Aging reduces differentiation‐associated gene expression in cardiac side population cells that is not attenuated by caloric restriction

Abstract

The aged heart displays a loss of cardiomyocyte number and function, possibly due to decreased regenerative potential of cardiac progenitor cells. An important cardiac progenitor population that has not been studied in the context of aging is cardiac side population cells (CSPC). To address this, flow cytometry‐assisted cell sorting was used to isolate CSPC from adult (~5‐months old) and aged (~25‐months old) C57Bl/6 mice that were fed either a control diet or an anti‐aging (caloric restriction, CR) diet. Aging caused a 2.0‐fold increase in both the total number of CSPC and in the highly cardiomyogenic sca1+/CD31‐ subpopulation (n=8–10 mice/group). Telomerase activity (a marker of proliferation) in CSPC was not altered by aging (n=4 mice/group). In contrast, aged CSPC showed reduced expression of several genes associated with differentiation, including smooth muscle actin, cardiac muscle actin, and bone collagen type I (5.1‐, 3.2‐, and 2.2‐fold respectively; n=4/group). These data suggest that any loss of regenerative potential in aged CSPC is likely due to inefficiency of differentiation into cardiac lineages rather than poor proliferation rate. None of these age effects were altered by CR diet. Therefore it appears that the manner in which CSPC (and perhaps other types of progenitor cells) age is distinct from the post‐mitotic tissue aging that can often be attenuated by CR.