African killifish may hold key to stopping ageing in
humans
Nicola Davis,The Guardian Fri, Feb 21 3:00 AM GMT+8
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African killifish may hold key to stopping ageing in humans.
Turquoise killifish is able to suspend its development for longer than its
average lifespan
The curious ability of the African turquoise killifish to
press pause on its development could have intriguing implications for human ageing,
say researchers.
Certain creatures, including the killifish, can put
themselves into suspended animation as an embryo – a trait known as diapause.
The phenomenon is thought to have evolved in response to pressures such as
seasonal changes in the environment – for example ponds drying up – or sudden
challenges that pose a risk to the creatures. In other words, diapause allows
the animal to put its development or birth on ice until conditions improve.
In the case of the African turquoise killifish, this means
that embryos can pause their development for months or even years – longer than
their adult lifetime of about four to six months. Scientists say the trait is
likely to be linked to annual droughts.
“We
actually don’t think the mechanism of diapause is directly caused by drought,”
said Prof Anne Brunet, co-author of the research from Stanford University. “But
the mechanism is indirectly linked to drought in the sense that drought
provided a selective pressure for this African turquoise killifish species:
over millions of years of evolution, the African killifish evolved to survive
drought by having its embryos enter a state of diapause.”
While the process is thought to be genetically programmed,
quite how it works has been something of a puzzle.
Now scientists say they have unpicked
the mechanism behind the phenomenon, and have revealed that pausing development
as an embryo has no impact on the fish’s future lifespan, fertility or how
large they grow as an adult – suggesting the impact of time on cells and
tissues themselves was suspended.
“Diapause
is a fascinating state of ‘suspended life’ that can preserve a complex organism
long-term, with no apparent tradeoff for subsequent life,” said Brunet.
Writing in the journal Science, Brunet and colleagues report
how they probed the processes involved in diapause in killifish embryos,
revealing the phenomenon involves genes involved in cell proliferation and
organ development being dialled down, while the activity of genes linked to
muscle maintenance and metabolism is also affected.
Part of this seems to be down to increase in the production
of a protein called CBX7. In the nucleus, DNA is packaged up by being wrapped
around proteins called histones – CBX7 binds to particular histones. The team
say this binding appears to influence the activity of a number of genes,
including some involved in muscle function and metabolism, resulting in muscle
being maintained throughout diapause.
The team say it may be possible to apply these mechanisms to
adults. As an accompanying editorial notes, this has previously been tried in a
simpler organism – the roundworm C elegans, whose larvae can undergo diapause –
and been found to extend longevity.
“One can
hypothesise that turning on a “diapause-like” state – or tapping into the
molecular machinery of diapause – in some adult tissues or cells could help
preserve them long-term,” said Brunet.
Could this lead to a way to stop ageing in humans? “We think
it’s interesting from a fundamental point of view to understand how the
accumulation of the damage due to the passage of time can be stopped or
suspended. Diapause offers us a way to understand this,” said Brunet. Such an
understanding may provide clues as to how to slow the “ageing clock”, she said,
but added that at present it is still speculative.
Prof Paul Shiels, an expert in
biological ageing from the University of Glasgow, said that while the authors
point to similarities between diapause and other types of suspended animation,
such as hibernation, they probably involve at least some different processes –
not least since hibernation involves the preservation of organs in their adult
form, rather than arresting their development.
Shiels said it was not clear how the new study could offer
ways to slow or prevent human ageing, since this would involve keeping adult
tissues in a suspended state. “[The study] has implications for organ regeneration,”
he said. “Whereas organ preservation, you’d [learn] more from hibernating
mammals.”
Translation
非洲小河魚可能是阻止人類衰老的關鍵。綠松石小河魚能暫停其發育的時間是可以超過其平均壽命
研究人員說，非洲的綠松石小河魚會暫停其發展的奇特能力，這可能會對人類的衰老產生深遠的影響。
某些生物，包括小河魚，可以使自己像胚胎一樣處於懸浮狀態，這就是滯育。人們認為，這種現像是隨著環境壓力的季節性變化（例如池塘幹乾涸）或突然對生物造成危險的挑戰而演變而來的。換句話說，滯育使動物能夠將其發育或出生停頓，直到狀況改善為止。
以非洲非洲的綠松石小河魚為例，這意味著胚胎可以暫停其發育長達數月甚至數年，這比其成年壽命約四到六個月更長。科學家說，這種特性很可能與每年的干旱有關。
斯坦福大學研究報告的合著者安妮·布魯內特教授說：“實際上，滯育的機制並不是乾旱造成的。”
“但是從某種意義上說，這種機制與乾旱間接相關，因為乾旱為非洲綠松石小河魚提供了選擇性壓力：經過數百萬年的進化，非洲小河魚通過使其胚胎進入滯育狀態而在乾旱中生存。”
雖然這個過程被認為是基因程式設計的，但其運作方式還是個謎。
現在，科學家表示，他們已經拆解這種現象背後的機制，並揭示了暫停發育為胚胎不會影響魚的未來壽命，繁殖力或成年後的成年量，這表明暫停了時間對細胞和組織本身的影響。
布魯內特說：“滯育是'暫停生命'的一種令人著迷的狀態，它可以長期保存複雜的有機體，而在隨後的生命中沒有明顯的代價。”
Brunet及其同事在《科學》雜誌上發表文章，報導了他們如何探測小河魚胚胎滯育的過程，揭示了涉及與細胞增殖的基因的有關現象,
和器官發育縮小，而與肌肉維持和代謝有關的基因的活動也受到影響。
這種現象的一部分似乎是由於一種叫做CBX7的蛋白質的產量增加所致。在細胞核中，DNA被包裹在稱為組蛋白的蛋白質周圍 —— CBX7 與特定的組蛋白結合。研究小組說這種結合似乎會影響許多基因的活動，包括一些參與肌肉功能和新陳代謝的基因，導致肌肉在整個滯育過程中得以養護。
研究小組表示，有可能將這些機制應用於成年人。作為附帶的编者注釋: 以前已在較簡單的有機體 - 線蟲C
elegans中進行了嘗試，該蟲的幼蟲可能會滯育-並可以延長其壽命。
布魯內特說：“有人可以假設，利用啟動進入“類似滯性”的狀態，或利用滯育的分子機制，在將有助於某些成年組織或細胞能够長期保存。
這會導致一種阻止人類衰老的方法嗎？ 布魯內特說, “從根本的角度來看是很有趣的，我們理解如何隨著時間的流逝而造成的累積損害可以被制止或暫停。滯育為我們提供了一種了解這一點的方式。”她說，這種理解可能為如何減緩“老齡化時鐘”提供線索，但補充說，目前它仍是推測性的。
格拉斯哥大學的生物衰老專家Paul
Shiels教授說，儘管作者指出了滯育與其他類型的暫停活力例如休眠之間的相似之處，但它們可能至少涉及一些不同的過程
-尤其是因為休眠涉及保存成年器官，而不是阻止其發育。
Shiels表示，目前尚不清楚新的研究如何提供減緩或防止人類衰老的方法，因為這將使成人組織保持暫停狀態。他說： “[這項研究]對器官再生有影響”;
“對於器官保存，您從冬眠的哺乳動物中[學到]更多。”
So, this is
another attempt of the scientists to find a way to extend longevity of living
things, including human.
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