RRC ID 53475
Author Cai Y, Wei YH.
Title Stress resistance and lifespan are increased in C. elegans but decreased in S. cerevisiae by mafr-1/maf1 deletion.
Journal Oncotarget
Abstract Maf1 is a conserved effector of the mechanistic target of rapamycin (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 (UPRmt) and autophagy. mafr-1 deletion also attenuates the paralysis of a C. elegans model of Alzheimer's disease. Our study reveals distinct mechanisms of lifespan regulation by Maf1 and MAFR-1.
Volume 7(10)
Pages 10812-26
Published 2016-3-8
DOI 10.18632/oncotarget.7769
PII 7769
PMID 26934328
PMC PMC4905441
MeSH Animals Autophagy Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Caloric Restriction Humans Longevity / genetics Repressor Proteins / deficiency Repressor Proteins / genetics Repressor Proteins / metabolism Saccharomyces cerevisiae / genetics Saccharomyces cerevisiae / physiology* Saccharomyces cerevisiae Proteins / genetics Saccharomyces cerevisiae Proteins / metabolism Transcription Factors / deficiency* Transcription Factors / genetics Transcription Factors / metabolism
IF 5.168
Times Cited 20
C.elegans tm6028 tm6082