From:  Endothelial dysfunction and vascular stiffness: molecular drivers of cardiovascular aging

 Major signaling pathways in vascular aging.

PathwayRole in endothelial dysfunctionRole in vascular stiffnessReferences
NF-κBInduces pro-inflammatory cytokinesPromotes ECM remodeling[18, 33, 37, 38]
JAK/STATCytokine-driven vascular inflammationVSMC activation, calcification[33, 34]
Nrf2Antioxidant defense, ↓ with agingFailure of redox balance[3133]
AMPKEnhances eNOS, energy sensorLoss reduces vascular resilience[34, 35]
mTORPromotes growth, senescenceECM deposition, calcification[34, 36]
Sirtuins (SIRT1)Suppresses NF-κB, ↑ NOProtects mitochondria, anti-fibrotic[34, 37, 38, 40]

NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; JAK/STAT: Janus kinase/signal transducer and activator of transcription; Nrf2: nuclear factor erythroid 2-related factor 2; AMPK: AMP-activated protein kinase; mTOR: mechanistic target of rapamycin; SIRT1: sirtuin 1; ECM: extracellular matrix.