Neurodegenerative diseases tend to occur later in life, and studies of central nervous system (CNS) aging could deepen our understanding of those diseases. In this study, we profiled the transcriptomes of 71,144 spinal cord cells from both of young and old mice, and identified 1, 215 aging-associated differentially expressed genes, including up regulation of C4b and Gfap. Interestingly, we observed significant expansion of DAM (Disease-Associated Microglia)/ATM (Axon Tract-Associated Microglia)-like Gpnmb+ microglia in old spinal cord, which were enriched with DAM/ATM marker genes of Gpnmb, Spp1, Lpl, Igf1, Itgax, Lgals3, Apoe and displayed highest enrichment with senescent genes. Furthermore, we also discovered 619 age-associated Ligand-Receptor Interaction changes and revealed 1277 age-related DEGs in 30 neuronal subpopulations. Overall, our study provided the first single-cell transcriptomic study of mouse spinal cord aging, and our finding of age-related expansion of Gpnmb+ microglia could have potential implications for the treatment of associated CNS diseases.