Decoding Vascular Senescence: Cellular Insights and Therapeutic Strategies

Figures

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  Figure 1. Structural and cellular remodeling of the vasculature during aging. Schematic comparison between young (left) and aged (right) blood vessels. Aging induces marked thickening of the vessel wall, accompanied by alterations in multiple cell types and ECM components. In the aged vasculature, ECs become senescent with impaired barrier function. VSMCs undergo phenotypic switching into proliferative, migratory, and foam-cell-like states, promoting calcification. Pericytes and fibroblasts also become senescent, while myofibroblasts accumulate. The ECM shows elastic fiber degeneration, excessive collagen deposition, and calcification. Inflammatory cells (including CD8+ T cells), cytokines, MMPs, and miRNAs are elevated, reflecting a pro-inflammatory SASP. Collectively, these integrated changes drive vascular stiffening, structural deterioration, and functional decay.

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  Figure 2. The twelve hallmarks of vascular aging and their crosstalk. Schematic illustrating the twelve hallmarks organized into three interconnected dimensions: (1) genomic and homeostatic instability (genomic instability, telomere attrition, epigenetic alterations, loss of protein homeostasis); (2) cellular and metabolic dysfunction (autophagy dysregulation, dysregulated nutrient sensing, mitochondrial dysfunction); and (3) cellular instability and microenvironmental evolution (cellular senescence, chronic inflammation, stem cell exhaustion, altered intercellular communication, impaired mechanosignaling). These multidimensional hallmarks collectively converge on the vascular wall, cooperatively driving the onset and progression of vascular aging.

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  Figure 3. Macro-phenotypes of vascular aging from EVA to SUPERNOVA. Schematic illustration of the determinants and stratification standards for EVA and SUPERNOVA. The left panel lists the risk factors and structural alterations driving EVA. The right panel outlines the protective mechanisms and lifestyle factors contributing to SUPERNOVA. The central panel defines the aging trajectories based on PWV and Δ-age calculation.

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  Figure 4. Vascular aging as a common pathological driver of systemic diseases. Schematic illustration of vascular aging and its associated systemic diseases. The inner rings depict age-related disorders across various organs, including AD, VCI, CVD, hypertension, CKD, diabetes, DR, alongside hereditary diseases. The outermost ring delineates the two primary shared pathophysiological dimensions—microvascular rarefaction and macrovascular hemodynamics—which serve as common pathways, driving specific organ pathologies through downstream microstructural alterations.