Several molecular pathways are implicated in the induction of replicative senescence, most notably the p53 and Rb pathways. The p53 protein is a tumor suppressor that can initiate senescence in response to DNA damage, including critically short telomeres. The Rb pathway also contributes to cell cycle arrest by inhibiting the activity of E2F transcription factors essential for DNA synthesis. Mutations in these pathways are common in many cancers, allowing cells to evade senescence.
