In vitroreplicative senescence is characterized by an irreversible growth arrest due to the inability of the cell to induce some key regulators of cell cycle progression, such as c-fos and AP-1, in response to mitogenic stimuli.In vitroreplicative senescence andin vivoaging have been assumed to be two related phenomena, likely controlled by overlapping or interacting genes. As a corollary, fibroblasts from centenarians, which have undergone a long process of senescencein vivoshould have very limited proliferative capability. On the contrary, in a previous work we found that fibroblasts from centenarians exhibited the same capacity to respond to different mitogenic stimuli as fibroblasts from young donors. Here we provide evidences that the well preserved proliferative response is likely due to the fact that some pivotal regulators—c-fos, c-jun and AP-1—are still fully inducible, despite a long procss ofin vivosenescence. Our data therefore suggest thatin vivoandin vitroaging are separate phenomena whose possible relationships, if any, have to be ascertained very carefully.