Figure 2.

Routes towards clearance or persistence of senescence in vivo. Senescent cells can be generated in response to multiple physiological and pathological stimuli. The canonical pathway involves the onset of acute senescence—a state associated with leukocyte recruitment and clearance of senescence—as seen in development and wound healing in vivo. With advancing age and in response to other stimuli there is often incomplete clearance of senescent cells, which undergo further phenotypic alterations, upregulate SASP release, nuclear remodeling, and alter the expression of multiple genes including Lamin B1 and β-gal. These chronically senescent cells appear resistant to apoptosis and phagocytosis, and are believed to mediate organ dysfunction and fibrosis via their secretory phenotype. Whether these altered outcomes reflect altered initial stimuli, the cell type, the age of the subject, or other unknown factors remain incompletely understood.