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Exp Gerontol. 2020 Mar;131:110824. doi: 10.1016/j.exger.2019.110824. Epub 2020 Jan 3.

The intersection of exercise and aging on mitochondrial protein quality control.

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School of Sports and Health, Nanjing Sport Institute, Nanjing, Jiangsu, China.
Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario M3J 1P3, Canada.
Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario M3J 1P3, Canada. Electronic address:


Skeletal muscle quality and quantity are negatively impacted with age. Part of this decline in function can be attributed to alterations in mitochondrial turnover, and in the mechanisms that regulate mitochondrial homeostasis. Protein quality control within the mitochondria relies on a number of interconnected processes, namely the mitochondrial unfolded protein response (UPRmt), protein import and mitophagy. In particular, the post-transcriptional regulation of protein import into the organelle has generated considerable recent interest in view of its dynamic versatility. The capacity for import can be increased by chronic exercise, and diminished by muscle disuse, and defects in the import pathway can be rescued by exercise. Within mitochondria, the unfolded protein response (UPR) is activated if protein import is altered, or if protein misfolding takes place. This UPR generates retrograde signaling to the nucleus to activate compensatory gene expression and protein synthesis. Mitophagy is also elevated with age, contributing to the lower mitochondrial content in aging muscle. However, mitophagy is amenable to exercise adaptations, as it is activated with each exercise bout, presumably to mediate mitochondrial quality control. However, this response is attenuated in older subjects. Although not yet completely elucidated, numerous molecular processes involved in mitochondrial biogenesis and turnover are affected with age. The contrasting and often opposite consequences of exercise and age suggest that exercise can serve as non-pharmacological "mitochondrial medicine" for aging muscle to ameliorate mitochondrial content and function, via pathways that implicate organelle protein quality control mechanisms.


Mitochondrial unfolded protein response; Mitophagy; Protein import; Sarcopenia; Training

Conflict of interest statement

Declaration of competing interest The authors are not aware of any affiliations, memberships, funding or financial holdings that might be perceived as affecting the objectivity of this review.

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