Lifespan extension in C-elegans by a molecular chaperone dependent upon insulin-like signals
Lifespan extension in C-elegans by a molecular chaperone dependent upon insulin-like signals
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DOI：
10.1046/j.1474-9728.2003.00045.x
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发表时间：
2003-04-01
期刊：
影响因子：
7.8
通讯作者：
Lithgow, GJ
中科院分区：
文献类型：
--
作者：
Walker, GA;Lithgow, GJ
胰岛素样信号是包括哺乳动物在内的不同物种寿命的关键决定因素，但这种途径影响衰老速度的机制尚不清楚。在线虫秀丽隐杆线虫中，胰岛素样信号通路的突变延长了成虫寿命，并与包括热休克蛋白（HSP）在内的应激反应基因的上调有关。我们检验了C. elegans胰岛素样信号通路通过调节HSP水平决定寿命。我们引入了编码HSP-16的基因的额外拷贝，这在野生型和长寿突变株中都赋予了胁迫抗性和寿命。hsp-16转录因子对于hsp-16的最大表达和由hsp-16赋予的寿命延长是必需的。这表明，寿命部分是由分子伴侣的胰岛素样调节决定的。
Insulin-like signalling is a key determinate of lifespan in diverse species including mammals but the mechanism by which this pathway influences the rate of aging is unknown. In the roundworm Caenorhabditis elegans, mutations in the insulin-like signalling pathway extend adult lifespan and are associated with up-regulation of stress response genes including those for heat shock proteins (HSPs). We tested the hypothesis that the C. elegans insulin-like signalling pathway determines longevity through modulating HSP levels. We introduced extra copies of the gene encoding HSP-16 and this conferred stress resistance and longevity both in a wildtype and a long-lived mutant strain. The DAF-16 transcription factor is essential for maximal hsp-16 expression and for lifespan extension conferred by hsp-16. This demonstrates that lifespan is determined in part by insulin-like regulation of molecular chaperones.