C-FOS C-JUN EXPRESSION AND AP-1 ACTIVATION IN SKIN FIBROBLASTS FROM CENTENARIANS/

In vitro replicative senescence is characterized by an irreversible gr owth arrest due to the inability of the cell to induce some key regula tors of cell cycle progression, such as c-fos and AP-1, in response to mitogenic stimuli. In vitro replicative senescence and in vivo aging have been assumed to be two related phenomena, likely controlled by ov erlapping or interacting genes. As a corollary, fibroblasts from cente narians, which have undergone a long process of senescence in vivo sho uld have very limited proliferative capability. On the contrary, in a previous work we found that fibroblasts from centenarians exhibited th e same capacity to respond to different mitogenic stimuli as fibroblas ts from young donors. Here we provide evidences that the well preserve d proliferative response is likely due to the fact that some pivotal r egulators-c-fos, c-jun and AP-1-are still fully inducible, despite a l ong procss of in vivo senescence. Our data therefore suggest that in v ivo and in vitro aging are separate phenomena whose possible relations hips, if any, have to be ascertained very carefully. (C) 1996 Academic Press, Inc.