Aerobic exercise improve physical endurance and muscle function by ameliorating oxidative stress and modulating mitochondrial dynamics in aged skeletal muscle.

Abstract

Mitochondrial dysfunction is associated with the age-related decline in skeletal muscle mass and strength. Aerobic exercise upregulate Sestrins protein expression in skeletal muscle, which plays a key role in maintaining mitochondrial homeostasis. This study aimed to elucidate the role of aerobic exercise in regulating mitochondrial dynamics and oxidative stress in aging skeletal muscle. We randomly assigned male C57BL/6J mice into four groups: Young Control Group (YC), Young Aerobic Exercise Group (YA), Old Control Group (OC) and Old Aerobic Exercise Group (OA). We confirmed that aerobic exercise significantly enhanced grip strength and running capacity in aged mice compared to the OC group. The OC group exhibited significantly elevated MDA levels in skeletal muscle compared to the YC group, whereas aerobic exercise reduced MDA levels while increasing SOD and CAT activities in exercise group. Compared to the YC group, aging significantly reduced Sestrin1 protein expression, while Sestrin2 and Sestrin3 levels remained unaffected. Notably, aerobic exercise intervention significantly elevated Sestrin1 expression in OA group, compared to OC group, while no observable effects on Sestrin2/3 expression. Additionally Phospho-AMPK (Thr172), and PGC-1α were significantly increased in both the YA and OA groups. Aging also caused a marked decline in SDH activity and an increase in PGAM5 and OPA1 protein levels in the OC group. In addition, aerobic exercise improved SDH activity and augmented MFN2, OPA1 and PINK1 expression in YA and OA groups. In conclusion, aging induces oxidative stress accumulation and mitochondrial dysfunction in skeletal muscle, whereas 8-week of aerobic exercise mitigates these effects by upregulating Sestrin1 and its downstream targets, thus enhancing mitochondrial dynamics and function in aged mice.