Progranulin deficiency in mice triggers premature vascular senescence, causing endothelial dysfunction, enhanced vasoconstriction, and vascular inflammation even in young 6-month-old animals. Transcriptomic analysis revealed that progranulin-deficient vascular smooth muscle cells exhibited classic senescence signatures including impaired mitochondrial oxidative phosphorylation, epigenetic dysregulation, and excessive collagen pathway activation. Notably, progranulin expression naturally increases with age in both human and mouse arteries, correlating strongly with p21 senescence marker levels. This discovery illuminates a previously unknown protective mechanism against vascular aging. Progranulin appears to function as a cellular guardian, maintaining vascular homeostasis through coordinated regulation of mitochondrial function, inflammation, and structural integrity. The finding carries significant implications for cardiovascular disease prevention, as progranulin deficiency may predispose individuals to early-onset vascular dysfunction and kidney damage. While senolytic drugs partially improved endothelial function in deficient mice, they also increased vascular contractility, suggesting complex therapeutic considerations. This mechanistic insight into how specific protein deficiencies accelerate vascular aging could inform biomarker development and therapeutic strategies targeting age-related cardiovascular disease, though human clinical validation remains essential.