Cellular senescence has emerged as a unifying biological mechanism linking ageing to the progressive dysfunction of the heart, vasculature, kidneys, and metabolic tissues. In the cardio-diabetes-renal (CDR) continuum, persistent accumulation of senescent cells—driven by metabolic stress, oxidative injury, and chronic inflammation—promotes fibrosis, vascular stiffness, insulin resistance, and organ failure through the senescence-associated secretory phenotype (SASP).

This comprehensive review examines the molecular biology of cellular senescence, its heterogeneity across tissues, and its central role in cardiometabolic and renal disease progression. It integrates experimental and clinical evidence linking senescence to obesity, type 2 diabetes, atherosclerosis, heart failure with preserved ejection fraction, and diabetic kidney disease.

The article further explores emerging therapeutic strategies, including senolytics and senomorphics, highlighting mechanisms of action, early human trial data, biomarker development, safety considerations, and ethical challenges. Emphasis is placed on clinical translation, trial design, and integration of senescence-targeted therapies into existing cardio-diabetes-renal care pathways.

By reframing chronic cardiometabolic diseases as manifestations of accelerated biological ageing, this work positions senescence-informed medicine as a transformative paradigm—shifting clinical focus from isolated organ dysfunction toward preservation of functional reserve, resilience, and health span.