The role of mitochondria in mTOR-regulated longevity

被引:43
作者
Wei, Yuehua [1 ]
Zhang, Yan-Jie [1 ]
Cai, Ying [1 ]
Xu, Mang-Hua [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 3, Shanghai 201900, Peoples R China
基金
中国国家自然科学基金;
关键词
mTOR; aging; mitochondria; ROS; hormesis; retrograde; mitophagy; stress; theory; unfolded protein response (UPR); CHRONOLOGICAL LIFE-SPAN; HYDROGEN-PEROXIDE PRODUCTION; RTG-DEPENDENT MITOCHONDRIA; FREE-RADICAL GENERATION; SYSTEMATIC RNAI SCREEN; LONGEST-LIVING RODENT; SUPEROXIDE-DISMUTASE; CAENORHABDITIS-ELEGANS; MAMMALIAN TARGET; GENE-EXPRESSION;
D O I
10.1111/brv.12103
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:167 / 181
页数:15
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