Lifespan extension by calorie restriction relies on the Sty1 MAP kinase stress pathway

Zuin, Alice, 1978-Carmona, MercèMorales Ivorra, IsabelGabrielli, Natalia, 1978-Vivancos Prellezo, AnaAyté del Olmo, JoséHidalgo Hernando, Elena2012-02-152012-02-152010Zuin A, Carmona M, Morales-Ivorra I, Gabrielli N, Vivancos A P, Ayté J, Hidalgo E. Lifespan extension by calorie restriction relies on the Sty1 MAP kinase stress pathway. EMBO Journal. 2010;29:981-91. DOI: 10.1038/emboj.2009.4070261-4189http://hdl.handle.net/10230/16236Either 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 life-span extension in fission yeast, and that such effect is dependent on the activation of the stress-dependent Sty1 MAP kinase. During transition to stationary phase in glucose-limiting conditions, Sty1 becomes activated and triggers a transcriptional stress program, 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 life span 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 life-span extension.application/pdfeng© 2010 European Molecular Biology Organization. Rights Managed by Nature Publishing Group.Proteïnes quinasesCèl·lules -- EnvellimentEstrès oxidatiuLifespan extension by calorie restriction relies on the Sty1 MAP kinase stress pathwayinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/emboj.2009.407MAP kinaseAgingOxidative stressProtein kinase ASty1info:eu-repo/semantics/openAccess