

by exposure to the young blood?"

會有什麼影響？」

And for this purpose, we use young mice

所以我們找了一隻小老鼠，

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

換算大約是人類的 20 歲，

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

和大約人類 65 歲的老老鼠。

What we found is quite remarkable.

有個非常驚人的發現。

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

我們發現產出更多神經幹細胞 製造新的神經元

in these old brains.

在這些老的大腦裏面。

There's an increased activity of the synapses,

突觸的活動變得更活躍，

the connections between neurons.

突觸是神經元之間的連結。

There are more genes expressed that are known to be involved

大家所知 更多的基因顯示涉及

in the formation of new memories.

新記憶的資訊。

And there's less of this bad inflammation.

導致發炎的壞因子減少。

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

我們也觀察到， 沒有新的細胞進入大腦。

So when we connect them,

也就是說這個實驗中，

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

沒有任何細胞進入老腦。

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

所以可以推論， 這些因子一定溶於血，

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

所以我們只需要收集 血液裡的血漿，

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

然後把老血漿或年經血漿 注入老鼠體內，

and we could reproduce these rejuvenating effects,

就可以重現年輕化的效果，

but what we could also do now

但在此同時我們也可以，

is we could do memory tests with mice.

幫老鼠做記憶測試。

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

老鼠老了就跟人一樣， 記憶力會衰退。

It's just harder to detect them,

雖然不容易觀察，

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

但我等一下會說我們怎麼做。

But we wanted to take this one step further,

我們還想更進一步，

one step closer to potentially being relevant to humans.

更近一步把結果和人類做連結。

What I'm showing you now are unpublished studies,

接下來要說的實驗還沒發表，

where we used human plasma, young human plasma,

我們用年輕人類的血漿，

and as a control, saline,

和生理食鹽水做對照，

and injected it into old mice,

注入到老老鼠體內，

and asked, can we again rejuvenate these old mice?

想知道 能不能再次年輕化老老鼠？

Can we make them smarter?

能讓牠們變聰明嗎？

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

我們用「巴恩斯迷宮」來測試。

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

這張大桌子有很多洞，

and there are guide marks around it,

上面有一些指示標記，

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

像這個講台一樣有打光。

The mice hate this and they try to escape,

老鼠討厭光所以想逃跑，

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

要找到箭頭指的這個洞，

where a tube is mounted underneath

底下接了一根管子，

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

牠們可以藉此重返舒適的黑洞。

So we teach them, over several days,

所以我們教了牠們幾天，

to find this space on these cues in the space,

怎樣透過標記找到小黑洞，

and you can compare this for humans,

拿人類來說，

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

就像逛了賣場一整天， 最後要在停車場找車。

(Laughter)

(笑聲)

Many of us have probably had some problems with that.

很多人都覺得那是大挑戰。

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

回來看這隻老老鼠。

This is an old mouse that has memory problems,

這是隻記憶力不好的老老鼠，

as you'll notice in a moment.

你等一下就知道了。

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

牠每個洞都看， 但對空間毫無頭緒，

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

對之前走過的路， 或昨天的事完全沒有印象。

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

這邊的對照組 是牠同齡的手足，

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

但已經連續接受人類血漿 3 週，

with small injections every three days.

每 3 天一次的少量施打。

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

你會發現牠環顧四周說： 「這是哪？」

and then walks straight to that hole and escapes.

接著直直走到那個洞離開。

So, it could remember where that hole was.

顯然牠記得洞的位置。

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

看來這隻老老鼠年輕化了，

it functions more like a younger mouse.

活得比較像一隻年輕老鼠。

And it also suggests that there is something

代表不只是

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

年輕老鼠的血漿裡面， 年輕人類的血漿裡，

that has the capacity to help this old brain.

也有能改善大腦能力的因子。

So to summarize,

結論就是，

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

我們發現老老鼠， 特別是大腦，是具可塑性的。

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

決不是一成不變， 而是可以被我們改造。

It can be rejuvenated.

可以被年輕化。

Young blood factors can reverse aging,

年輕的血液因子讓你返老還童，

and what I didn't show you --

但我沒說的是，

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

實驗裡的年輕老鼠， 卻因此被拖累。

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

所以年老血液的因子會加速老化。

And most importantly, humans may have similar factors,

更重要的是， 人類也有類似的因子，

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

因為用年輕人血做實驗 也有類似效果。

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

但是老年人的血液 在實驗裡卻無效，

it does not make the mice younger.

沒有讓老鼠變年輕。

So, is this magic transferable to humans?

所以這能不能套用到人類呢？

We're running a small clinical study at Stanford,

我們在史丹佛做小型的臨床實驗，

where we treat Alzheimer's patients with mild disease

對輕度阿茲海默症患者，

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

施打 1 品脫 20 歲志願者的血漿，

and do this once a week for four weeks,

每週一次連續 4 週，

and then we look at their brains with imaging.

然後再用儀器掃描他們的腦、

We test them cognitively,

測試他們的知覺，

and we ask their caregivers for daily activities of living.

透過照護員了解日常活動。

What we hope is that there are some signs of improvement

我們希望透過這種治療，

from this treatment.

看到一些好轉的跡象。

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

如果成功，我們會希望

that what I showed you works in mice

老鼠實驗展現的成果，

might also work in humans.

也會在人類身上實現。

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

我不認為人會長生不死。

But maybe we discovered

但也許我們發現，

that the Fountain of Youth is actually within us,

青春之泉就在我們身體裡，

and it has just dried out.

只是逐漸乾涸。

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

如果能稍微活化它，

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

找到讓我們年輕化的因子，

we can produce these factors synthetically

想辦法合成這些因子，

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

就可以治療老化疾病，

or other dementias.

例如阿茲海默或其他失智。

Thank you very much.

非常感謝。

(Applause)

(掌聲)