Pro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell (VSMC) senescence. Senescence of VSMCs contributes to cardiovascular diseases by promoting arterial remodeling and stiffness. Ferroptosis, a form of regulated cell death, is linked to lipid oxidation and is distinct from apoptosis and necrosis. This study shows that pro-ferroptotic signaling in VSMCs accelerates vascular NAD⁺ loss, remodeling, and aging. Pro-ferroptotic signaling is activated in senescent VSMCs and aged mice. Inhibition of pro-ferroptotic signaling reduces VSMC senescence, vascular stiffness, and abdominal aortic aneurysm progression. Mechanistically, inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of PPARγ, impairing NCOA4-centered ferritinophagy. Pro-ferroptotic signaling correlates with arterial stiffness in a human study. These findings suggest that targeting pro-ferroptotic signaling could be a therapeutic strategy for vascular aging-related cardiovascular diseases. VSMC-specific overexpression of GPX4, but not its inactive mutant, ameliorates vascular senescence and aging. Genetic inhibition of pro-ferroptotic signaling reduces vascular NAD⁺ loss, senescence, and stiffness. Pro-ferroptotic signaling drives vascular senescence via secretome-dependent and independent mechanisms. Inhibition of pro-ferroptotic signaling suppresses ferritinophagy by regulating PPARγ signaling. PPARγ interacts with NCOA4, leading to the dissociation of the NCOA4-ferritin ferritinophagic complex. Pro-ferroptotic signaling is associated with arterial aging and stiffness in humans. These findings highlight the role of pro-ferroptotic signaling in vascular aging and suggest potential therapeutic targets for cardiovascular diseases.Pro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell (VSMC) senescence. Senescence of VSMCs contributes to cardiovascular diseases by promoting arterial remodeling and stiffness. Ferroptosis, a form of regulated cell death, is linked to lipid oxidation and is distinct from apoptosis and necrosis. This study shows that pro-ferroptotic signaling in VSMCs accelerates vascular NAD⁺ loss, remodeling, and aging. Pro-ferroptotic signaling is activated in senescent VSMCs and aged mice. Inhibition of pro-ferroptotic signaling reduces VSMC senescence, vascular stiffness, and abdominal aortic aneurysm progression. Mechanistically, inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of PPARγ, impairing NCOA4-centered ferritinophagy. Pro-ferroptotic signaling correlates with arterial stiffness in a human study. These findings suggest that targeting pro-ferroptotic signaling could be a therapeutic strategy for vascular aging-related cardiovascular diseases. VSMC-specific overexpression of GPX4, but not its inactive mutant, ameliorates vascular senescence and aging. Genetic inhibition of pro-ferroptotic signaling reduces vascular NAD⁺ loss, senescence, and stiffness. Pro-ferroptotic signaling drives vascular senescence via secretome-dependent and independent mechanisms. Inhibition of pro-ferroptotic signaling suppresses ferritinophagy by regulating PPARγ signaling. PPARγ interacts with NCOA4, leading to the dissociation of the NCOA4-ferritin ferritinophagic complex. Pro-ferroptotic signaling is associated with arterial aging and stiffness in humans. These findings highlight the role of pro-ferroptotic signaling in vascular aging and suggest potential therapeutic targets for cardiovascular diseases.