Effects of donor age on the expression of a marker of replicative senescence (EPC-1) in human dermal fibroblasts

EPC-1 (early population doubling level cDNA-1) isa quiescence-specific gene expressed at high levels by early passage WI-38 fibroblasts under conditio ns of either density-dependent growth arrest or serum deprivation. Late pas sage WI-38 cells lose the ability to express EPC-1 under all conditions tes ted. The decline in EPC-1 mRNA is gradual during the replicative life span and correlates inversely with the population doubling level (PDL) of the ce lls. The objective of this study was to determine whether the decline in EP C-1 mRNA abundance observed during proliferative senescence also occurs in cultures derived from donors of different ages. To address this question, w e examined the abundance of EPC-1 mRNA in 28 skin fibroblast lines establis hed from healthy donors of different ages ranging from 12 fetal weeks to 94 years. EPC-1 expression was measured, under conditions of growth arrest, p rior to the end of the replicative life span of the cultures. Despite some variability in steady-state transcript levels among the cell lines, EPC-1 e xpression was significantly lower in cells derived from the fetal donor gro up (12-20 gestational weeks) than in cells derived from adult donors. An in vitro age-dependent decline in EPC-1 expression was observed in all the sk in lines examined, independent of donor age; however, no significant differ ence was observed between the young adult donor group (17-33 years) and the old adult donor group (78-94 years). Thus, expression of EPC-1 is linked t o the replicative age of the cells and whether the cells are derived from f etal skin or adult skin. In adults, EPC-1 expression is independent of dono r age. J. Cell. Physiol. 179:11-17, 1999. (C) 1999 Wiley-Liss, Inc.