Vascular aging has been documented as a vital process leading to arterial dysfunction and age-related cardiovascular and cerebrovascular diseases. However, our understanding of the molecular underpinnings of age-related phenotypes in the vascular system is incomplete. Here we performed bulk RNA sequencing in young and old mouse aortae to elucidate age-associated changes in the transcriptome. Results showed that the majority of upregulated pathways in aged aortae relate to immune response, including inflammation activation, apoptotic clearance, and phagocytosis. The top downregulated pathway in aged aortae was extracellular matrix organization. Additionally, protein folding control and stress response pathways were downregulated in the aged vessels, with an array of downregulated genes encoding heat shock proteins (HSPs). We also found that circadian core clock genes were differentially expressed in young versus old aortae. Finally, transcriptome analysis combined with protein expression examination and smooth muscle cell (SMC) lineage tracing revealed that SMCs in aged aortae retained the differentiated phenotype, with an insignificant decrease in SMC marker gene expression. Our results therefore unveiled critical pathways regulated by arterial aging in mice, which will provide important insight into strategies to defy vascular aging and age-associated vascular diseases.