Aging is a major risk factor for cerebrovascular disease. However, the molecular mechanisms of cerebrovascular aging remain to be clarified. In this study, we performed proteomics analysis aimed to reveal the molecular signaling pathways during aging.our study demonstrated that the imbalance of vasodilators and vasoconstrictors caused by downregulation of NOS3, oxidative stress mediated by the suppression of NRF2 pathway, and miRNA-regulated accumulation of ECM proteins were critical for cerebrovascular aging.