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果蝇衰老的分子遗传学:这是开始的结束吗?

Molecular genetics of aging in the fly: is this the end of the beginning?

作者信息

Helfand Stephen L, Rogina Blanka

机构信息

Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030-3301, USA.

出版信息

Bioessays. 2003 Feb;25(2):134-41. doi: 10.1002/bies.10225.

Abstract

How we age and what we can do about it have been uppermost in human thought since antiquity. The many false starts have frustrated experimentalists and theoretical arguments pronouncing the inevitability of the process have created a nihilistic climate among scientists and the public. The identification of single gene alterations that substantially extend life span in nematodes and flies however, have begun to reinvigorate the field. Drosophila's long history of contributions to aging research, rich storehouse of genetic information, and powerful molecular techniques make it an excellent system for studying the molecular mechanisms underlying the process of aging. In recent years, Drosophila has been used to test current theories on aging and explore new directions of potential importance to the biology of aging. One such example is the surprising finding that, as opposed to the commonly held assumption that adult life is a period of random passive decline in which all things are thought to fall apart, the molecular life of the adult fly appears to be a state of dynamic well-regulated change. In the fly, the level of expression of many different genes changes in an invariant, often age-dependent, manner. These as well as other molecular genetic studies and demographic analyses using the fly have begun to challenge widely held ideas about aging providing evidence that aging may be a much more dynamic and malleable process than anticipated. With the enormous success that Drosophila molecular genetics has demonstrated in helping understand complex biological phenomena such as development there is much optimism that similar approaches can be adapted to assist in understanding the process of aging.

摘要

自古以来,人类如何衰老以及我们对此能做些什么一直是人们思考的首要问题。许多无果而终的尝试让实验者感到沮丧,而宣称衰老过程不可避免的理论观点在科学家和公众中营造了一种虚无主义的氛围。然而,对线虫和果蝇中能显著延长寿命的单基因改变的识别,已开始为该领域注入新的活力。果蝇在衰老研究方面有着悠久的贡献历史、丰富的遗传信息库以及强大的分子技术,使其成为研究衰老过程潜在分子机制的理想系统。近年来,果蝇已被用于检验当前的衰老理论,并探索对衰老生物学具有潜在重要性的新方向。一个这样的例子是一个惊人的发现,与普遍认为成年期是一个随机被动衰退的时期,在此期间所有事物都会逐渐瓦解的假设相反,成年果蝇的分子生命似乎是一种动态且调控良好的变化状态。在果蝇中,许多不同基因的表达水平会以一种不变的、通常与年龄相关的方式发生变化。这些以及其他使用果蝇进行的分子遗传学研究和人口统计学分析,已开始挑战关于衰老的广泛观点,提供了证据表明衰老可能是一个比预期更具动态性和可塑性的过程。鉴于果蝇分子遗传学在帮助理解诸如发育等复杂生物学现象方面所取得的巨大成功,人们非常乐观地认为类似的方法可被用于协助理解衰老过程。

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