Panvascular aging as a unifying framework: convergent mechanisms across age-related diseases

Panvascular aging is characterized by a systemic decline in vascular integrity that underlies the pathogenesis of multiple age-related diseases. Rather than affecting isolated vascular beds, aging triggers widespread changes across the entire circulatory system, including both large vessels and microcirculation in multiple organs. Core mechanisms encompass endothelial dysfunction, glycocalyx degradation, oxidative stress, inflammaging(definition), and disturbed mechanotransduction, which converge to impair vascular homeostasis. At the cellular level, telomere(definition) shortening, epigenetic remodeling, and vascular smooth muscle cell phenotypic switching accelerate senescence(definition) and extracellular matrix stiffening. Importantly, panvascular aging propagates through systemic inter-organ axes, such as the brain-vascular and heart-kidney networks, thereby amplifying shared pathogenic pathways and promoting organ dysfunction. Consequently, it constitutes an integrative framework linking cardiovascular disease, diabetes, chronic kidney disease, and neurodegeneration. Recognizing panvascular aging as a common pathophysiological axis underscores the importance of developing systemic strategies that enhance vascular resilience beyond singular disease-oriented approaches. Emerging therapeutic strategies - including senotherapeutics, epigenetic modulators, glycocalyx restoration, and metabolic restoration - are being explored as promising interventions to attenuate vascular aging and mitigate multimorbidity. This review synthesizes current insights into the molecular and mechanobiological mechanisms of panvascular aging and frames it as a conceptual keystone in aging biology, highlighting translational opportunities for the prevention and treatment of chronic age-related diseases.