?威斯康辛大學William Engels博士日前揭示,老齡化進程與細胞代謝和環(huán)境因素所造成的DNA損傷有關(guān),而研究發(fā)現(xiàn)果蠅幼體會充分利用各種DNA的分子修復機制。該結(jié)果將刊登于24日出版的《當今生物學》雜志上。
??DNA修復對于基因信息的精確保存及細胞基本功能的正常發(fā)揮都至關(guān)重要,長期以來科學家們就懷疑老齡化與DNA的損傷有關(guān),。證據(jù)之一便是人類和其他哺乳動物體內(nèi)某些基因的損傷修復過程會誘發(fā)加速老齡化進程的疾病,如惡性腫瘤, 骨質(zhì)疏松,失聰,脫發(fā)等。并且DNA損傷也會加速各組織器官細胞的衰老,。
??DNA鏈的損傷有很多原因,往往發(fā)生于自然的細胞生長過程中。修復這樣的損傷是必要的,然而也是非常危險的,經(jīng)常會丟失或增加一些堿基對,。細胞也有很多修復受損DNA的方法,而選擇哪一種則顯得非常重要,。有些修復手段簡單但錯誤率高,而更精確的方法則需要精細的分子元件,并且很耗時。
??該最新結(jié)果表明果蠅幼體細胞往往采取粗獷的修復方式,因此并不需要復雜的DNA合成過程,也不需要配對的DNA模板,。而當器官老化后,同一損傷的修復會采取耗時但更精確的方法,會充分利用配對的模板,。這些結(jié)果即形成一個疑問:幼體這些迅速而錯誤率高的DNA修復方式是否會直接導致基因損傷的積累從而加速老齡化進程。而成體細胞或許會選擇更安全的修復方式,但它們?nèi)匀粩y帶幼體時保留下的損傷基因,。
美國威斯康星州立大學的研究者,，在前天發(fā)表于Current Biology期刊中的研究指出,，年輕果蠅的細胞會利用一種與年紀較大果蠅細胞不同的DNA修補機制，但可能是造成老化的原因,。
DNA修補是維持精準正確的遺傳密碼與細胞生理代謝正常的必要機制,，也被認為可能與老化和DNA損傷有關(guān)。研究者發(fā)現(xiàn),，由于DNA 修補機制中所需的蛋白基因遺失了，以人類或哺乳類動物為例,，惡性腫瘤,、骨質(zhì)疏松、失聰,、頭發(fā)漸白與掉發(fā)都是因為相關(guān)基因因為失效而無法執(zhí)行正常的功能所造成,。
在自然的生理代謝中，DNA斷裂是常見的,；需要適當?shù)男扪a機制來挽救,。有些修補機制簡單但易出錯，有些則復雜且緩慢但精準性高,。正確的選擇出適當?shù)男扪a機制是保持DNA正確的關(guān)鍵,。
研究者發(fā)現(xiàn)，年輕的果蠅細胞會執(zhí)行一種不必與DNA配對的簡單修補機制,，但年老的細胞卻謹慎且緩慢的完整修補,。這似乎說明，年輕時候快速的修補可能累積各種導致老化的損傷與錯誤,。雖然尚未有明確而清晰的機制發(fā)現(xiàn),，但這項研究無疑的給想要了解老化秘密的學者提出一個重要的問題。
英文原文：
Age-related Changes In DNA Repair Illuminate The Connection Between Age And Genetic Damage
Researchers have uncovered a new way in which the aging process is linked to DNA damage--which occurs normally as a result of cell metabolism and environmental influences--and the various ways in which cells repair that damage. In the new work, researchers found that cells in young fruit flies make use of a different mix of molecular DNA-repair mechanisms compared to cells in older flies. The findings are reported by William Engels and colleagues at the University of Wisconsin and appear in the October 24th issue of the journal Current Biology, published by Cell Press.
DNA repair is essential for the accurate preservation of genetic information and to ensure the healthy functioning of cells, and a connection between aging and DNA damage has long been suspected. One line of evidence supporting the connection is that defects in certain genes needed for DNA repair produce maladies that mimic those of accelerated aging. In humans and other mammals, these effects include elevated occurrence of malignancies, osteoporosis, hearing loss, graying of hair, and hair loss. It is also known that DNA damage accumulates with age in cells of a variety of tissue types.
Breaks in the DNA chain have a variety of causes and occur frequently in the course of natural cellular processes. Repairing such breaks is an essential but hazardous process, often leaving missing or added bases at the point of repair. Cells possess a variety of methods for repairing broken DNA, and the cell's "choice" of how to repair a particular break can be critical. Some repair methods are simple but error prone, whereas the more accurate methods have elaborate molecular requirements and are probably much slower.
The new results show that the reproductive cells of young flies tend to use the rough-and-ready repair processes that do not involve extensive DNA synthesis and do not require a matching DNA template for the repair. As the organisms age, however, the same kind of DNA breaks are repaired primarily by the slower but much more accurate methods that make use of a matching template. These findings raise the question of whether the rapid but risky methods of DNA repair used by cells of young individuals contribute to the accumulation of genetic damage, and perhaps to the aging process itself. Older cells may use the safer repair methods, but they still carry the genetic damage incurred during DNA repair in the fly's "reckless" youth.
