Universitat Pompeu Fabra, Barcelona, Spain.
EMBO J. 2010 Mar 3;29(5):981-91. doi: 10.1038/emboj.2009.407. Epub 2010 Jan 14.
Either calorie restriction, loss-of-function of the nutrient-dependent PKA or TOR/SCH9 pathways, or activation of stress defences improves longevity in different eukaryotes. However, the molecular links between glucose depletion, nutrient-dependent pathways and stress responses are unknown. Here, we show that either calorie restriction or inactivation of nutrient-dependent pathways induces lifespan extension in fission yeast, and that such effect is dependent on the activation of the stress-dependent Sty1 mitogen-activated protein (MAP) kinase. During transition to stationary phase in glucose-limiting conditions, Sty1 becomes activated and triggers a transcriptional stress programme, whereas such activation does not occur under glucose-rich conditions. Deletion of the genes coding for the SCH9-homologue, Sck2 or the Pka1 kinases, or mutations leading to constitutive activation of the Sty1 stress pathway increase lifespan under glucose-rich conditions, and importantly such beneficial effects depend ultimately on Sty1. Furthermore, cells lacking Pka1 display enhanced oxygen consumption and Sty1 activation under glucose-rich conditions. We conclude that calorie restriction favours oxidative metabolism, reactive oxygen species production and Sty1 MAP kinase activation, and this stress pathway favours lifespan extension.
无论是卡路里限制、营养依赖的 PKA 或 TOR/SCH9 途径的失活，还是应激防御的激活，都能延长不同真核生物的寿命。然而，葡萄糖耗竭、营养依赖途径和应激反应之间的分子联系尚不清楚。在这里，我们表明，无论是卡路里限制还是营养依赖途径的失活，都能诱导裂殖酵母寿命延长，而这种效应依赖于应激依赖的 Sty1 有丝分裂原激活蛋白 (MAP) 激酶的激活。在葡萄糖限制条件下进入静止期时，Sty1 被激活并触发转录应激程序，而在葡萄糖丰富的条件下则不会发生这种激活。SCH9 同源物、Sck2 或 Pka1 激酶的基因缺失，或导致 Sty1 应激途径组成性激活的突变，会在葡萄糖丰富的条件下增加寿命，重要的是，这些有益影响最终取决于 Sty1。此外，缺乏 Pka1 的细胞在葡萄糖丰富的条件下显示出增强的耗氧量和 Sty1 激活。我们得出的结论是，卡路里限制有利于氧化代谢、活性氧的产生和 Sty1 MAP 激酶的激活，而这条应激途径有利于延长寿命。
