title: The role of mitochondria in mTOR-regulated longevity.
abstract: Several unbiased genome-wide RNA interference (RNAi) screens have pointed to mitochondrial metabolism as the major factor for lifespan regulation. However, conflicting data remain to be clarified concerning the mitochondrial free radical theory of aging (MFRTA). Recently, mTOR (mechanistic target of rapamycin) has been proposed to be the central regulator of aging although how mTOR modulates lifespan is poorly understood. Interestingly, mTOR has been shown to regulate many aspects of mitochondrial function, such as mitochondrial biogenesis, apoptosis, mitophagy and mitochondrial hormesis (mitohormesis) including the retrograde response and mitochondrial unfolded protein response (mito-UPR). Here we discuss the data linking mitochondrial metabolism to mTOR regulation of lifespan, suggesting that hormetic effects may be key to explaining some controversial results regarding the MFRTA. We also discuss the possibility that dysfunction of mitochondrial adaptive responses rather than free radicals per se contributes to the aging process.
authors.affiliation: No.3 People's Hospital, School of Medicine, Shanghai Jiao Tong University, 280 Mohe Road, Shanghai, 201900, China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Wei
authors.forename: Yan-Jie
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Cai
authors.forename: Mang-Hua
authors.initials: MH
authors.lastname: Xu
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D058570:TOR Serine-Threonine Kinases
keywords: ROS; aging; hormesis; mTOR; mitochondria; mitophagy; retrograde; stress; theory; unfolded protein response (UPR)