Figure 5.

Schematic diagram of epithelial senescence in the lung. Cellular senescence can be triggered in response to different stimuli, including telomere shortening/damage and engagement of the DNA-damage response (DDR). Senescent cells upregulate expression of senescence-associated heterochromatin foci (SAHF), senescence-associated β-galactosidase activity (SA-β-gal), p16 and p21 and secrete a multitude of chemokines, cytokines, proteases, and growth factors known as the senescent-associated secretory phenotype (SASP). Senescent epithelial cells exert diverse roles in the lung due to the heterogeneity of SASP factors, including activation of fibroblasts and immune cells to drive fibrosis and inflammation, respectively. Senescent epithelial cells can also induce senescence in neighbouring cells, reinforcing growth arrest, impairing epithelial regeneration and efficient lung function. Senescent fibroblasts further impair lung function and repair of epithelial cells, suggesting bi-directionality and positive feedback mechanisms driving epithelial damage and fibroblast activation. Senolytic compounds including Dasatinib and Rapamycin can successfully attenuate fibroblast activation and immune cell recruitment in the lung, making modulation of senescence an attractive therapeutic target for several chronic diseases. Created using Biorender.com.