Cellular Senescence and Vascular Calcification: Mechanistic Crosstalk and Potential of Dual-Targeting Strategies

Vascular calcification (VC), a key predictor of cardiovascular morbidity and mortality, is an active cell-mediated pathological process deeply coupled with cellular senescence. This review systematically dissects the mechanisms by which senescent vascular smooth muscle cells, endothelial cells and macrophages drive VC progression via phenotypic switching, intercellular crosstalk, and endothelial–mesenchymal transition and clarifies the extensive signaling crosstalk and heterogeneous regulation between cellular senescence and VC. Nevertheless, these two biological processes do not inevitably occur in parallel, and experimental evidence indicates that they may diverge in some settings. We further summarize representative senotherapeutic agents that concurrently suppress cellular senescence and VC, including fisetin, dasatinib plus quercetin, metformin, sodium-glucose cotransporter 2 inhibitors, and liraglutide, and elaborate their core regulatory targets such as AMP-activated protein kinase, silent information regulator 1/6, nuclear factor kappa B and nuclear factor erythroid 2-related factor 2. Of note, direct experimental evidence demonstrating whether these pharmacological interventions attenuate VC via modulating SASP remains limited. Finally, we address key challenges in this field and provide novel perspectives for senescence-associated VC therapeutic strategies.