The aged heart displays a loss of cardiomyocyte number and function, possibly due to the senescence and decreased regenerative potential that has been observed in some cardiac progenitor cells. An important cardiac progenitor that has not been studied in the context of aging is the cardiac side population (CSP) cell. To address this, flow cytometry-assisted cell sorting was used to isolate CSP cells from adult (6–10 months old) and aged (24–32 months old) C57Bl/6 mice that were fed either a control diet or an anti-aging diet (caloric restriction, CR). Aging caused a 2.3-fold increase in the total number of CSP cells and a 3.2-fold increase in the cardiomyogenic sca1+/CD31− subpopulation. Aging did not affect markers of proliferation or senescence, including telomerase activity and expression of cell cycle genes, in sca1+/CD31− CSP cells. In contrast, the aged cells had reduced expression of genes associated with differentiation, including smooth muscle actin and cardiac muscle actin (5.1- and 3.2-fold, respectively). None of these age effects were altered by CR diet. Therefore, it appears that the manner in which CSP cells age is distinct from the aging of post-mitotic tissue (and perhaps other progenitor cells) that can often be attenuated by CR.

White adipose tissue is a promising source of mesenchymal stem cells. Currently, little is known about the effect of age and caloric restriction (CR) on adipose-derived stem cells (ASC). This is important for three reasons: firstly, age and CR cause extensive remodeling of WAT; it is currently unknown how this remodeling affects the resident stem cell population. Secondly, stem cell senescence has been theorized as one of the causes of aging and could reduce the utility of a stem cell as a reagent. Thirdly, the mechanism by which CR extends lifespan is currently not known, one theory postulates that CR maintains the resident stem cell population in youthful “fit” state. For the purpose of this study, we define ASC as lineage negative (lin−)/CD34+(low)/CD31−. We show that aging increases the abundance of ASC and the expression of Cdkn2a 9.8-fold and Isl1 60.6-fold. This would suggest that aging causes an accumulation of non-replicative ASC. CR reduced the percentage of ASC in the lin− SVF while also reducing colony forming ability. Therefore, CR appears to have anti-proliferative effects on ASC that may be advantageous from the perspective of cancer, but our data raises the possibility that it may be disadvantageous for regenerative medicine applications.