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

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.

Role of Oxidative Stress Response and Trehalose Accumulation in the Longevity of Fission Yeast

“…On the other hand, Sanchez-Fresneda et al (33) reported that the stress-induced trehalose accumulation is Hog1-independent in Candida albicans. The extension of lifespan in S. pombe is associated with both calorie restriction and increased resistance to oxidative stress (10)(11)(12). Chiming in with a study done on S. cerevisiae by Mahmud et al (34), our results suggest that lifespan extension in S. pombe may not be associated with oxidative stress resistance and trehalose accumulation.…”

Genes involved in glucose repression and oxidative stress response in the fission yeast Schizosaccharomyces pombe

“…Additionally, glucose sensing and signaling regulates the increased expression of various stress response genes through the activation of the Atf1p and Pap1p transcription factors in S. pombe (Madrid et al, 2004;Stiefel et al, 2004). The activation of a Sty1 MAP kinase by calorie restriction participates in life span extension, which was shown for the first time by Zuin et al, (2010). In the same study, it was reported that either low-glucose media or activation of the nutrient-dependent Pka1 pathway promoted life span extension in fission yeast, including high respiratory rates, elevated ROS production, activation of the MAP kinase Sty1 pathway and expression of survival genes.…”

Cells Lacking Pfh1, a Fission Yeast Homolog of Mammalian Frataxin Protein, Display Constitutive Activation of the Iron Starvation Response

“…Measurement of Oxygen Consumption-Oxygen consumption of ϳ10 7 cells in 1 ml, collected from anaerobic cultures at an A 600 of 0.5, was measured as described before (35).…”