Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
J Biochem. 2011 Apr;149(4):381-8. doi: 10.1093/jb/mvr026. Epub 2011 Mar 3.
Traditionally, ageing has been considered a passive and entropic process, in which damages accumulate on biological macromolecules over time and the accumulated damages lead to a decline in overall physiological functions. However, the discovery of a longevity mutant in the nematode Caenorhabditis elegans has challenged this view. A longevity mutant is a mutant organism, in which a reduction-of-function of a certain gene prolongs the lifespan. Thus, the discovery of longevity mutants has shown the existence of genes, which function to shorten lifespan in wild-type organisms, promoting extensive hunting for longevity-regulating genes in short-lived model organisms, such as yeast, worms and flies. These studies have revealed remarkable conservation of longevity-regulating genes and their networks among species. Decreased insulin/IGF-like signalling and decreased target of rapamycin (TOR) signalling are both shown to extend lifespan in evolutionarily divergent species, from unicellular organisms to mammals. Intriguingly, most of these longevity-regulating pathways reveal pro-longevity and anti-longevity effects on lifespan, depending on biological and environmental contexts. This review summarizes pleiotropic functions of the conserved longevity-regulating genes or pathways, focusing on studies in C. elegans.
传统上，衰老被认为是一个被动和熵增的过程，随着时间的推移，生物大分子上的损伤不断积累，而累积的损伤导致整体生理功能下降。然而，秀丽隐杆线虫（Caenorhabditis elegans）长寿突变体的发现挑战了这一观点。长寿突变体是指一种功能丧失型突变体，其特定基因的功能丧失会延长寿命。因此，长寿突变体的发现表明存在某些基因，这些基因在野生型生物中起缩短寿命的作用，这促使人们在酵母、线虫和果蝇等寿命较短的模式生物中广泛寻找长寿调控基因。这些研究揭示了长寿调控基因及其网络在物种间的显著保守性。减少胰岛素/IGF 样信号和雷帕霉素靶蛋白（TOR）信号都被证明能延长进化上不同的物种的寿命，从单细胞生物到哺乳动物。有趣的是，这些长寿调控途径中的大多数在依赖于生物和环境的情况下，对寿命表现出延长寿命和缩短寿命的双重作用。本文综述了保守的长寿调控基因或途径的多功能性，重点介绍了秀丽隐杆线虫的研究。
