?威斯康辛大学William Engels博士日前揭示,老龄化进程与细胞代谢和环境因素所造成的DNA损伤有关,而研究发现果蝇幼体会充分利用各种DNA的分子修复机制。该结果将刊登于24日出版的《当今生物学》杂志上。
??DNA修复对于基因信息的精确保存及细胞基本功能的正常发挥都至关重要,长期以来科学家们就怀疑老龄化与DNA的损伤有关。证据之一便是人类和其他哺乳动物体内某些基因的损伤修复过程会诱发加速老龄化进程的疾病,如恶性肿瘤, 骨质疏松,失聪,脱发等。并且DNA损伤也会加速各组织器官细胞的衰老。
??DNA链的损伤有很多原因,往往发生于自然的细胞生长过程中。修复这样的损伤是必要的,然而也是非常危险的,经常会丢失或增加一些碱基对。细胞也有很多修复受损DNA的方法,而选择哪一种则显得非常重要。有些修复手段简单但错误率高,而更精确的方法则需要精细的分子元件,并且很耗时。
??该最新结果表明果蝇幼体细胞往往采取粗犷的修复方式,因此并不需要复杂的DNA合成过程,也不需要配对的DNA模板。而当器官老化后,同一损伤的修复会采取耗时但更精确的方法,会充分利用配对的模板。这些结果即形成一个疑问:幼体这些迅速而错误率高的DNA修复方式是否会直接导致基因损伤的积累从而加速老龄化进程。而成体细胞或许会选择更安全的修复方式,但它们仍然携带幼体时保留下的损伤基因。
美国威斯康星州立大学的研究者，在前天发表于Current Biology期刊中的研究指出，年轻果蝇的细胞会利用一种与年纪较大果蝇细胞不同的DNA修补机制，但可能是造成老化的原因。
DNA修补是维持精准正确的遗传密码与细胞生理代谢正常的必要机制，也被认为可能与老化和DNA损伤有关。研究者发现，由于DNA 修补机制中所需的蛋白基因遗失了，以人类或哺乳类动物为例，恶性肿瘤、骨质疏松、失聪、头发渐白与掉发都是因为相关基因因为失效而无法执行正常的功能所造成。
在自然的生理代谢中，DNA断裂是常见的；需要适当的修补机制来挽救。有些修补机制简单但易出错，有些则复杂且缓慢但精准性高。正确的选择出适当的修补机制是保持DNA正确的关键。
研究者发现，年轻的果蝇细胞会执行一种不必与DNA配对的简单修补机制，但年老的细胞却谨慎且缓慢的完整修补。这似乎说明，年轻时候快速的修补可能累积各种导致老化的损伤与错误。虽然尚未有明确而清晰的机制发现，但这项研究无疑的给想要了解老化秘密的学者提出一个重要的问题。
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.
