Parkin overexpression protects from aging‐related loss of muscle mass and strength

Key points

Recent evidence suggests that impaired mitophagy, a process in charge of removing damaged/dysfunctional mitochondria and in part regulated by Parkin, could contribute to the aging‐related loss of muscle mass and function. Here, we show that parkin overexpression attenuates aging‐related loss of muscle mass and strength and unexpectedly causes hypertrophy in adult skeletal muscles. We also show that Parkin overexpression leads to increases in mitochondrial content and enzymatic activities. Finally, our results show that Parkin overexpression protects from aging‐related increases in markers of oxidative stress, fibrosis and apoptosis. Our findings place Parkin as a potential therapeutic target to attenuate sarcopenia and improve skeletal muscle health and performance. The aging‐related loss of muscle mass and strength, a process called sarcopenia, is one of the most deleterious hallmarks of aging. Solid experimental evidence indicates that mitochondrial dysfunctions accumulate with aging and are critical in the sarcopenic process. Recent findings suggest that mitophagy, the process in charge of the removal of damaged/dysfunctional mitochondria, is altered in aged muscle. Impaired mitophagy represents an attractive mechanism that could contribute to the accumulation of mitochondrial dysfunctions and sarcopenia. To test this hypothesis, we investigated the impact of Parkin overexpression in skeletal muscles of young and old mice. Parkin was overexpressed for 4 months in muscles of young (3mo) and late middle‐aged (18mo) mice using intramuscular injections of Adeno‐Associated Viruses. We show that Parkin overexpression increased muscle mass, fiber size and mitochondrial enzyme activities in both young and old muscles. In old mice, Parkin overexpression increased muscle strength, PGC‐1α content and mitochondrial density. Parkin overexpression also attenuated the aging‐related increase in 4‐hydroxynonenal content (a marker of oxidative stress), type I collagen content (a marker of fibrosis) and in the number of TUNEL‐positive myonuclei (a marker of apoptosis). Overall, our results indicate Parkin overexpression attenuates sarcopenia and unexpectedly causes hypertrophy in adult muscles. They also show that Parkin overexpression leads to increases in mitochondrial content and enzymatic activities. Finally, our results show that Parkin overexpression protects against oxidative stress, fibrosis and apoptosis. These findings highlight that Parkin may be an attractive therapeutic target to attenuate sarcopenia and improve skeletal muscle health and performance.

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