Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans
Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans
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DOI：
10.1111/j.1474-9726.2006.00267.x
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发表时间：
2007-02-01
期刊：
影响因子：
7.8
通讯作者：
Kenyon, Cynthia
中科院分区：
文献类型：
--
作者：
Hansen, Malene;Taubert, Stefan;Kenyon, Cynthia
将细胞从营养利用和生长状态转变为细胞维持状态的许多条件延长了寿命。我们对抑制蛋白质合成的条件进行了系统的寿命分析。我们发现，减少核糖体蛋白，核糖体蛋白S6激酶或抑制起始因子的水平增加秀丽隐杆线虫的寿命。这些扰动，以及对雷帕霉素（TOR）的营养传感器靶点的抑制，已知其可以增加寿命，都增加了热应激抗性。因此，抑制翻译可以通过将细胞转移到有利于维护和修复的生理状态来延长寿命。有趣的是，不同类型的翻译抑制导致两种相互排斥的输出之一，一种是通过转录因子β-16/FOXO增加寿命和抗逆性，另一种是独立于β-16增加寿命和抗逆性。我们的发现将TOR而不是sir-2.1与C.他们认为，TOR抑制和DR都不能简单地通过减少蛋白质合成来延长寿命。
Many conditions that shift cells from states of nutrient utilization and growth to states of cell maintenance extend lifespan. We have carried out a systematic lifespan analysis of conditions that inhibit protein synthesis. We find that reducing the levels of ribosomal proteins, ribosomal-protein S6 kinase or translation-initiation factors increases the lifespan of Caenorhabditis elegans. These perturbations, as well as inhibition of the nutrient sensor target of rapamycin (TOR), which is known to increase lifespan, all increase thermal-stress resistance. Thus inhibiting translation may extend lifespan by shifting cells to physiological states that favor maintenance and repair. Interestingly, different types of translation inhibition lead to one of two mutually exclusive outputs, one that increases lifespan and stress resistance through the transcription factor DAF-16/FOXO, and one that increases lifespan and stress resistance independently of DAF-16. Our findings link TOR, but not sir-2.1, to the longevity response induced by dietary restriction (DR) in C. elegans, and they suggest that neither TOR inhibition nor DR extends lifespan simply by reducing protein synthesis.