A cure for ageing? Scientists discover breakthrough procedure to replace specific parts of ageing cells

 

長生不老藥成真?科學家發現能修復老化細胞的突破性

程序

 

  •     As we age, our mitochondrial DNA mutates, eventually killing off cells

 

          當我們老化,我們細胞中的粒線體基因突變,最終扼殺細胞。

 

 

   •     Mitochondria are not good at naturally repairing mutations

 

          粒線體不擅長自然地恢復突變。

          

   •     Scientists at Caltech and UCLA have developed a way to over-express certain genes, triggering mitochondria to clear out mutated genes

 

          加州理工學院California Institute of Technology,縮寫Caltech )以及加州大學洛杉磯分校(University of California, Los Angeles,縮寫UCLA )的科學家們發展出一個使某些特定基因過度表現(over-express)的方法,使產生突變的粒線體清除突變的基因。

 

   •     It’s a slight twist on the method that won 2016’s Nobel Prize for Science

         (這裡怪怪的,諾貝爾獎有物理獎(Physics Prize)、化學獎(Chemistry Prize)、生裡學或醫學獎(Physiology or Medicine Prize)、文學獎(Literature Prize)、和平獎(Peace Prize)、經濟學獎(Swedish National Bank’s Prize in Economic Sciences in Memory of Alfred Nobel),並沒有Nobel Prize for Science ,考慮2016 化學獎的內容較符合,翻為諾貝爾化學獎)

 

           這個方法是以2016 年的諾貝爾化學獎得主的研究成果為基礎,加入些微改變後得出。  

 

   •     The op, tested on flies, could pave the way for age-halting ops on humans

 

          這個在蒼蠅上實施的手術,可以為人類的凍齡手術鋪路。

 

A landmark study has identified a new way to replace ageing cells in our body.

The research by scientists at Caltech and UCLA could pave the way to developing nip-n-tuck style procedures that reverse and slow the ageing process.  

The experiment targeted mutated DNA inside our mitochondria – the ‘battery’ of our cells.

As we age, our DNA breaks down and mutates. But unlike other parts of the body, the mitochondria are not very good at repairing DNA.

But now, in a groundbreaking procedure, the Caltech-UCLA team has found a way to manipulate genes so that they break down and remove mutated DNA, regenerating the cells. 

 

一個里程碑般的研究找出一個可以復原我們體內老化細胞的新方法。這個由加州理工學院以及加州大學洛杉磯分校的科學家進行的研究,可為逆轉老化、延緩老化過程的程序們的發展鋪路。這個實驗針對我們體內的粒線體,也就是我們細胞的「電池」的突變基因。當我們變老,我們的基因分解並且突變。但,不像身體的其他部分,粒線體並不是很擅長修復基因。但是現在,在一個開創性的程序中,加州理工學院以及加州大學洛杉磯分校團隊(Caltech-UCLATeam )找到一個可以操縱基因,使基因分解並消除突變基因,使細胞再生的方法。

 

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The Caltech-UCLA team has found a way to manipulate genes so that they break down and remove mutated DNA, regenerating the cells

 

加州理工學院以及加州大學洛杉磯分校團隊(Caltech-UCLATeam )找到一個可以操縱基因,使基因分解並消除突變基因,使細胞再生的方法。

 

The operation is a twist on an already-documented natural procedure called autophagy (‘self-eating’).

Via autophagy, cells can digest dysfunctional mitochondria, clearing the way for healthy replacements.

It is a hot topic at the moment – in fact, it was research into autophagy that earned a Nobel Prize this year. 

But prior to the Caltech-UCLA study released on Monday, it was unclear whether this process could also promote the selective elimination of mutant or ageing DNA. 

 

這個手術改造自一個已經被詳細記錄過的自然程序,自噬作用(autophagy),「自我吞食」。透過自噬作用,細胞可以清除機能失常的粒線體,為健康的替補清出空間。這是一個很火熱的題目,事實上,今年的諾貝爾獎得主就是研究自噬作用。但優先於這份報告(加州理工學院以及加州大學洛杉磯分校團隊在星期一發布的研究報告)的是,我們依然不清楚,這個程序是否同時能促進消除被挑選的突變或老化基因。


The accumulation of mutant mtDNA over a lifetime is thought to contribute to aging and degenerative diseases of aging such as Alzheimer’s, Parkinson’s, and sarcopenia— age-related muscle loss and frailty. 

 

一生中所累積的突變粒線體基因(mtDNA)被認為是老化以及退化性疾病(degenerative diseases)的推進成因。例如:阿茲海默症(Alzheimers)、帕金森氏症(Parkinsons),以及肌少症(sarcopenia),一種老年性(age-related)的、失去肌肉與肌肉弱化的病症。

 

 

Inherited defects in mtDNA are also linked to a number of conditions found in children, including autism. 

‘We know that increased rates of mtDNA mutation cause premature aging,’ says Bruce Hay, Caltech professor of biology and biological engineering.

‘This, coupled with the fact that mutant mtDNA accumulates in key tissues such as neurons and muscle that lose function as we age, suggests that if we could reduce the amount of mutant mtDNA, we could slow or reverse important aspects of aging.’

To test their method, the team used a common fruit fly. 

 

粒線體基因的遺傳性缺陷同時與許多孩童的情形相關,例如自閉症。

 

來自加州理工學院,生物學以及生物工程學教授Bruce Hay表示:「我們知道突變粒線體基因的生成速率增加導致提早老化。同時,突變粒線體基因在重點組織,例如神經元以及肌肉的累積,會導致機能隨老化衰敗,從這些我們可以得出,如果我們能減少突變粒線體基因的數量,我們就能減緩或逆轉一些重大的老化現象。」

 

為了測試他們的理論,加州理工學院以及加州大學洛杉磯分校團隊(Caltech-UCLATeam )使用果蠅來作為實驗對象。

 

They focused on mitochondrial DNA in the muscles it uses to fly, since this is one of the most energy-draining tissues in the animal kingdom.

Like in humans, fruit flies’ muscles show some of the clearest signs of ageing. 

Fruit flies and humans are share many disease genes.

In the experiment, the fruit fly was genetically engineered so that 75 percent of its mtDNA was mutated early on.

They then artificially increased the activity of genes that promote mitophagy.

In doing so, the fraction of mutated mtDNA in the fly muscle cells was dramatically reduced. 

One gene in particular – called ‘parkin’ – reduced the fraction of mutant mtDNA from 76 percent to 5 percent when it was overexpressed.

 

他們聚焦在果蠅肌肉中的粒線體基因,因為這是動物王國中最耗能的組織。如同人類,果蠅的肌肉顯現了一些最清楚的老化徵兆。果蠅和人類有蠻多相同的疾病基因,在實驗中,果蠅的基因被操縱,所以果蠅百分之七十五的粒線體基因被突變。接著,實驗小組人為增加可促進粒線體自噬(mitophagy,粒線體經由自噬作用而降解的機制)的基因的活動。在實驗過程中,果蠅肌肉中的變異粒線體基因的百分比戲劇性地減少。舉例一種叫「parkin 」的基因,當它被刻意「過度表現」時,突變粒線體基因的百分比從百分之七十六減少到百分之五。

 

 

Our goal is to create a future in which we can periodically undergo a cellular housecleaning to remove damaged mtDNA from the brain, muscle, and other tissues

 

Bruce Hay, Caltech professor of biology and biological engineering

 

來自加州理工學院,生物學以及生物工程學教授Bruce Hay表示:「我們的目標是創造一個未來,一個能定期大掃除,將損壞的粒線體基因從腦部、肌肉以及其他組織消除的未來。」

 

Another gene – called ‘Atg1’ – reduced the fraction to 4 percent.

 

These are both genes which seem to be underactive in elderly people and people with degenerative diseases like Parkinson’s.  

 

另一個叫「Atg1」的基因,可以將突變粒線體基因的百分比降到百分之四。

 

這兩個基因似乎都能減少老化的人以及得到退化性疾病的人,例如帕金森氏症的患者。

 

 

‘Such a decrease would completely eliminate any metabolic defects in these cells, essentially restoring them to a more youthful, energy-producing state,’ Professor Hay said. 

‘The experiments serve as a clear demonstration that the level of mutant mtDNA can be reduced in cells by gently tweaking normal cellular processes.’ 

He added: ‘Our goal is to create a future in which we can periodically undergo a cellular housecleaning to remove damaged mtDNA from the brain, muscle, and other tissues. 

‘This will help us maintain our intellectual abilities, mobility, and support healthy aging more generally.’

 

Bruce Hay表示:「這樣的消除可完全除去任何細胞內突變性的缺陷,實質上將細胞恢復為更年輕、更有產能的狀態。這個實驗清楚地示範,輕輕地改變一點細胞的生化過程,就可以消除變異粒線體基因。我們的目標是創造一個未來,一個能定期大掃除,將損壞的粒線體基因從腦部、肌肉以及其他組織消除的未來。這將幫助我們維持我們的智能、活動能力,並更普遍地支持健康耆年(healthy aging)。」

 

 

來源:   dailymail