Living on the edge: Stress and activation of stress responses promote lifespan extension

Abstract

Oxidative stress constitutes the basis of physio-pathological situations such as neurodegenerative diseases andaging. However, sublethal exposure to toxic molecules such as reactive oxygen species can induce cellular responses thatresult in stress fitness. Studies in Schizosaccharomyces pombe have recently showed that the Sty1 MAP kinase, known tobe activated by hydrogen peroxide and other cellular stressors, plays a pivotal role in promoting fitness and longevity whenit becomes activated by calorie restriction, a situation which induces oxidative metabolism and reactive oxygen speciesproduction [1]. Activation of the MAP kinase by calorie restriction during logarithmic growth induces a transcriptional anti-stress response including genes essential to promote lifespan extension. Importantly enough, the lifespan promotionexerted by deletion of the pka1 or sck2 genes, inactivating the two main nutrient-responsive pathways, is dependent onthe presence of a functional Sty1 stress pathway, since double mutants also lacking Sty1 or its main substrate Atf1 do notdisplay extended viability. In this Research Perspective, we review these findings in relation to previous reports andextend important aspects of the original study. We propose that moderate stress levels that are not harmful for cells canmake them stronger. © Zuin et al.