ABOUT THE SPEAKER
Cynthia Kenyon - Biochemist, geneticist
When it comes to aging well, having “good genes” (or rather, mutant ones) is key, says Cynthia Kenyon. She unlocked the genetic secret of longevity in roundworms — and now she’s working to do the same for humans.

Why you should listen

Cynthia Kenyon is revolutionizing our understanding of aging. As an expert in biochemistry and biophysics at the University of California at San Francisco, she is particularly interested in the influence that genetics have on age-related diseases (from cancer to heart failure) in living things.

Her biggest breakthrough was figuring out that there’s a “universal hormonal control for aging”: carbohydrate intake, which can have a dramatic effect on how two critical genes behave, reducing insulin production and boosting repair and renovation activities. So far, her theory has proved true for worms, mice, rats, and monkeys — and she suspects it applies to humans, too.

By studying aging, Kenyon believes that she and other scientists (many of whom have successfully duplicated her experiments) will be able to pinpoint the molecules responsible for the onset of age-related diseases in people and prevent them. She’s co-founded a drug-development company called Elixir Pharmaceuticals to do just that.

She says: "The link between aging and age-related disease suggests an entirely new way to combat many diseases all at once; namely, by going after their greatest risk factor: aging itself."

More profile about the speaker
Cynthia Kenyon | Speaker | TED.com
TEDGlobal 2011

Cynthia Kenyon: Experiments that hint of longer lives

辛希亞‧凱尼恩: 為延長壽命提供線索的實驗

Filmed:
1,030,469 views

是什麼在控制衰老? 生化學家辛希亞∙凱尼恩發現了一種簡單的基因變異,可以讓構造簡單的秀麗線蟲(C. elegans)延長一倍的壽命。.這項研究和其它發現,可能表示未來人類真能青春長在。
- Biochemist, geneticist
When it comes to aging well, having “good genes” (or rather, mutant ones) is key, says Cynthia Kenyon. She unlocked the genetic secret of longevity in roundworms — and now she’s working to do the same for humans. Full bio

Double-click the English transcript below to play the video.

00:15
Have you ever wanted to stay young年輕 a little longer
0
0
3000
在座諸位是否曾想過要延長自己的青春
00:18
and put off aging老化?
1
3000
2000
延緩衰老?
00:20
This is a dream夢想 of the ages年齡.
2
5000
3000
這是長久以來的夢想
00:23
But scientists科學家們 have for a long time
3
8000
2000
但科學家長期以來
00:25
thought this just was never going to be possible可能.
4
10000
2000
都認為這個夢想永遠都不會實現
00:27
They thought you just wear穿 out, there's nothing you can do about it --
5
12000
3000
人一定都會老嘛 這是無法改變的事情
00:30
kind of like an old shoe.
6
15000
2000
就像一隻舊鞋
00:32
But if you look in nature性質,
7
17000
2000
但如果你觀察大自然
00:34
you see that different不同 kinds of animals動物
8
19000
2000
會發現不同的動物
00:36
can have really different不同 lifespans壽命.
9
21000
2000
壽命長短大不相同
00:38
Now these animals動物 are different不同 from one another另一個,
10
23000
2000
這些動物之所以不同
00:40
because they have different不同 genes基因.
11
25000
2000
是因為牠們的基因不同
00:42
So that suggests提示
12
27000
2000
可想而知
00:44
that somewhere某處 in these genes基因, somewhere某處 in the DNA脫氧核糖核酸,
13
29000
2000
在這些基因的某處 DNA的某處
00:46
are genes基因 for aging老化,
14
31000
2000
存在著導致衰老的基因
00:48
genes基因 that allow允許 them to have different不同 lifespans壽命.
15
33000
2000
讓不同的動物有不同的壽命
00:50
So if there are genes基因 like that,
16
35000
2000
如果這些基因真的存在
00:52
then you can imagine想像 that,
17
37000
2000
想像一下
00:54
if you could change更改 one of the genes基因 in an experiment實驗,
18
39000
2000
如果你在實驗中改變其中一個基因
00:56
an aging老化 gene基因,
19
41000
2000
一個導致衰老的基因
00:58
maybe you could slow down aging老化 and extend延伸 lifespan壽命.
20
43000
3000
就有可能延緩衰老 延長壽命
01:01
And if you could do that, then you could find the genes基因 for aging老化.
21
46000
3000
如果你能這麼做 就可以找到導致衰老的基因
01:04
And if they exist存在 and you can find them,
22
49000
2000
如果真有這種基因而且又被你找到
01:06
then maybe one could eventually終於 do something about it.
23
51000
3000
也許我們就可以藉此大有一番作為
01:09
So we've我們已經 set out to look for genes基因 that control控制 aging老化.
24
54000
3000
因此我們準備尋找可以控制衰老的基因
01:12
And we didn't study研究 any of these animals動物.
25
57000
3000
我們沒有研究其它動物
01:15
Instead代替, we studied研究 a little, tiny, round回合 worm called C. elegans線蟲,
26
60000
3000
反而研究了又細又小 身體圓圓的秀麗線蟲
01:18
which哪一個 is just about the size尺寸 of a comma逗號 in a sentence句子.
27
63000
3000
牠的尺寸大約只有句子裡的逗點那麼大
01:21
And we were really optimistic樂觀 that we could find something
28
66000
3000
我們非常樂觀地認為可以有新發現
01:24
because there had been a report報告 of a long-lived長壽命 mutant突變體.
29
69000
3000
因為已經有一篇報告紀錄了長壽的突變體
01:27
So we started開始 to change更改 genes基因 at random隨機,
30
72000
2000
我們開始隨意地改變基因
01:29
looking for long-lived長壽命 animals動物.
31
74000
2000
尋找長壽的動物
01:31
And we were very lucky幸運 to find
32
76000
2000
而且非常幸運地發現
01:33
that mutations突變 that damage損傷 one single gene基因 called daf-daf-2
33
78000
4000
如果一個名叫daf-2的基因在突變時被破壞
01:37
doubled翻倍 the lifespan壽命 of the little worm.
34
82000
3000
小蟲的壽命就可以延長一倍
01:40
So you can see in black黑色, after a month --
35
85000
2000
請各位看黑線 一個月後─
01:42
they're very short-lived短命; that's why we like to study研究 them
36
87000
2000
這種蟲的壽命很短 所以適合拿來做研究
01:44
for studies學習 of aging老化 --
37
89000
2000
研究老化現象─
01:46
in black黑色, after a month, the normal正常 worms蠕蟲 are all dead.
38
91000
3000
黑線顯示 一個月後 一般的蟲都死了
01:49
But at that time,
39
94000
2000
但與此同時
01:51
most of the mutant突變體 worms蠕蟲 are still alive.
40
96000
2000
大部分的突變蟲仍然還活著
01:53
And it isn't until直到 twice兩次 as long
41
98000
2000
而且會活多一倍的時間
01:55
that they're all dead.
42
100000
2000
才死去
01:57
And now I want to show顯示 what they actually其實 look like in this movie電影 here.
43
102000
3000
現在我想用這支影片 讓各位看看牠們的廬山真面目
02:00
So the first thing you're going to see
44
105000
2000
首先你會看見
02:02
is the normal正常 worm
45
107000
2000
正常的蟲子
02:04
when it's about college學院 student學生 age年齡 -- a young年輕 adult成人.
46
109000
3000
相當於大學生的年紀 剛成年的年輕人
02:07
It's quite相當 a cute可愛 little fellow同伴.
47
112000
3000
牠還蠻可愛的吧
02:10
And next下一個 you're going to see the long-lived長壽命 mutant突變體 when it's young年輕.
48
115000
3000
然後是年輕時期的長壽突變蟲
02:13
So this animal動物 is going to live生活 twice兩次 as long.
49
118000
2000
這種蟲的壽命多一倍
02:15
Is it miserable? It doesn't seem似乎 to be.
50
120000
2000
牠會精神不振嗎?沒有喔
02:17
It's active活性. You can't tell the difference區別 really.
51
122000
3000
牠很活潑 其實你看不出差別
02:20
And they can be completely全然 fertile --
52
125000
2000
牠們完全有生育能力
02:22
have the same相同 number of progeny子孫 as the normal正常 worms蠕蟲 do.
53
127000
2000
和正常小蟲有相同數量的後代
02:24
Now get out your handkerchiefs手帕 here.
54
129000
2000
現在把手帕準備好
02:26
You're going to see, in just two weeks,
55
131000
2000
你會看到 兩個星期後
02:28
the normal正常 worms蠕蟲 are old.
56
133000
2000
正常的小蟲變老了
02:30
You can see the little head moving移動 down at the bottom底部 there.
57
135000
3000
可以看到頭在下方移動
02:33
But everything else其他 is just lying說謊 there.
58
138000
2000
但其它的部份都沒有生氣
02:35
The animal's動物 clearly明確地 in the nursing看護 home.
59
140000
2000
顯然已經住進療養院了
02:37
And if you look at the tissues組織 of the animal動物, they're starting開始 to deteriorate惡化.
60
142000
3000
如果你觀察牠的組織 會發現組織已經開始退化
02:40
You know, even if you've never seen看到 one of these little C. elegans線蟲 --
61
145000
2000
即使你沒看過秀麗線蟲這種小生物
02:42
which哪一個 probably大概 most of you haven't沒有 seen看到 one --
62
147000
2000
你們大部分應該都沒看過
02:44
you can tell they're old -- isn't that interesting有趣?
63
149000
3000
但還是看得出來牠們老了─很有趣對不對?
02:47
So there's something about aging老化 that's kind of universal普遍.
64
152000
3000
所以衰老的某些特徵其實是所有生物共通的
02:50
And now here is the daf-daf-2 mutant突變體.
65
155000
3000
看看有daf-2突變的蟲
02:53
One gene基因 is changed out of 20,000, and look at it.
66
158000
2000
兩萬個基因中只改變這個基因 你看看
02:55
It's the same相同 age年齡, but it's not in the nursing看護 home;
67
160000
3000
同樣的年紀 但沒有住在療養院裡
02:58
it's going skiing滑雪.
68
163000
3000
牠在滑雪
03:01
This is what's really cool: it's aging老化 more slowly慢慢地.
69
166000
3000
很酷對吧 牠衰老得比較慢
03:04
It takes this worm two days
70
169000
2000
這隻蟲要兩天的時間
03:06
to age年齡 as much as the normal正常 worm ages年齡 in one day.
71
171000
2000
來完成一般蠕蟲一天內衰老的程度
03:08
And when I tell people about this,
72
173000
2000
當我跟別人說這件事的時候
03:10
they tend趨向 to think of maybe an 80 or 90 year-old person
73
175000
4000
他們通常想到的是80或90歲的人
03:14
who looks容貌 really good for being存在 90 or 80.
74
179000
2000
不過是看起來狀況極佳的90或80歲
03:16
But it's really more like this:
75
181000
2000
但其實更準確地講
03:18
let's say you're a 30 year-old guy -- or in your 30s --
76
183000
3000
比如說你是30歲的男性 30幾歲
03:21
and you're a bachelor單身漢 and you're dating約會 people.
77
186000
2000
單身貴族 約會不斷
03:23
And you meet遇到 someone有人 you really like, you get to know her.
78
188000
3000
你遇見你喜歡的對象 想多認識對方
03:26
And you're in a restaurant餐廳, and you say, "Well how old are you?"
79
191000
3000
所以在餐廳裡 你問她:「你今年幾歲?」
03:29
She says, "I'm 60."
80
194000
2000
她說:「我60歲」
03:31
That's what it's like. And you would never know.
81
196000
2000
就是這種情況 你根本看不出來
03:33
You would never know, until直到 she told you.
82
198000
2000
你絕對不會知道 除非她告訴你
03:35
(Laughter笑聲)
83
200000
4000
(笑聲)
03:39
Okay.
84
204000
2000
好吧
03:41
So what is the daf-daf-2 gene基因?
85
206000
2000
daf-2基因到底是什麼呢?
03:43
Well as you know, genes基因, which哪一個 are part部分 of the DNA脫氧核糖核酸,
86
208000
2000
各位應該都知道 基因是DNA的一部分
03:45
they're instructions說明 to make a protein蛋白 that does something.
87
210000
3000
告訴蛋白質應該做什麼
03:48
And the daf-daf-2 gene基因
88
213000
2000
而這個daf-2基因
03:50
encodes編碼 a hormone激素 receptor接收器.
89
215000
2000
控制荷爾蒙接收器
03:52
So what you see in the picture圖片 there
90
217000
2000
這張圖片上你可以看到
03:54
is a cell細胞 with a hormone激素 receptor接收器 in red
91
219000
2000
一個細胞 紅色的是荷爾蒙接收器
03:56
punching沖孔 through通過 the edge邊緣 of the cell細胞.
92
221000
2000
正穿過細胞的邊緣
03:58
So part部分 of it is like a baseball棒球 glove手套.
93
223000
2000
它有一部分像棒球手套一樣
04:00
Part部分 of it's on the outside,
94
225000
2000
這一部分在外面
04:02
and it's catching the hormone激素 as it comes by in green綠色.
95
227000
2000
抓住經過的荷爾蒙 就是綠色的部分
04:04
And the other part部分 is on the inside
96
229000
2000
另一部份在裡面
04:06
where it sends發送 signals信號 into the cell細胞.
97
231000
2000
向細胞發送信號
04:08
Okay, so what is the daf-daf-2 receptor接收器
98
233000
2000
daf-2接收器
04:10
telling告訴 the inside of the cell細胞?
99
235000
2000
到底在向細胞內部發送什麼信號呢?
04:12
I just told you that, if you make a mutation突變 in the daf-daf-2 gene基因 cell細胞,
100
237000
3000
我剛剛說 如果你讓daf-2基因細胞產生突變
04:15
that you get a receptor接收器 that doesn't work as well;
101
240000
2000
讓接收器失效
04:17
the animal動物 lives生活 longer.
102
242000
2000
這隻蟲就可以活比較久
04:19
So that means手段 that the normal正常 function功能 of this hormone激素 receptor接收器
103
244000
3000
表示這種荷爾蒙接收器的正常功能
04:22
is to speed速度 up aging老化.
104
247000
2000
就是加速老化
04:24
That's what that arrow箭頭 means手段.
105
249000
2000
箭頭就是這個意思
04:26
It speeds速度 up aging老化. It makes品牌 it go faster更快.
106
251000
2000
它會加速老化 讓老化更快發生
04:28
So it's like the animal動物 has the grim嚴峻 reaper收割者 inside of itself本身,
107
253000
2000
就好像蟲子體內有個死神一樣
04:30
speeding超速 up aging老化.
108
255000
2000
加快老化
04:32
So this is altogether really, really interesting有趣.
109
257000
3000
所以這一切非常 非常有趣
04:35
It says that aging老化 is subject學科 to control控制 by the genes基因,
110
260000
3000
表示老化是由基因控制
04:38
and specifically特別 by hormones激素.
111
263000
3000
更精確一點是荷爾蒙
04:41
So what kind of hormones激素 are these?
112
266000
2000
那這是哪一類的荷爾蒙呢?
04:43
There's lots of hormones激素. There's testosterone睾酮, adrenalin腎上腺素.
113
268000
2000
荷爾蒙有很多種 睪丸激素 腎上腺素
04:45
You know about a lot of them.
114
270000
2000
還有很多大家都熟知的
04:47
These hormones激素 are similar類似
115
272000
2000
控制老化的荷爾蒙
04:49
to hormones激素 that we have in our bodies身體.
116
274000
2000
和我們體內的荷爾蒙很相似
04:51
The daf-daf-2 hormone激素 receptor接收器
117
276000
2000
daf-2荷爾蒙接收器
04:53
is very similar類似 to the receptor接收器
118
278000
2000
跟其它接收器很像
04:55
for the hormone激素 insulin胰島素 and IGF-IGF-1.
119
280000
3000
尤其是專門感應胰島素和IGF-1的接收器
04:58
Now you've all heard聽說 of at least最小 insulin胰島素.
120
283000
2000
大家應該至少都聽過胰島素
05:00
Insulin胰島素 is a hormone激素 that promotes促進 the uptake攝取 of nutrients營養成分
121
285000
3000
這種荷爾蒙是促進養分吸收的
05:03
into your tissues組織 after you eat a meal膳食.
122
288000
2000
吃完飯後 身體組織就可以吸收養分
05:05
And the hormone激素 IGF-IGF-1 promotes促進 growth發展.
123
290000
3000
IGF-1促進生長
05:08
So these functions功能 were known已知 for these hormones激素 for a long time,
124
293000
3000
這些荷爾蒙的功能是大家長久以來耳熟能詳的
05:11
but our studies學習 suggested建議
125
296000
2000
但是我們的研究指出
05:13
that maybe they had a third第三 function功能 that nobody沒有人 knew知道 about --
126
298000
2000
也許還有不為人知道的第三種功能
05:15
maybe they also affect影響 aging老化.
127
300000
2000
會影響老化
05:17
And it's looking like that's the case案件.
128
302000
2000
我們現在面對的似乎就是這種可能性
05:19
So after we made製作 our discoveries發現 with little C. elegans線蟲,
129
304000
3000
從小線蟲身上有了新發現後
05:22
people who worked工作 on other kinds of animals動物
130
307000
2000
研究其他動物的科學家
05:24
started開始 asking, if we made製作 the same相同 daf-daf-2 mutation突變,
131
309000
3000
開始思考 如果讓相同的daf-2突變
05:27
the hormone激素 receptor接收器 mutation突變, in other animals動物,
132
312000
3000
就是荷爾蒙接收器突變 也在其他動物身上發生
05:30
will they live生活 longer?
133
315000
2000
其他動物也會更長壽嗎?
05:32
And that is the case案件 in flies蒼蠅.
134
317000
2000
蒼蠅的確如此
05:34
If you change更改 this hormone激素 pathway in flies蒼蠅, they live生活 longer.
135
319000
3000
如果改變荷爾蒙接收的路徑 蒼蠅可以活更久
05:37
And also in mice老鼠 -- and mice老鼠 are mammals哺乳動物 like us.
136
322000
3000
老鼠也是 而老鼠跟人一樣是哺乳類
05:40
So it's an ancient pathway,
137
325000
2000
所以接收路徑想必十分古老
05:42
because it must必須 have arisen興起 a long time ago in evolution演化
138
327000
2000
因為一定是在演化早期就發展出來的機制
05:44
such這樣 that it still works作品 in all these animals動物.
139
329000
3000
才會在所有動物身上都有效
05:47
And also, the common共同 precursor先導 also gave rise上升 to people.
140
332000
3000
同樣地 人類也是由相同的祖先演化而來
05:50
So maybe it's working加工 in people the same相同 way.
141
335000
2000
所以也許對人類也有效
05:52
And there are hints提示 of this.
142
337000
2000
我們也的確看到這種跡象
05:54
So for example, there was one study研究 that was doneDONE
143
339000
2000
例如 某項研究的對象
05:56
in a population人口 of Ashkenazi德系 Jews猶太人 in New York紐約 City.
144
341000
3000
是紐約市的阿胥肯納吉猶太人族群
05:59
And just like any population人口,
145
344000
2000
就跟其他人口族群一樣
06:01
most of the people live生活 to be about 70 or 80,
146
346000
3000
大部分人可以活到70或80歲
06:04
but some live生活 to be 90 or 100.
147
349000
2000
但有些可以活到90或100歲
06:06
And what they found發現
148
351000
2000
學者發現
06:08
was that people who lived生活 to 90 or 100
149
353000
3000
那些活到90或100歲的人
06:11
were more likely容易 to have daf-daf-2 mutations突變 --
150
356000
3000
比較可能有daf-2的突變
06:14
that is, changes變化 in the gene基因
151
359000
2000
就是說 基因發生改變
06:16
that encodes編碼 the receptor接收器 for IGF-IGF-1.
152
361000
2000
造成接收IGF-1的不同
06:18
And these changes變化 made製作 the gene基因 not act法案 as well
153
363000
5000
這些改變使基因不產生作用
06:23
as the normal正常 gene基因 would have acted行動.
154
368000
2000
不像一般正常的基因
06:25
It damaged破損 the gene基因.
155
370000
2000
它們破壞了基因
06:27
So those are hints提示
156
372000
2000
這些暗示
06:29
suggesting提示 that humans人類 are susceptible易感
157
374000
2000
表示人類也可能受到影響
06:31
to the effects效果 of the hormones激素 for aging老化.
158
376000
2000
控制老化的荷爾蒙對人類也有效
06:33
So the next下一個 question, of course課程, is:
159
378000
2000
因此更進一步的問題 當然就是
06:35
Is there any effect影響 on age-related年齡相關 disease疾病?
160
380000
3000
它對於與年齡相關的疾病有沒有效用?
06:38
As you age年齡, you're much more likely容易
161
383000
2000
當我們逐漸老化 會更有可能得到
06:40
to get cancer癌症, Alzheimer's老年癡呆症 disease疾病,
162
385000
2000
癌症 阿茲海默症
06:42
heart disease疾病, all sorts排序 of diseases疾病.
163
387000
2000
心臟疾病 或其他各種疾病
06:44
It turns out that these long-lived長壽命 mutants突變體
164
389000
2000
我們發現長壽的突變種
06:46
are more resistant to all these diseases疾病.
165
391000
2000
更有能力對抗這些疾病
06:48
They hardly幾乎不 get cancer癌症,
166
393000
2000
牠們很少得癌症
06:50
and when they do it's not as severe嚴重.
167
395000
2000
即使得了也比較不嚴重
06:52
So it's really interesting有趣, and it makes品牌 sense in a way,
168
397000
2000
這是很有趣的現象 其實也很有道理
06:54
that they're still young年輕,
169
399000
2000
因為牠們還很年輕
06:56
so why would they be getting得到 diseases疾病 of aging老化 until直到 their old?
170
401000
3000
所以當然不會有各種老化的病症
07:00
So it suggests提示
171
405000
2000
這也表示
07:02
that, if we could have a therapeutic治療 or a pill to take
172
407000
3000
如果有某種療法或藥物
07:05
to replicate複製 some of these effects效果 in humans人類,
173
410000
2000
可以複製這些效果到人體上
07:07
maybe we would have a way
174
412000
2000
也許就有辦法
07:09
of combating打擊 lots of different不同 age-related年齡相關 diseases疾病
175
414000
2000
對抗許多與年齡有關的各種疾病
07:11
all at once一旦.
176
416000
2000
一勞永逸
07:13
So how can a hormone激素 ultimately最終 affect影響 the rate of aging老化?
177
418000
2000
那麼 荷爾蒙到底怎麼影響老化的速度呢?
07:15
How could that work?
178
420000
2000
它是如何運作的?
07:17
Well it turns out that in the daf-daf-2 mutants突變體,
179
422000
3000
我們發現在daf-2突變種生物中
07:20
a whole整個 lot of genes基因 are switched交換的 on in the DNA脫氧核糖核酸
180
425000
3000
某個DNA上的許多基因都在運作
07:23
that encode編碼 proteins蛋白質 that protect保護 the cells細胞 and the tissues組織,
181
428000
3000
這個DNA負責控制蛋白質 保護細胞和組織
07:26
and repair修理 damage損傷.
182
431000
2000
修復損傷
07:28
And the way that they're switched交換的 on
183
433000
3000
這些基因的運作
07:31
is by a gene基因 regulator調節器 protein蛋白 called FOXOFOXO.
184
436000
3000
是由控制基因的蛋白質FOXO掌管
07:34
So in a daf-daf-2 mutant突變體 --
185
439000
2000
因此在daf-2突變種中─
07:36
you see that I have the X drawn here through通過 the receptor接收器.
186
441000
2000
這裡可以看到接收器上面打了個叉
07:38
The receptor接收器 isn't working加工 as well.
187
443000
2000
接收器沒有作用
07:40
Under those conditions條件, the FOXOFOXO protein蛋白 in blue藍色
188
445000
3000
在這種環境中 FOXO蛋白質 就是藍色的部分
07:43
has gone走了 into the nucleus --
189
448000
2000
進入了細胞核
07:45
that little compartment隔室 there in the middle中間 of the cell細胞 --
190
450000
2000
就是細胞中心的小空間
07:47
and it's sitting坐在 down on a gene基因 binding捆綁 to it.
191
452000
2000
它留在這裡 帶著一個基因
07:49
You see one gene基因. There are lots of genes基因 actually其實 that bind捆綁 on FOXOFOXO.
192
454000
2000
你只看到一個 其實FOXO上帶著很多基因
07:51
And it's just sitting坐在 on one of them.
193
456000
2000
它只留了一個
07:53
So FOXOFOXO turns on a lot of genes基因.
194
458000
2000
FOXO啟動許多基因的功能
07:55
And the genes基因 it turns on includes包括 antioxidant抗氧化劑 genes基因,
195
460000
3000
包括抗氧化的基因
07:58
genes基因 I call carrot-giver胡蘿蔔送禮者 genes基因,
196
463000
2000
還有我稱為「成人之美」的基因
08:00
whose誰的 protein蛋白 products製品
197
465000
2000
它的蛋白質產出物
08:02
actually其實 help other proteins蛋白質 to function功能 well --
198
467000
2000
可以幫助其他蛋白質維持良好運作
08:04
to fold correctly正確地 and function功能 correctly正確地.
199
469000
2000
正確疊合 正常運作
08:06
And it can also escort護送 them to the garbage垃圾 cans of the cell細胞
200
471000
3000
還可以確保其他蛋白質廢棄後在細胞中被處理掉
08:09
and recycle回收 them if they're damaged破損.
201
474000
2000
或在蛋白質受損時進行回收
08:11
DNA脫氧核糖核酸 repair修理 genes基因
202
476000
2000
修復DNA的基因
08:13
are more active活性 in these animals動物.
203
478000
2000
在這些動物體內比較活躍
08:15
And the immune免疫的 system系統 is more active活性.
204
480000
2000
免疫系統也比較活躍
08:17
And many許多 of these different不同 genes基因, we've我們已經 shown顯示,
205
482000
3000
許多這些不同的基因 已經證實
08:20
actually其實 contribute有助於 to the long lifespan壽命 of the daf-daf-2 mutant突變體.
206
485000
3000
確實造成daf-2變種生物較長的壽命
08:23
So it's really interesting有趣.
207
488000
2000
這是非常有趣的發現
08:25
These animals動物 have within them
208
490000
2000
這些動物體內
08:27
the latent capacity容量 to live生活 much longer than they normally一般 do.
209
492000
3000
潛藏著可以活更久的能力
08:30
They have the ability能力
210
495000
2000
牠們有能力
08:32
to protect保護 themselves他們自己 from many許多 kinds of damage損傷,
211
497000
2000
保護自己免於各種傷害
08:34
which哪一個 we think makes品牌 them live生活 longer.
212
499000
3000
我們認為這是牠們長壽的原因
08:37
So what about the normal正常 worm?
213
502000
2000
那一般正常的蟲子呢?
08:39
Well when the daf-daf-2 receptor接收器 is active活性,
214
504000
3000
當daf-2接收器啟動時
08:42
then it triggers觸發器 a series系列 of events事件
215
507000
2000
會觸發一連串反應
08:44
that prevent避免 FOXOFOXO
216
509000
2000
防止FOXO
08:46
from getting得到 into the nucleus where the DNA脫氧核糖核酸 is.
217
511000
3000
進入細胞核 也就是DNA所在的位置
08:49
So it can't turn the genes基因 on.
218
514000
2000
因此基因不會被啟動
08:51
That's how it works作品. That's why we don't see the long lifespan壽命,
219
516000
2000
這就是它運作的方法 也因此如果要長壽
08:53
until直到 we have the daf-daf-2 mutant突變體.
220
518000
2000
一定要有daf-2的變異
08:55
But what good is this for the worm?
221
520000
2000
但這對蟲子有什麼好處?
08:57
Well we think that insulin胰島素 and IGF-IGF-1 hormones激素
222
522000
3000
如果我們回頭看看胰島素和IGF-1激素
09:00
are hormones激素 that are particularly尤其 active活性
223
525000
2000
這兩種特別活躍的荷爾蒙
09:02
under favorable有利 conditions條件 -- in the good times --
224
527000
2000
在有利的條件下 良好的情況中
09:04
when food餐飲 is plentiful豐富 and there's not a lot of stress強調 in the environment環境.
225
529000
3000
如果食物充足 環境中又沒有太大的壓力時
09:07
Then they promote促進 the uptake攝取 of nutrients營養成分.
226
532000
2000
它們會促進養分的吸收
09:09
You can store商店 the food餐飲, use it for energy能源,
227
534000
3000
儲存食物 轉換成能量
09:12
grow增長, etc等等.
228
537000
2000
幫助生長 等等
09:14
But what we think is that, under conditions條件 of stress強調,
229
539000
3000
但我們考慮的是 如果受到壓力影響
09:17
the levels水平 of these hormones激素 drop下降 --
230
542000
2000
荷爾蒙濃度下降
09:19
for example, having limited有限 food餐飲 supply供應.
231
544000
3000
例如 食物來源不足
09:22
And that, we think,
232
547000
2000
這種情形 我們認為
09:24
is registered註冊 by the animal動物 as a danger危險 signal信號,
233
549000
2000
動物本能地就會將之視為警訊
09:26
a signal信號 that things are not okay
234
551000
2000
提醒牠們情況不對勁
09:28
and that it should roll out its protective保護的 capacity容量.
235
553000
3000
牠應該施展自我保護的能力
09:31
So it activates激活 FOXOFOXO, FOXOFOXO goes to the DNA脫氧核糖核酸,
236
556000
3000
因此FOXO開始運作 對DNA產生作用
09:34
and that triggers觸發器 the expression表達 of these genes基因
237
559000
2000
觸發這些基因表現
09:36
that improves提高 the ability能力 of the cell細胞
238
561000
2000
改善細胞能力
09:38
to protect保護 itself本身 and repair修理 itself本身.
239
563000
2000
更能自我保護與修復
09:40
And that's why we think the animals動物 live生活 longer.
240
565000
2000
我們認為 動物因此能活更久
09:42
So you can think of FOXOFOXO
241
567000
2000
所以 你可以把FOXO
09:44
as being存在 like a building建造 superintendent所長.
242
569000
3000
當成大樓的管理員
09:47
So maybe he's a little bit lazy,
243
572000
2000
也許這位管理員有點懶惰
09:49
but he's there, he's taking服用 care關心 of the building建造.
244
574000
2000
不過他人在大樓裡 有在管事
09:51
But it's deteriorating惡化.
245
576000
2000
大樓慢慢老舊
09:53
And then suddenly突然, he learns獲悉 that there's going to be a hurricane颶風.
246
578000
3000
然後突然 管理員得知有颶風要來
09:56
So he doesn't actually其實 do anything himself他自己.
247
581000
2000
他自己實際上什麼都不做
09:58
He gets得到 on the telephone電話 --
248
583000
2000
而是拿起電話
10:00
just like FOXOFOXO gets得到 on the DNA脫氧核糖核酸 --
249
585000
2000
就像FOXO刺激DNA一樣
10:02
and he calls電話 up
250
587000
2000
然後打電話
10:04
the roofer蓋屋頂, the window窗口 person,
251
589000
2000
叫修屋頂 修窗戶的工人
10:06
the painter畫家, the floor地板 person.
252
591000
3000
油漆工 地板工
10:09
And they all come and they fortify強化 the house.
253
594000
2000
通通都過來 強化大樓
10:11
And then the hurricane颶風 comes through通過,
254
596000
2000
之後颶風過境
10:13
and the house is in much better condition條件 than it would normally一般 have been in.
255
598000
2000
不過大樓的狀況比平時改善許多
10:15
And not only that, it can also just last longer,
256
600000
3000
不只如此 它還可以維持更久
10:18
even if there isn't a hurricane颶風.
257
603000
2000
有沒有颶風都一樣
10:20
So that's the concept概念 here
258
605000
2000
我要說明的概念就是如此
10:22
for how we think this life extension延期 ability能力 exists存在.
259
607000
4000
所謂延長壽命的能力就是這樣
10:26
Now the really cool thing about FOXOFOXO
260
611000
2000
FOXO了不起的地方
10:28
is that there are different不同 forms形式 of it.
261
613000
2000
是它有各種不同的型態
10:30
We all have FOXOFOXO genes基因,
262
615000
3000
我們都有FOXO的基因
10:33
but we don't all have exactly究竟 the same相同 form形成 of the FOXOFOXO gene基因.
263
618000
3000
但是型態並不完全一樣
10:36
Just like we all have eyes眼睛,
264
621000
2000
就像我們都有眼睛
10:38
but some of us have blue藍色 eyes眼睛 and some of us have brown棕色 eyes眼睛.
265
623000
3000
但有些人的眼睛是藍色的 有些人的眼睛是棕色的
10:41
And there are certain某些 forms形式 of the FOXOFOXO gene基因
266
626000
3000
某些形態的FOXO基因
10:44
that have found發現 to be more frequently經常 present當下
267
629000
2000
我們發現 它們最常出現的地方
10:46
in people who live生活 to be 90 or 100.
268
631000
2000
是在90或100歲人瑞的體內
10:48
And that's the case案件 all over the world世界,
269
633000
2000
這種狀況 全世界都一樣
10:50
as you can see from these stars明星.
270
635000
2000
這張圖上的星星就足以說明
10:52
And each one of these stars明星 represents代表 a population人口
271
637000
2000
每一顆星代表一個人口族群
10:54
where scientists科學家們 have asked,
272
639000
2000
科學家在這些地方研究:
10:56
"Okay, are there differences分歧 in the type類型 of FOXOFOXO genes基因
273
641000
2000
「這裡的FOXO基因
10:58
among其中 people who live生活 a really long time?" and there are.
274
643000
3000
在長壽人口體內是否都不同?」的確如此
11:01
We don't know the details細節 of how this works作品,
275
646000
2000
我們不清楚這一切運作的細節
11:03
but we do know then
276
648000
2000
但我們知道
11:05
that FOXOFOXO genes基因 can impact碰撞
277
650000
2000
FOXO基因可以影響
11:07
the lifespan壽命 of people.
278
652000
2000
人類的壽命
11:09
And that means手段 that, maybe if we tweak it a little bit,
279
654000
3000
這就表示 如果我們善加利用這一點
11:12
we can increase增加 the health健康 and longevity長壽 of people.
280
657000
4000
就可以改善人類的健康 增加壽命
11:16
So this is really exciting扣人心弦 to me.
281
661000
2000
這一點讓我非常興奮
11:18
A FOXOFOXO is a protein蛋白 that we found發現 in these little, round回合 worms蠕蟲
282
663000
2000
FOXO這種蛋白質 在圓形小蟲子體內找到的
11:20
to affect影響 lifespan壽命,
283
665000
2000
會影響壽命
11:22
and here it affects影響 lifespan壽命 in people.
284
667000
2000
也可以影響人類的壽命
11:24
So we've我們已經 been trying in our lab實驗室 now
285
669000
2000
所以我們現在在實驗室
11:26
to develop發展 drugs毒品
286
671000
2000
試著研發藥物
11:28
that will activate啟用 this FOXOFOXO cell細胞
287
673000
2000
可以刺激FOXO
11:30
using運用 human人的 cells細胞 now
288
675000
2000
改用人類細胞
11:32
in order訂購 to try and come up with drugs毒品
289
677000
2000
才能進一步研發藥品
11:34
that will delay延遲 aging老化 and age-related年齡相關 diseases疾病.
290
679000
3000
延緩老化 和與年齡相關的疾病
11:37
And I'm really optimistic樂觀 that this is going to work.
291
682000
3000
我對於此事能否成功相當樂觀
11:40
There are lots of different不同 proteins蛋白質 that are known已知 to affect影響 aging老化.
292
685000
3000
現在已知有許多不同的蛋白質都會影響老化
11:43
And for at least最小 one of them, there is a drug藥物.
293
688000
3000
至少對其中一種 可以用藥物控制
11:46
There's one called TORTOR, which哪一個 is another另一個 nutrient養分 sensor傳感器,
294
691000
2000
這種蛋白質叫TOR 也是一種感應養分的蛋白質
11:48
like the insulin胰島素 pathway.
295
693000
2000
類似胰島素路徑
11:50
And mutations突變 that damage損傷 the TORTOR gene基因 --
296
695000
2000
如果TOR基因被突變破壞
11:52
just like the daf-daf-2 mutations突變 --
297
697000
2000
就會跟daf-2突變體一樣
11:54
extend延伸 lifespan壽命 in worms蠕蟲
298
699000
2000
可以延長蟲子的壽命
11:56
and flies蒼蠅 and mice老鼠.
299
701000
3000
對蒼蠅和老鼠也都有效
11:59
But in this case案件, there's already已經 a drug藥物 called rapamycin雷帕黴素
300
704000
2000
但是在這種情況 已經有一種叫rapamycin的免疫抑制劑
12:01
that binds結合 to the TORTOR protein蛋白
301
706000
2000
會附著在TOR蛋白質上
12:03
and inhibits抑制 its activity活動.
302
708000
2000
抑制它的活動
12:05
And you can take rapamycin雷帕黴素 and give it to a mouse老鼠 --
303
710000
3000
如果你讓老鼠服用這種免疫抑制劑
12:08
even when it's pretty漂亮 old, like age年齡 60 for a human人的,
304
713000
2000
即使老鼠已經很老 像個60歲的人
12:10
that old for a mouse老鼠 --
305
715000
2000
即使這種年齡的老鼠
12:12
if you give the mouse老鼠 rapamycin雷帕黴素,
306
717000
2000
如果服用免疫抑制劑
12:14
it will live生活 longer.
307
719000
2000
也會活更久
12:16
Now I don't want you all to go out taking服用 rapamycin雷帕黴素.
308
721000
2000
不過我並不是叫你們趕快去服用rapamycin
12:18
It is a drug藥物 for people,
309
723000
2000
它的確是人類使用的藥物
12:20
but the reason原因 is it suppresses禁止顯示 the immune免疫的 system系統.
310
725000
3000
但是它會抑制免疫系統
12:23
So people take it to prevent避免 organ器官 transplants移植 from being存在 rejected拒絕.
311
728000
4000
因此用來避免接受器官移植的病人產生排斥現象
12:27
So this may可能 not be the perfect完善 drug藥物
312
732000
2000
因此它不是靈丹妙藥
12:29
for staying young年輕 longer.
313
734000
2000
不是青春長駐的最佳選擇
12:31
But still, here in the year 2011,
314
736000
3000
但是 現在是2011年
12:34
there's a drug藥物 that you can give to mice老鼠 at a pretty漂亮 old age年齡
315
739000
2000
的確有一種藥 如果給年事已高的老鼠服用
12:36
that will extend延伸 their lifespan壽命,
316
741000
2000
可以延長牠們的壽命
12:38
which哪一個 comes out of this science科學
317
743000
2000
在研究中也證實
12:40
that's been doneDONE in all these different不同 animals動物.
318
745000
2000
對其他各種不同的動物也有效
12:42
So I'm really optimistic樂觀,
319
747000
2000
因此我相當樂觀
12:44
and I think it won't慣於 be too long, I hope希望,
320
749000
2000
也認為我們的夢想已經近在咫尺
12:46
before this age-old古老 dream夢想 begins開始 to come true真正.
321
751000
3000
長久以來青春長在的夢想即將成真
12:49
Thank you.
322
754000
2000
謝謝各位
12:51
(Applause掌聲)
323
756000
9000
(掌聲)
13:00
Matt馬特 Ridley雷德利: Thank you, Cynthia辛西婭.
324
765000
3000
麥特‧雷德利:謝謝妳 辛西亞
13:03
Let me get this straight直行.
325
768000
2000
讓我澄清一下情況
13:05
Although雖然 you're looking for a drug藥物
326
770000
2000
你在尋找的這種藥
13:07
that can solve解決 aging老化
327
772000
2000
可以解決老化的問題
13:09
in old men男人 like me,
328
774000
3000
對我種老頭子也有效
13:12
what you could do now pretty漂亮 well in the lab實驗室,
329
777000
3000
現在你在實驗室中已經可以做到
13:15
if you were allowed允許 ethically道德,
330
780000
2000
當然在不違背道德的前提下
13:17
is start開始 a human人的 life from scratch
331
782000
3000
無中生有創造一個人
13:20
with altered改變 genes基因 that would make it live生活 for a lot longer?
332
785000
3000
並擁有改變過的基因 讓它可以活更久嗎?
13:23
CKCK: Ah, so the kinds of drugs毒品 I was talking about
333
788000
3000
辛西亞:我剛剛說明的那種藥
13:26
would not change更改 the genes基因,
334
791000
2000
不會改變基因
13:28
they would just bind捆綁 to the protein蛋白 itself本身
335
793000
3000
只會附著在蛋白質上
13:31
and change更改 its activity活動.
336
796000
2000
改變其功能
13:33
So if you stop taking服用 the drug藥物, the protein蛋白 would go back to normal正常.
337
798000
3000
所以如果你停止服藥 蛋白質就會恢復成正常的狀態
13:36
You could change更改 the genes基因 in principle原理.
338
801000
3000
你也可以從基因上徹底改變
13:39
There isn't the technology技術 to do that.
339
804000
2000
不過現在還沒有這種科技
13:41
But I don't think that's a good idea理念.
340
806000
2000
但是我不覺得這是理想的做法
13:43
And the reason原因 is
341
808000
2000
因為
13:45
that these hormones激素,
342
810000
2000
這些荷爾蒙
13:47
like the insulin胰島素 and the IGFIGF hormones激素 and the TORTOR pathway,
343
812000
3000
像是胰島素 IGF 還有TOR路徑
13:50
they're essential必要.
344
815000
2000
是人體不可或缺的
13:52
If you knock them out completely全然, then you're very sick生病.
345
817000
3000
如果你徹底移除它們 會讓你生重病
13:55
So it might威力 be that you would just have to fine tune調 it very carefully小心
346
820000
3000
所以還是小心地做細微的調整
13:58
to get the benefits好處 without getting得到 any problems問題.
347
823000
3000
只取其益 免受其害
14:01
And I think that's much better,
348
826000
2000
我認為才是比較理想的做法
14:03
that kind of control控制 would be much better as a drug藥物.
349
828000
2000
這種控制才是理想的藥物
14:05
And also, there are other ways方法 of activating激活 FOXOFOXO
350
830000
3000
此外 還有其他方法可以刺激FOXO
14:08
that don't even involve涉及 insulin胰島素 or IGF-IGF-1
351
833000
2000
完全不涉及胰島素或IGF-1
14:10
that might威力 even be safer更安全.
352
835000
2000
是更安全的方法
14:12
MR先生: I wasn't suggesting提示 that I was going to go and do it, but ...
353
837000
3000
麥特:我沒有暗示說我想這麼做 不過...
14:15
(Laughter笑聲)
354
840000
2000
(笑聲)
14:19
There's a phenomenon現象 which哪一個 you have written書面 about and spoken about,
355
844000
4000
有一種現象 你有寫到也有提到
14:23
which哪一個 is a negligible微不足道 senescence衰老.
356
848000
3000
就是微不足道的老化
14:26
There are some creatures生物 on this planet行星 already已經
357
851000
2000
地球上有一些生物
14:28
that don't really do aging老化.
358
853000
3000
不太會變老
14:31
Just move移動 to one side for us, if you would.
359
856000
3000
麻煩靠過來一點 謝謝
14:34
CKCK: There are. There are some animals動物 that don't seem似乎 to age年齡.
360
859000
3000
辛西亞:的確 有些動物似乎不會變老
14:37
For example, there are some tortoises called Blanding's布蘭丁的 turtles海龜.
361
862000
4000
例如 有一種陸龜叫流星澤龜
14:41
And they grow增長 to be about this size尺寸.
362
866000
2000
可以長到這麼大
14:43
And they've他們已經 been tagged標記, and they've他們已經 been found發現 to be 70 years年份 old.
363
868000
3000
追蹤的結果 發現牠們可以活到70歲
14:46
And when you look at these 70 year-old turtles海龜,
364
871000
2000
當你看著這些70歲的烏龜
14:48
you can't tell the difference區別, just by looking,
365
873000
3000
如果只用看的 根本看不出差別
14:51
between之間 those turtles海龜 and 20 year-old turtles海龜.
366
876000
2000
牠們跟20歲的烏龜沒有兩樣
14:53
And the 70 year-old ones那些,
367
878000
2000
還有 70歲的烏龜
14:55
actually其實 they're better at scouting偵察 out the good nesting嵌套 places地方,
368
880000
3000
其實更善於找到良好的棲息地點
14:58
and they also have more progeny子孫 every一切 year.
369
883000
3000
每年也可以產下更多後代
15:01
And there are other examples例子 of these kinds of animals動物,
370
886000
3000
其他還有很多這類動物的例子
15:04
like turns, certain某些 kinds of birds鳥類 are like this.
371
889000
3000
像是燕鷗 或者其他鳥類就像這樣
15:07
And nobody沒有人 knows知道 if they really can live生活 forever永遠,
372
892000
2000
沒有人知道牠們是否可以長生不死
15:09
or what keeps保持 them from aging老化.
373
894000
2000
或為何牠們不會老化
15:11
It's not clear明確.
374
896000
2000
現在還不清楚
15:13
If you look at birds鳥類, which哪一個 live生活 a long time,
375
898000
3000
如果你觀察鳥類 長壽的鳥類
15:16
cells細胞 from the birds鳥類 tend趨向 to be more resistant
376
901000
3000
牠們的細胞通常較具抵抗力
15:19
to a lot of different不同 environmental環境的 stresses應力
377
904000
2000
可以應對許多環境壓力
15:21
like high temperature溫度
378
906000
2000
例如高溫
15:23
or hydrogen peroxide過氧化物, things like that.
379
908000
2000
或過氧化氫這類的東西
15:25
And our long-lived長壽命 mutants突變體 are too.
380
910000
2000
長壽的突變種生物也是這樣
15:27
They're more resistant to these kinds of stresses應力.
381
912000
2000
牠們比較能抵抗這些壓力
15:29
So it could be that the pathways途徑 that I've been talking about,
382
914000
3000
所以有可能是我剛剛說明的那些路徑
15:32
which哪一個 are set to run really quickly很快 in the worm,
383
917000
3000
在蟲子體內運轉得非常快
15:35
have a different不同 normal正常 set point
384
920000
3000
但在不同生物體內速度會不同
15:38
in something like a bird, so that a bird can live生活 a lot longer.
385
923000
3000
例如鳥類 因此某隻鳥可以活較久
15:41
And maybe they're even set really differently不同
386
926000
2000
甚至可能這些路徑運轉的速度
15:43
in animals動物 with no senescence衰老 at all -- but we don't know.
387
928000
3000
在不會老化的動物體內是完全不同的 這一點尚待確認
15:46
MR先生: But what you're talking about here
388
931000
2000
麥特:但是你剛剛說的
15:48
is not extending擴展 human人的 lifespan壽命
389
933000
3000
不是延長人類的壽命
15:51
by preventing防止 death死亡,
390
936000
2000
預防死亡
15:53
so much as extending擴展 human人的 youthspanyouthspan.
391
938000
2000
而是延長青春歲月
15:55
CKCK: Yes, that's right.
392
940000
2000
辛西亞:對 就是這樣
15:57
It's more like, say, if you were a dog.
393
942000
2000
比較像是 假設你是一隻狗
15:59
You notice注意 that you're getting得到 old, and you look at your human人的
394
944000
2000
注意到自己開始變老了 不過你看看你的主人
16:01
and you think, "Why isn't this human人的 getting得到 old?"
395
946000
2000
心裡想:為什麼這個人類不會變老?
16:03
They're not getting得到 old in the dog's小狗 lifespan壽命.
396
948000
2000
人類不會在狗的有生之年變老
16:05
It's more like that.
397
950000
2000
我說的比較像是這種情況
16:07
But now we're the human人的 looking out and imagining想像 a different不同 human人的.
398
952000
4000
但現在我們是以人類的角度 去想像另一種人類
16:11
MR先生: Thank you very much indeed確實, Cynthia辛西婭 Kenyon肯揚.
399
956000
3000
麥特:非常感謝辛西亞‧凱尼恩
16:14
(Applause掌聲)
400
959000
3000
(掌聲)
Translated by Michelle Fan
Reviewed by Shelley Krishna R. TSANG

▲Back to top

ABOUT THE SPEAKER
Cynthia Kenyon - Biochemist, geneticist
When it comes to aging well, having “good genes” (or rather, mutant ones) is key, says Cynthia Kenyon. She unlocked the genetic secret of longevity in roundworms — and now she’s working to do the same for humans.

Why you should listen

Cynthia Kenyon is revolutionizing our understanding of aging. As an expert in biochemistry and biophysics at the University of California at San Francisco, she is particularly interested in the influence that genetics have on age-related diseases (from cancer to heart failure) in living things.

Her biggest breakthrough was figuring out that there’s a “universal hormonal control for aging”: carbohydrate intake, which can have a dramatic effect on how two critical genes behave, reducing insulin production and boosting repair and renovation activities. So far, her theory has proved true for worms, mice, rats, and monkeys — and she suspects it applies to humans, too.

By studying aging, Kenyon believes that she and other scientists (many of whom have successfully duplicated her experiments) will be able to pinpoint the molecules responsible for the onset of age-related diseases in people and prevent them. She’s co-founded a drug-development company called Elixir Pharmaceuticals to do just that.

She says: "The link between aging and age-related disease suggests an entirely new way to combat many diseases all at once; namely, by going after their greatest risk factor: aging itself."

More profile about the speaker
Cynthia Kenyon | Speaker | TED.com