Fndc5/irisin mediates the benefits of aerobic exercise intervention on aging-associated sarcopenia in mice.

Abstract

Methods: In this study, 24-month-old (aged) mice were used as a naturally occurring model of aging-associated sarcopenia, while 2-month-old (young) mice served as the normal control. Six weeks of treadmill training was employed as an aerobic exercise intervention. The mRNA and protein levels of fibronectin type III domain-containing protein 5 (Fndc5/irisin), MuRF1, and Atrogin-1 in gastrocnemius muscles were analyzed using qRT-PCR and Western blot. Oxidative stress was assessed using relevant detection kits. Skeletal muscle function was evaluated through the four-paw hanging test, rotarod test, grip strength assay, and measurements of quadriceps, tibialis anterior, and gastrocnemius muscle mass.

Results: Aerobic exercise interventions enhanced skeletal muscle function by increasing hanging time, maximum speed, grip strength, and increased quadriceps, gastrocnemius, and tibialis anterior muscle mass. On the other hand, aerobic exercise reduced MuRF1 and Atrogin-1 expression in the gastrocnemius muscles of sarcopenia mice, along with lower malondialdehyde levels, and higher superoxide dismutase activity, T-ATPase, and glutathione peroxidase activity. A decline in Fndc5/irisin expression was further detected in the gastrocnemius muscles with aging. In Fndc5-knockout aged mice, aerobic exercise failed to improve skeletal muscle function compared to wild-type aged mice, as evaluated by hanging time, grip strength, maximum speed, and quadriceps, gastrocnemius, and tibialis anterior muscle mass, further validating the involvement of Fndc5 in the improvement of aging-associated sarcopenia.

Conclusion: Aerobic exercise improves aging-associated sarcopenia in mice, with Fndc5/irisin playing a role in this process.