Restoration of Cardiomyogenesis in Aged Mouse Hearts by Voluntary Exercise

BACKGROUND: The human heart has limited capacity to generate new cardiomyocytes,and this capacity declines with age. Because loss of cardiomyocytes may contribute to heart failure, it is crucial to explore stimuli of endogenous cardiac regeneration to favorably shift the balance between loss of cardiomyocytes and the birth of new cardiomyocytes in the aged heart. We have previously shown that cardiomyogenesis can be activated by exercise in the young adult mouse heart. Whether exercise would also induce cardiomyogenesis in aged hearts, however, is yet unknown. Here, we aim to investigate the effect of exercise on generation of new cardiomyocytes in the aged heart.METHODS: Aged (20-months) mice were subjected to an eight-week voluntary running protocol, and age-matched sedentary animals served as controls. Cardiomyogenesis in aged hearts was assessed based on 15N-thymidine incorporation and multi-isotope imaging mass spectrometry (MIMS). We analyzed 1793 cardiomyocytes from five aged sedentary mice and compared these to 2002 cardiomyocytes from five aged, exercised mice followed by advanced histology and imaging to account for ploidy and nucleation status of the cell. RNA sequencing and subsequent bioinformatic analyses were carried out to investigate transcriptional changes induced by exercise specifically in aged heartsin comparison to young hearts.