Molecular Mechanisms of Cellular Senescence

Normal mammalian cells in culture have a limited life span and will eventually maintain a growth arrested state, referred to as replicative senescence. Usually induced by telomere shortening this form of arrest is irreversible in the sense that cells cannot be triggered to reenter proliferation by physiological mitotic stimuli like growth factors. Senescence may also occur prematurely in response to various stress stimuli such as oxidative stress, DNA dam‐ age or active oncogenes. Thereby premature senescence acts as an important tumor suppres‐ sive mechanism and not surprisingly there is emerging evidence that senescence is indeed not only a result of tissue culture but markers of senescence have been identified in vivo in human and animal tissue.