Redox Signaling in Widespread Health Benefits of Exercise

Abstract
Significance: Exercise-induced ROS production activates multiple intracellular signaling pathways through genomic and non-genomic mechanisms that are responsible for the beneficial effects of exercise in muscle. Beyond the positive effect of exercise on skeletal muscle cells, other tissues such as white and brown adipose, liver, central nervous system, endothelial, heart and endocrine organ tissues are also responsive to exercise. Recent Advances: Crosstalk between different cells is essential to achieve homeostasis and to promote the benefits of exercise through paracrine or endocrine signaling. This crosstalk can be mediated by different effectors that include the secretion of metabolites of muscle contraction, myokines and exosomes. During the past 20 years, it has been demonstrated that contracting muscle cells produce and secrete different classes of myokines, which functionally link muscle with nearly all other cell types. Critical Issues: The redox signaling behind this exercise-induced crosstalk is now being decoded. Many of these widespread beneficial effects of exercise require not only a complex ROS-dependent intramuscular signaling cascade, but simultaneously, an integrated network with many remote tissues. Future Directions: Strong evidence suggests that the powerful beneficial effect of regular physical activity for preventing (or treating) a large range of disorders might also rely on ROS-mediated signaling. Within a contracting muscle, ROS signalling may control exosomes and myokines secretion. In remote tissues, exercise generates regular and synchronized ROS waves, creating a transient pro-oxidative environment in many cells. These new concepts integrate exercise, ROS-mediated signalling and the widespread health benefits of exercise.