Apoptosis is induced in aging SV40 T antigen-transformed human fibroblasts through p53- and p21CIP1/WAF1-independent pathways

When comparing SV40 T antigen-transformed human fibroblasts of a younger generation (24 population doubling) and aging stage (58 population doubling), we found that detachment of cells from the culture surface occurred more frequently in aging cells. DNA fragmentation and chromatin condensation which 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 compared to cells of a younger generation. Retinoic acid treatment which can effectively suppress p21 gene expression did not prevent apoptosis. These findings indicate that apoptosis that occurs due to aging-transformed human fibroblasts is mediated through p53- and p21-independent pathways.