Apoptosis is induced in aging SV40 T antigen-transformed human fibroblaststhrough p53- and p21(CIP1/WAF1)-independent pathways

When comparing SV40 T antigen-transformed human fibroblasts of a younger ge neration (24 population doubling) and aging stage (58 population doubling), we found that detachment of cells from the culture surface occurred more f requently in aging cells. DNA fragmentation and chromatin condensation whic h are typical findings of apoptosis occurred more frequently in aging cells as compared to cells of a younger generation. There is no increase in the p53 level or decrease in the SV40 T antigen level in aging cells as compare d to cells of a younger generation. Retinoic acid treatment which can effec tively suppress p21 gene expression did not prevent apoptosis. These findin gs indicate that apoptosis that occurs due to aging-transformed human fibro blasts is mediated through p53- and p21-independent pathways. (C) 1998 Else vier Science Ireland Ltd. All rights reserved.