Figure 1.

Stress-induced senescence. Both external and internal stresses can induce DNA damage and the activation of p16^INK4A and/or p15^INK4B. DNA damage can activate p53 ataxia telangiectasia mutated (ATM) and ATM and RAD3-related (ATR) pathway. Activated p53 induces p21 ^Cip1 expression. Expression of p21^Cip1 can also be regulated by p53-independent mechanisms. The Cyclin dependent kinases activate Rb but are inhibited by p15^INK4B/ p16^INK4A and p21^Cip1 which leads to cell cycle arrest and senescence. The senescent cells express senescence-associated secretory phenotype (SASP). The SASP factors may induce senescence in neighboring cells in a paracrine fashion. ATM: Ataxia telangiectasia mutated; SASP: Senescence-associated secretory phenotype.