Reduction of UV-induced cell death in the human senescent fibroblasts

We studied mechanisms by which senescent cells acquire resistance to UV-ind uced cellular insults. Human primary foreskin fibroblast culture was used s ince it undergoes cellular senescence in vitro after a limited number of pa ssages. Senescence was induced by a brief treatment of the early passage ce lls with 100 mu M of H2O2 for 1 h, and subsequent culture for 3 weeks. Hydr ogen peroxide-treated cells showed an enhancement of senescence-associated beta-galactosidase activity. In the senescent cells, DNA fragmentation in r esponse to UV-irradiation was found to decrease significantly compared with that in the young cells, The SAPK/JNK activation by UV irradiation was red uced in both non-treated senescent cells and the hydrogen peroxide-induced senescent cells, suggesting that a reduced DNA fragmentation by UV-irradiat ion in the senescent cells is closely related to the decreased SAPK/JNK act ivity. Since a cell cycle inhibitor, p21(Waf1),has been implicated in prote cting cells against apoptotic cell death, we determined p21(Waf1) to assess whether its elevation has any impact on the reduction of UV-induced activa tion of SAPK/JNK in the senescent cells, The expression of p21(Waf1) increa sed in both the nontreated and the hydrogen peroxide-treated senescent cell s, Our study also revealed that the blockage of SAPK/JNK activation in the senescent cells was closely related to the increased level of p21(Waf1) Our observation might provide clues about molecular mechanism of resistance to DNA fragmentation and the consequent cell death by UV-irradiation.