Regulatory Mechanisms of Mitochondrial Function and Cardiac Aging

Aging is a major risk factor for cardiovascular diseases (CVDs), the major cause of death worldwide. Cardiac myocytes, which hold the most abundant mitochondrial population, are terminally differentiated cells with diminished regenerative capacity in the adult. Cardiomyocyte mitochondrial dysfunction is a characteristic feature of the aging heart and one out of the nine features of cellular aging. Aging and cardiac pathologies are also associated with increased senescence in the heart. However, the cause and consequences of cardiac senescence during aging or in cardiac pathologies are mostly unrecognized. Further, despite recent advancement in anti-senescence therapy, the targeted cell type and the effect on cardiac structure and function have been largely overlooked. The unique cellular composition of the heart, and especially the functional properties of cardiomyocytes, need to be considered when designing therapeutics to target cardiac aging. Here we review recent findings regarding key factors regulating cell senescence, mitochondrial health as well as cardiomyocyte rejuvenation.