Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Philos Trans R Soc Lond B Biol Sci. 2011 Jan 12;366(1561):17-27. doi: 10.1098/rstb.2010.0198.
Studies in invertebrate model organisms have led to a wealth of knowledge concerning the ageing process. But which of these discoveries will apply to ageing in humans? Recently, an assessment of the degree of conservation of ageing pathways between two of the leading invertebrate model organisms, Saccharomyces cerevisiae and Caenorhabditis elegans, was completed. The results (i) quantitatively indicated that pathways were conserved between evolutionarily disparate invertebrate species and (ii) emphasized the importance of the TOR kinase pathway in ageing. With recent findings that deletion of the mTOR substrate S6K1 or exposure of mice to the mTOR inhibitor rapamycin result in lifespan extension, mTOR signalling has become a major focus of ageing research. Here, we address downstream targets of mTOR signalling and their possible links to ageing. We also briefly cover other ageing genes identified by comparing worms and yeast, addressing the likelihood that their mammalian counterparts will affect longevity.
在无脊椎动物模式生物中的研究已经积累了大量有关衰老过程的知识。但是,这些发现中有哪些可以应用于人类的衰老呢?最近,对两种领先的无脊椎动物模式生物——酿酒酵母和秀丽隐杆线虫之间衰老途径的保守程度进行了评估。结果(i)定量表明,进化上不同的无脊椎物种之间存在途径保守性,(ii)强调了 TOR 激酶途径在衰老中的重要性。最近的研究发现,删除 mTOR 底物 S6K1 或使小鼠暴露于 mTOR 抑制剂雷帕霉素中会导致寿命延长,因此 mTOR 信号转导已成为衰老研究的主要焦点。在这里,我们研究了 mTOR 信号转导的下游靶标及其与衰老的可能联系。我们还简要介绍了通过比较蠕虫和酵母鉴定的其他衰老基因,探讨了它们的哺乳动物对应物是否会影响寿命的可能性。