Autophagy is the name given to a collection of processes responsible for recycling damaged or otherwise unwanted structures and proteins in the cell. With age, autophagy becomes less efficient. Many individual mechanisms falter, and the end result is that cells become more cluttered with damaged parts and harmful proteins. Scaled up across entire organs, this has a meaningful contribution to the progression of aging and age-related disease. Interestingly, increased or more efficient autophagy appears to be a centrally important mechanism in the benefits to health and longevity provided by calorie restriction and a range of other interventions that mildly stress cells. Accordingly, there is a great deal of interest in the research community in developing therapies based on upregulation of autophagy, though progress towards the clinical has been quite slow so far.

Regular exercise training helps to improve the body’s metabolism. The protective effect of exercise on the cardiovascular system has been increasingly recognized in recent years. Exercise can improve the level of cardiac autophagy, promote cardiomyocytes proliferation, reduce local tissue inflammation, and improve cardiac function. Cardiac autophagy plays a crucial role in exercise-induced cardioprotection as a stress response and is a necessary process for adaptation to exercise. However, there are still many questions to be answered in the study of the protective effects and mechanisms of autophagy as they relate to exercise training.

Exercise training for regulating autophagy can be bidirectional. Autophagy impairment and altered autophagy levels have been implicated in the pathogenesis of many diseases. Insufficient autophagy has been reported to contribute to multiple organ dysfunction and other adverse outcomes in autophagy-deficient mice as well as in ill patients, with an observed autophagy deficiency phenotype, evidenced by impaired autophagosome formation, accumulation of damaged proteins and mitochondria, and so on. Excessive autophagy characterized by lysosomal defects and an accumulation of autophagic vacuoles can play an important role in X-linked myopathy. Specifically, for cardiovascular diseases caused by insufficient autophagy, exercise training up-regulates autophagy. For cardiovascular disease caused by excessive autophagy, exercise training can inhibit autophagy, restore regular autophagy function, and delay the progression of cardiovascular disease.

Autophagy is critical in the maintenance of mitochondrial quality and oxidative stress during cardiovascular stress, while exercise can restore protein quality and increase the clearance of reactive aldehydes. Moreover, an increased basal level of cardiac autophagy improves myocardium resistance to subsequent ischemic injury. Aerobic exercise can inhibit the phosphorylation of mTOR by up-regulating the activity of AMPK, thereby improving cardiomyocytes autophagy and preventing cardiac aging and systolic and diastolic dysfunction. A single bout of exercise can also activate autophagy in the heart by activating the transcription factors FOXO3 and hypoxia-inducible factor 1 and then indirectly up-regulating Beclin 1 expression.