Control of muscle satellite cell function by specific exercise-induced cytokines and their applications in muscle maintenance

Abstract

Exercise is recognized to play an observable role in improving human health, especially in promoting muscle hypertrophy and intervening in muscle mass loss-related diseases, including sarcopenia. Recent rapid advances have demonstrated that exercise induces the release of abundant cytokines from several tissues (e.g., liver, muscle, and adipose tissue), and multiple cytokines improve the functions or expand the numbers of adult stem cells, providing candidate cytokines for alleviating a wide range of diseases. Muscle satellite cells (SCs) are a population of muscle stem cells that are mitotically quiescent but exit from the dormancy state to become activated in response to physical stimuli, after which SCs undergo asymmetric divisions to generate new SCs (stem cell pool maintenance) and commit to later differentiation into myocytes (skeletal muscle replenishment). SCs are essential for the postnatal growth, maintenance, and regeneration of skeletal muscle. Emerging evidence reveals that exercise regulates muscle function largely via the exercise-induced cytokines that govern SC potential, but this phenomenon is complicated and confusing. This review provides a comprehensive integrative overview of the identified exercise-induced cytokines and the roles of these cytokines in SC function, providing a more complete picture regarding the mechanism of SC homeostasis and rejuvenation therapies for skeletal muscle.

Keywords: Cytokines; Exercise; Homeostasis; Muscle satellite cells; Skeletal muscle.

Figure 1

Overview of the exercise‐induced cytokines regulating SCs. Exercise induces the release of cytokines, including myokines, hepatokines, adipokines, from multiple tissues. These cytokines synergistically induce the activation, proliferation, and differentiation of SCs, with enhanced self‐renewal to preserve the SC pool. Specific exercise‐induced cytokines are critical mediators of exercise in muscle hypertension and have high therapeutic potential against muscle loss.