Background: The incidence of aging-related erectile dysfunction (ED) remains high in the elderly population, and has attracted the attention of the medical community. However, aging-related ED responds poorly to traditional treatments for ED, and its mechanism has not yet been fully clarified. This study sought to explore the potential mechanisms of aging-related ED based on bioinformatics and experimental verification.Methods: A bioinformatics analysis was performed on data from the Gene Expression Omnibus database related to ED and aging, and the associated differentially expressed genes (DEGs) and signaling pathways were identified. Young and aged rats (n=8 per group) were included in the experimental verification study. Erectile function was detected by electrical stimulation of the cavernous nerve. The corpus cavernosum was collected for the follow-up experiments.Results: A total of 4 hub genes were identified, among which biglycan (BGN) appears to play an important role. The functional enrichment analysis revealed that the extracellular matrix (ECM), especially collagen, related pathways, and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were enriched, which was also confirmed by the animal experiments. Impaired erectile function in aged rats was associated with the downregulation of the PI3K/AKT pathway, endothelial dysfunction, and increased fibrosis in the penis.Conclusions: Erectile function is impaired with aging. The downregulation of the PI3K/AKT pathway, endothelial dysfunction, and increased fibrosis are involved in this process. BGN may be the key gene regulating these changes. Our study extended understandings of the mechanisms of age-related ED and provides new potential treatment ideas.