Animal experiments further confirmed increased SP1 and decreased SEPHS2 expression at both mRNA and protein levels in aged mouse brains, consistent with the bioinformatic findings.<h4>Conclusion</h4>This study identifies SP1 and SEPHS2 as key genes linking selenium to brain aging, providing new insights into the role of selenium in brain aging and suggesting that these genes may represent potential biomarkers or therapeutic targets for brain aging and aging-related brain disorders. This evidence concerns the gene SEPHS2 and brain disorder.