Human diploid fibroblasts that undergo a senescent-like differentiation have elevated ceramide and diacylglycerol

Senescent human diploid fibroblasts (HDF) have elevated levels of ceramide and diacylglycerol (DAG) compared with young HDF. DNA. fragmentation analys is demonstrated the increased ceramide in senescent HDF was not associated with apoptosis, whereas in young HDF, exogenous ceramide induced apoptosis. In young HDF treated with both exogenous ceramide and DAG, less DNA fragme ntation was observed. Thus, elevated DAG levels in senescent HDF might prot ect against ceramide-induced apoptosis. To determine which characteristics of senescent BDF (aging per se, cell cycle arrest, elevated p21(Sdl1,Waf1,C ip1), and senescent-like differentiation) might influence ceramide and DAG, we examined transformed or mitomycin C-treated HDF that shared some of the se properties with senescent HDF. The elevation of ceramide and DAG did not depend on aging per se, cell cycle arrest, or elevation of p21. Rather, ce ramide and DAG may be elevated as part of a program of differentiation that is induced by either aging or DNA damage.