Fig. 2.

Schematic representation of how secondary senescence is established from primary senescence. There are two forms of primary senescence: oncogene-induced senescence (OIS) and Notch-induced senescence (NIS). These primary senescent cells can further trigger secondary senescence in their neighbouring cells in the process called secondary senescence, which can be mediated by cell-to-cell contact and/or paracrine transmission of senescence-associated secretory phenotype (SASP). Notch-dominant secondary senescence relies on expression of growth factors and TGFβ as well as the induction of fibrillar collagens. SASP-dominant secondary senescence, on the other hand, is driven by release of proinflammatory cytokines, expression of C/EBPβ and spread of SASP. Both Notch-driven and SASP-driven secretome profiles are found to contribute to a population of secondary senescent cells. Under normal conditions, the combined consequences of paracrine and juxtacrine signalling include the recruitment of immune cells and clearance of senescent cells. Here, primary and secondary senescent cells are viewed as functionally distinct endpoints