**12. Senescence and cancer**

We have already mentioned that strong p53 activation induces apoptosis. However, Leontieva and colleagues have shown that a weak and sustained p53 activation during cell cycle arrest can promote a different type of cell demise known as **senescence** [133]. Cellular senescence, induced after an irreversible cell cycle arrest, is a protective mechanism that limits proliferation of cells exposed to endogenous or exogenous insults. This cell death type can take part in processes of tumour suppression, tumour promotion, aging, and tissue repair [134]. Senescent cells become flattened and enriched with vacuoles. Some of the biochemical changes characteristic of senescence include elevation in β-galactosidase activity at an acidic pH, increase in senescence markers (p16, p15, p21, p53, ARF, etc.), heterochromatinization and, similarly to autophagy, formation of autolysosomes. It has been recently shown that chemotherapeutic agents may cause a form of "premature senescence" that can be considered as a tumour suppressor mechanism. Therefore, the induction of premature senescence as a drug-inducible arrest program has therapeutic potential for cancer treatment, but requires further investigation [135].
