Cellular Senescence as a Core Mechanistic Link between CKD, Cardiac Fibrosis, and Aging

CKD and cardiovascular disease frequently coexist and represent a major global health burden. Cellular senescence may connect these disorders through persistent inflammation, fibrosis, and metabolic stress. Senescent cells undergo sustained proliferative arrest and release a pro-inflammatory, pro-fibrotic secretome called the senescence-associated secretory phenotype. In kidney and heart tissue, persistent senescent cells may promote immune-cell infiltration, fibroblast activation, extracellular matrix deposition, and tissue stiffening. Human biopsy, cardiac-tissue, urinary-biomarker, circulating-proteomic, and early senolytic data support associations between senescence markers, kidney dysfunction, and cardiovascular remodelling. However, most causal and interventional evidence still comes from cell-culture and animal models. This review critically evaluates cellular senescence as a plausible cardiorenal-fibrosis mechanism while emphasizing that causality, biomarker specificity, and therapeutic benefit in humans remain to be fully elucidated.