Effect of aging on resistance to oxidative stress in human endothelial progenitor cells (EPCs)

Abstract

The role of oxidative stress and antioxidant enzymes in the aging related dysfunction of EPCs has not been studied. We hypothesized that impaired antioxidant capacity contributes to dysfunction of EPCs. Early EPCs isolated from healthy young (24±3 year-old, n=9) and aged (71±5 year-old, n=9) males were examined. The levels of protein expression and enzymatic activity of glutathione peroxidase 1 (GPX1) were decreased significantly in the EPCs from aged individuals in compared to EPCs from young individuals (n=9, P<0.05). After 24 h of serum starvation EPC numbers in young group and aged group were 0.6±0.2 and 0.4±0.1, respectively (expressed as ratio to the cell number under normal culture conditions, n=6, P<0.05). H2O2 (1mM) treatment for 24 h significantly decreased EPC number to 37±13% in aged, compared with young individuals (67±13%, n=3, P<0.05). Furthermore, under normal culture conditions the numbers of senescent β-galactosidase (β-gal) positive EPCs were not significantly different between young and aged subjects (46.1±8.4%, and 58.3±7.6, respectively, n=3). However, H2O2 (50 μM) treatment significantly increased the β-gal positive cells in aged EPCs (73±9%), compared with young EPCs (43±11%, n=3, P<0.05). These results suggest that EPCs of older individuals are more susceptible to oxidative stress induced by H2O2 and serum starvation, resulting in decreased survival and increased senescence. Reduced expression of GPX1 may contribute to EPC dysfunction with aging.