Longevity & AgingFibulin-1 Drives Vascular Aging Through a ZNF384–TGF-β Senescence Loop
Researchers identified Fibulin-1 (Fbln1), an extracellular matrix protein, as a key driver of vascular stiffness in both aging and hypertensive mouse models. The transcription factor ZNF384 directly activates Fbln1 expression by binding its promoter. Elevated Fbln1 then activates TGF-β/Smad3 signaling, promoting vascular smooth muscle cell (VSMC) senescence and collagen accumulation. Knocking out Fbln1 reduced pulse wave velocity, reversed VSMC senescence markers, and lessened collagen deposition. Blocking TGF-β/Smad3 abolished these Fbln1-driven effects. Elevated plasma Fbln1 also correlated with hereditary vascular stiffness in human family pedigrees, suggesting its potential as both a biomarker and therapeutic target for age-related arterial disease.
