Cellular senescence plays an important role in normal aging, as well as in age-related diseases. Impaired cellular senescence contributes to malignant transformation and cancer development. Presence of an excessive number of senescent cells that are not cleared by the immune system, however, promotes tissue inflammation and creates a microenvironment suitable for growth of neighboring malignant cells. Besides cancer, senescence is also involved in atherosclerosis, osteoarthritis and diabetes (Childs et al. 2015, He and Sharpless 2017).

Evasion of oncogene-induced senescence, at least in cell culture, can occur due to loss-of-function (LOF) mutation in the CDKN2A gene product p16INK4A that acts as a cyclin-dependent kinase inhibitor (reviewed in Sharpless and Sherr 2015). LOF mutations in the CDKN2A gene that affect its other protein product, p14ARF, involved in stabilization of TP53 protein (p53), can contribute to evasion of oncogene-induced senescence (reviewed in Fontana et al. 2019).

LOF mutations in p16INK4A and p14ARF also contribute to evasion of oxidative stress-induced senescence (reviewed in Sharpless and Sherr 2015, and Fontana et al. 2019, respectively).