Relation between maximum replicative capacity and oxidative stress-induced responses in human skin fibroblasts in vitro

Abstract

Cellular senescence, an important factor in ageing phenotypes, can be induced by replicative exhaustion or by stress. We investigated the relation between maximum replicative capacity, telomere length, stress-induced cellular senescence, and apoptosis/cell death in human primary fibroblast strains obtained from nonagenarians of the Leiden 85-plus Study. Fibroblast strains were cultured until replicative senescence and stressed with rotenone at low passage. Telomere length, senescence-associated-β-galactosidase activity, sub-G1 content, and Annexin-V/PI positivity were measured in nonstressed and stressed conditions. Fibroblast strains with a higher replicative capacity had longer telomeres (p =.054). In nonstressed conditions, replicative capacity was not associated with β-gal activity (p =.07) and negatively with sub-G1 (p =.008). In rotenone-stressed conditions, replicative capacity was negatively associated with β-gal activity (p =.034) and positively with sub-G1 (p =.07). Summarizing, fibroblast strains with a higher maximum replicative capacity have longer telomeres, are less prone to go into stress-induced cellular senescence, and more prone to die after stress. © The Author 2010.