Fig. 1.

Triggers, effector pathways and features of senescence in tissue dysfunction, ageing and chronic diseases. Inducers triggering senescence vary depending on the context, including DNA damage, reactive oxygen species (ROS), oncogenic mutations, metabolic insults, proteotoxic stress and other unknown factors. Cellular senescence is activated via p53/p21, p16/pRB dependent pathways. One typical feature of senescent cells, the senescent cell anti-apoptotic pathways (SCAPs), predisposes senescent cells to be apoptosis-resistant, resulting in their accumulation in tissues. The SCAPs are thus key targets of senolytic drugs for targeting and inducing senescent cells to undergo apoptosis. Another feature of senescent cells is the senescence-associated secretory phenotype (SASP), characterized by a secretion profile of pro-inflammatory cytokines, growth factors and soluble receptors, which could further result in both local and systemic inflammation and tissue damage effect. Activation of interleukin-1 (IL-1), tumor growth factor β (TGF-β), nuclear factor (NF)-кB (NF-кB), p38 mitogen-activated protein kinases (p38 MAPK) and inflammasome signaling are factors promoting generation of SASP.