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Signalling mechanisms leading to senescence. Mechanical stress, DNA damage, ROS, oxidative stress and other adverse conditions induce cellular senescence. p53-p21-CDK2 and p16-CDK4/6 are two pathways involved in senescence. CDK2/4/6 inhibit RB and promote S phase entry, leading to cell cycle arrest and cellular senescence. ROS, reactive oxygen species; CDK, cyclin-dependent kinases; RB, retinoblastoma protein
