[Mechanisms and medical implications of replicative senescence]

Normal somatic cells divide in vitro only for a limited number of times, and then enter a state of replicative senescence. In most human cells replicative senescence is triggered by critical shortening and uncapping of telomeres, which leads to the up-regulation of p53 and/or p16 suppressor proteins that inhibit cell divisions. Because both reconstruction of telomeres and inactivation of suppressor proteins enables the cells to grow further or even immortalize, it has been hypothesized that replicative senescence acts as a natural barrier against neoplastic transformation. On the other hand, however, recent reports suggest that the accumulation of senescent cells may jeopardize tissue integrity and create a specific microenvironment that promotes tumorogenesis in elderly people. In this review we describe recent advances in our knowledge on the mechanisms of replicative senescence and discuss its medical implications.