The Complex Bidirectional Relationship Between Aging and Atherosclerosis: Mechanistic Insights and Translational Opportunities.

Abstract

Aging is a major independent risk factor for atherosclerosis (AS), which in turn can accelerate systemic aging, thereby creating a self-reinforcing pathological cycle. These two processes share fundamental molecular mechanisms, such as endothelial dysfunction, phenotypic switching of vascular smooth muscle cells (VSMCs), immune senescence, mitochondrial oxidative stress, and the senescence-associated secretory phenotype (SASP). These overlapping pathways promote chronic inflammation and vascular injury, thereby advancing AS progression and contributing to systemic physiological decline. This review examines the shared mechanisms underlying aging and AS and evaluates emerging therapeutic strategies aimed at disrupting this bidirectional relationship, including senolytics, anti-inflammatory agents, and NAD⁺ supplementation. Targeting these converging pathways presents a promising strategy for mitigating cardiovascular disease and extending the health span.