The mammalian brain can be divided into distinct structural and functional regions to perform a variety of diverse functions, but during normal aging, exactly how each region is affected, and the information interaction changes between different regions, remains largely unknown. To gain a better insight into these processes, here we generate a single-cell spatial transcriptomic (ST) atlas of young and old mice brains involving cerebrum, brain stem and fiber tracts regions. Based on the unbiased classification of spatial molecular atlas, 27 distinguished brain spatial domains were obtained, which are similar to known anatomical regions, but slightly different. Through differential expression analysis and gene set enrichment analysis (GSEA), we identified aging-related genes and pathways that vary in a coordinated or opposite manner across regions. Combined with single-cell transcriptomic data, we characterized the spatial distribution of cell types, identified an up-regulated gene Ifi27 across regions and cell types in VIS region. Through ligand-receptor interaction analysis, we identified all possible information interaction changes between regions with aging. In summary, we establish a brain spatial molecular atlas (accessible online at https:) to provide a rich resource of spatially differentially expressed genes and information interaction, which may help to understand aging and provide novel insights into the molecular mechanism of brain aging. Overall design: 8 slices from young (2 months old) and old mice (28 months old) (strain C57BL/6J) were prepared according to Visium spatial protocols of tissue preparation guide (10x genomics). The brains were rapidly extracted from the cranial cavity, and immediately submerged in ice-cold artificial cerebrospinal fluid. The brains were then blotted to remove excess liquid. The brains were subsequently embedded in Optimal Cutting Temperature compound (OCT) and frozen in isopentane (2-methylbutane, Sigma) precooled with dry ice and liquid nitrogen. The brains were cut into 10-um sections.