Aging Induced Senescence of Human Cardiac Progenitor Cells Alters the Healthy Cellular Microenvironment: Implications...

Age-related senescence can profoundly alter the physiology and therapeutic potential of cardiac progenitor cells (CPCs), thus undermining the efficiency of cell-based therapies for treatment of various cardiovascular diseases. In this study, CPCs were isolated from right atrial appendage tissue obtained during open heart surgery from patients: younger (< 30 years, n = 10) and elderly (> 60 years, n = 10). Phenotypic and functional characterization of CPCs was done along with evaluation of age-related senescent changes using various assays. CPCs derived from elderly patients exhibited significantly reduced proliferative potential, enlarged morphology, increased expression of senescence markers (p16^Ink4A, SA β-gal, γH2AX), and significantly higher proportion of cells in the G0/G1 phase of the cell cycle. In addition, aged CPCs showed elevated secretion of senescence associated secretory phenotypes (SASP) factors, particularly IL-8, IL-10, and IFN-γ. Current study observed that a significantly higher (80%) number of CPCs among the older population were senescent, dysfunctional, and in the resting phase of the cell cycle, thus having limited ability to repair the damaged heart. Further, we observed a contradictory increase in Nkx2.5 expression with age, suggesting the reactivation of the cardiac Nkx2.5 enhancer.