Health benefits of physical activity: What role does skeletal muscle-organ crosstalk play?

The observation that physical activity (PA) reduces the risk of coronary heart disease dates back more than 70 years ago and it is now established that regular PA reduces all-cause mortality, in part, by reducing the risk of numerous chronic diseases including coronary heart disease, stroke, cancer, type 2 diabetes, and Alzheimer's disease. During the past decade the increased use of activity tracking devices has significantly improved our understanding of the dose-response relationships between PA and all-cause mortality. Further, our appreciation of the impact that prolonged sitting has on all-cause mortality has increased. Moreover, new research provides key insight into the signaling mechanisms that connect PA to the reduced risk of disease in multiple organ systems. Therefore, given the recent advances in the study of PA and all-cause mortality, it is an appropriate time to review the latest evidence on this topic as well as the mechanisms responsible for the PA-induced protection against all-cause mortality. Therefore, this review will summarize recent data on the dose-response association between PA on all-cause mortality and the negative impact that sedentary behavior has on all-cause mortality. Further, we also highlight potential mechanisms linking PA with the reduced risk of developing several chronic diseases. Finally, we conclude with a brief discussion of the emerging evidence that the health benefits associated with PA are derived, in part, from skeletal muscle-organ crosstalk involving muscle produced hormones (myokines) that exert their effects in either an autocrine, paracrine, or endocrine manner.