Stress resistance and lifespan are increased in <i>C. elegans</i> but decreased in <i>S. cerevisiae</i> by <i>mafr-1/maf1</i> deletion

// Ying Cai 1 and Yue-Hua Wei 1 1 Shanghai Ninth People&rsquo;s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China Correspondence to: Yue-Hua Wei, email: // Keywords : lifespan, calorie restriction, stress response, autophagy(definition), Maf1, Gerotarget Received : September 24, 2015 Accepted : February 18, 2016 Published : February 26, 2016 Abstract Maf1 is a conserved effector of the mechanistic target of mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">rapamycin(definition) (mTOR), an aging promoting kinase. However, whether Maf1 is required for lifespan extension caused by mTOR inhibition, such as dietary restriction (DR) or calorie restriction (CR) remains elusive. Here we show that deletion of maf1 in the budding yeast S. cerevisiae but not mafr-1 in C. elegans prevents DR or CR to extend lifespan. Interestingly, mafr-1 deletion increases stress tolerance and extends lifespan. MAFR-1 is phosphorylated in a mTOR-dependent manner and mafr-1 deletion alleviates the inhibition of tRNA synthesis caused by reduced mTOR activity. We find that the opposite effect of mafr-1 deletion on lifespan is due to an enhancement of stress response, including oxidative stress response, mitochondrial unfolded protein response (UPR mt ) and autophagy. mafr-1 deletion also attenuates the paralysis of a C. elegans model of Alzheimer&rsquo;s disease. Our study reveals distinct mechanisms of lifespan regulation by Maf1 and MAFR-1.