Fig. 5
From: Long-term cardiovascular complications following sepsis: is senescence the missing link?
Main pathways leading to cellular senescence. Mechanisms that drive cellular senescence include the direct activation of the DNA damage response (DDR) through the ATM/ATR pathway and/or of the INK4a/ARF locus through the assembly of PcG protein complexes eventually via the ANRIL scaffolding Lnc RNA. The INK4 family, among which p16, are cyclin-dependent kinase inhibitors targeting CDK4/6. Ultimately, p53/p21 and p16/Rb pathways are key players driving senescence. ANRIL: antisense non-coding RNA in the INK4 locus, ARF ADP ribosylation factor, ARHGAP18 (Rho GTPase activating protein 18), ATM ataxia-telangiectasia mutated, ATR ataxia-telangiectasia mutated and Rad3 related, CDKs cyclin-dependent kinases, Chk1 checkpoint kinase 1, Chk2 checkpoint kinase 2, DDR DNA damage response, INK4 inhibitors of CDK4, p16/Rb p16/retinoblastoma protein, PcG polycomb, Lnc RNA long non-coding RNA, ROS reactive oxygen species