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

Authors: Zuin A; Carmona M; Morales-Ivorra I; Gabrielli N; Vivancos AP; Ayté J; Hidalgo E

Abstract: 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.

Keywords: Activating Transcription Factor 1/metabolism; Blotting, Northern; Gene Expression Regulation, Fungal; Glucose/pharmacology; Hydrogen Peroxide/pharmacology; Mitogen-Activated Protein Kinases/genetics/*physiology; Oxygen Consumption; Phosphoproteins/metabolism; Phosphorylation/drug effects; Protein-Serine-Threonine Kinases/genetics/physiology; Pyrazoles/pharmacology; Pyrimidines/pharmacology; Schizosaccharomyces/drug effects/genetics/*growth & development/*metabolism; Schizosaccharomyces pombe Proteins/genetics/metabolism/*physiology; Signal Transduction/drug effects/genetics; Stress, Physiological/*physiology
Journal: The EMBO journal
Volume: 29
Issue: 5
Pages: 981-91
Date: Jan. 16, 2010
PMID: 20075862
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Citation:

Zuin A, Carmona M, Morales-Ivorra I, Gabrielli N, Vivancos AP, Ayté J, Hidalgo E (2010) Lifespan extension by calorie restriction relies on the Sty1 MAP kinase stress pathway. The EMBO journal 29: 981-91.


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