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  • 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)

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。

字幕與單字

影片操作 你可以在這邊進行「影片」的調整,以及「字幕」的顯示

B1 中級 中文 美國腔 TED 因子 老鼠 老化 年輕 血液

【TED】Tony Wyss-Coray:年輕的血液可能有助於逆轉衰老。是的,真的(年輕的血液如何幫助逆轉衰老。是的,真的| Tony Wyss-Coray) (【TED】Tony Wyss-Coray: How young blood might help reverse aging. Yes, really (How young blood might help reverse aging. Yes, really | Tony Wyss-Coray))

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    Max Lin   發佈於 2021 年 01 月 14 日