Significance: Heart failure is often accompanied by a decrease in the number of cardiomyocytes. Although the adult mammalian hearts have limited regenerative capacity, the rate of regeneration is extremely low and decreases with age. Exercise is an effective means to improve cardiovascular function and prevent cardiovascular diseases. However, the molecular mechanisms of how exercise acts on cardiomyocytes are still not fully elucidated. Therefore, it is important to explore the role of exercise in cardiomyocytes and cardiac regeneration. Recent Advances: Recent advances have shown that the effects of exercise on cardiomyocytes are critical for cardiac repair and regeneration. Exercise can induce cardiomyocyte growth by increasing the size and number. It can induce physiological cardiomyocyte hypertrophy, inhibit cardiomyocyte apoptosis, and promote cardiomyocyte proliferation. In this review, we have discussed the molecular mechanisms and recent studies of exercise-induced cardiac regeneration, with a focus on its effects on cardiomyocytes. Critical Issues: There is no effective way to promote cardiac regeneration. Moderate exercise can keep the heart healthy by encouraging adult cardiomyocytes to survive and regenerate. Therefore, exercise could be a promising tool for stimulating the regenerative capability of the heart and keeping the heart healthy. Future Directions: Although exercise is an important measure to promote cardiomyocyte growth and subsequent cardiac regeneration, more studies are needed on how to do beneficial exercise and what factors are involved in cardiac repair and regeneration. Thus, it is important to clarify the mechanisms, pathways, and other critical factors involved in the exercise-mediated cardiac repair and regeneration. Antioxid. Redox Signal. 39, 1088-1107.
Keywords: cardiac regeneration; cardiac repair; cardio-protection; cardiomyocyte proliferation; exercise.