RNA-mediated epigenetic regulation in exercised heart: Mechanisms and opportunities for intervention

Physical exercise has been widely acknowledged as a beneficial lifestyle alteration and a potent non-pharmacological treatment for heart disease. Extensive investigations have revealed the beneficial effects of exercise on the heart and the underlying mechanisms involved. Exercise is considered one of the key factors that can lead to epigenetic alterations. The increasing number of identified molecules in the exercised heart has led to many studies in recent years that have explored the cellular function of ncRNAs and RNA modifications in the heart. Investigating the regulatory role of RNA-mediated epigenetic regulation in exercised hearts will contribute to the development of therapeutic strategies for the management of heart diseases. This review aims to summarize the positive impact of exercise on cardiac health. We will first provide an overview of the mechanisms through which exercise offers protection to the heart. Subsequently, we will delve into the current understanding of ncRNAs, specifically miRNAs, lncRNAs, and circRNAs, as well as RNA modification, focusing on RNA m⁶A and RNA A-to-I editing, and how they contribute to exercise-induced benefits for the heart. Lastly, we will explore the emerging therapeutic strategies that utilize exercise-mediated RNA epigenetic regulation in the treatment of heart diseases, while also addressing the challenges faced in this field.