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The role of mitochondria in mTOR ‐regulated longevity
Author(s) -
Wei Yuehua,
Zhang YanJie,
Cai Ying,
Xu MangHua
Publication year - 2015
Publication title -
biological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.993
H-Index - 165
eISSN - 1469-185X
pISSN - 1464-7931
DOI - 10.1111/brv.12103
Subject(s) - mitophagy , mitochondrial biogenesis , mitochondrion , pi3k/akt/mtor pathway , biology , microbiology and biotechnology , hormesis , longevity , mechanistic target of rapamycin , biogenesis , regulator , mtorc2 , rna interference , autophagy , mitochondrial dna , genetics , rna , signal transduction , mtorc1 , apoptosis , oxidative stress , biochemistry , gene
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.