Fig. 2: Cellular senescence: from regulation to involvement in aging.

a Multiple stress signals arising from inducers (yellow) are sensed by regulators (blue) that include damage-related and epigenetic-related regulators. Signalling platforms may also act as main regulators. These interconnected regulators integrate, modulate and transmit senescent signals to the downstream effectors that include p53, p21, p16, Rb, E2F, NF-κB, C/EBPβ, mTOR, Notch and NLRP3 (red). These effectors ultimately trigger the main outcomes of cellular senescence (cell cycle arrest and SASP) (grey). SASP Senescence-associated secretory phenotype. b Over time, senescent cells accumulate in tissues due to increased cumulative damage exposure and reduced clearance (through decreased immune system activity). This accumulation leads to stem cell exhaustion, aberrant cellular responses, paracrine senescence (amplifying senescent cells accumulation) and modification of surrounding microenvironment. These cellular alterations lead to tissue dyshomeostasis, fibrosis, systemic inflammation and immunosenescence, finally contributing to aging and age-related pathologies.