The epigenetic landscape of exercise in cardiac health and disease

•Exercise induces a profound alteration in epigenetics, which mediates the beneficial effects of exercise.•Exercise not only modifies epigenetics in the heart to promote cardiac health, but also modifies epigenetics in other tissues, which reduces risks of cardiac disease or affords cardioprotection through exerkines.•Exercise-modulated circulating non-coding RNAs are secreted from multiple tissues and shuttled by exosomes, acting as a new kind of exerkine that plays an important role in cardioprotection. With the rising incidence of cardiovascular diseases, the concomitant mortality and morbidity impose huge burdens on quality of life and societal costs. It is generally accepted that physical inactivity is one of the major risk factors for cardiac disease and that exercise benefits the heart in both physiological and pathologic conditions. However, the molecular mechanisms governing the cardioprotective effects exerted by exercise remain incompletely understood. Most recently, an increasing number of studies indicate the involvement of epigenetic modifications in the promotion of cardiac health and prevention of cardiac disease. Exercise and other lifestyle factors extensively induce epigenetic modifications, including DNA/RNA methylation, histone post-translational modifications, and non-coding RNAs in multiple tissues, which may contribute to their positive effects in human health and diseases. In addition, several studies have shown that maternal or paternal exercise prevents age-associated or high-fat diet-induced metabolic dysfunction in the offspring, reinforcing the importance of epigenetics in mediating the beneficial effects of exercise. It has been shown that exercise can directly modify cardiac epigenetics to promote cardiac health and protect the heart against various pathological processes, or it can modify epigenetics in other tissues, which reduces the risk of cardiac disease and affords cardioprotection through exerkines. An in-depth understanding of the epigenetic landscape of cardioprotective response to exercise will provide new therapeutic targets for cardiac diseases. This review, therefore, aimed to acquaint the cardiac community with the rapidly advancing and evolving field of exercise and epigenetics. [Display omitted]