Cells accumulate DNA damage over time and enter senescence — a permanent growth arrest. Senescent cells (orange) secrete the SASP (Senescence-Associated Secretory Phenotype), promoting inflammation and paracrine senescence in neighbors.
Hayflick (1961): cells stop dividing after ~50 divisions (telomere shortening). p53/p21 and p16/Rb pathways enforce arrest. Clearance of senescent cells by senolytics extends healthspan in mice (Baker et al. 2011).