Aging and Oxidative Stress Resistance in Human Fibroblasts

Abstract

Alterations in the oxidative stress resistance of human embryonic lung fibroblasts during aging in vitro and human skin fibroblasts during aging in vivo were examined. Human embryonic lung fibroblasts were serially cultivated, and early- and late-passage cells were used as young and old cells in vitro, respectively. On the other hand, human skin fibroblasts were obtained from young and old donors, and young and old donor’s cells were used as young and old cells in vivo, respectively. Resistance of late-passage cells to oxidative stress caused by hydrogen peroxide, linoleic acid hydroperoxide, or a hypoxanthine-xanthine oxidase system decreases as compared with early-passage cells. Reduced glutathione concentration and catalase activity are lower in late-passage cells than in early-passage cells. The in vitro life span of human embryonic lung fibroblasts is perturbed by oxidative stress. The life span extends and shortens depending on an increase and decrease, respectively, in cellular reduced glutathione concentration. In addition, it shortens by treatment of either hyperbaric oxygen or the catalase inhibitor 3-amino-1H-1,2,4-triazole. On the other hand, resistance of old donor’s skin fibroblasts to oxidative stress caused by hydrogen peroxide, linoleic acid hydroperoxide, or ultraviolet light B is enhanced as compared with young donor’s fibroblasts. Glutathione peroxidase activity is much higher in old donor’s cells than in young donor’s cells. These results suggest that human fibroblasts become resistant to oxidative stress during aging in vivo, while they become vulnerable during aging in vitro, and that their primary defense against oxidative stress appears to be the reduced glutathione-glutathione peroxidase system.