Mouse Brain Aging

The goal of this study is to define the epigenetic and transcriptional changes that occur across brain regions and cell types during aging. We profiled chromatin accessibility using single-nucleus ATAC-seq in male C57BL/6 mice and paired chromatin accessibility and gene expression using 10x Multiome in female C57BL/6 mice, both across three ages: 2 months (young), 9 months (middle-aged), and 18 months (aged). In parallel, we performed MERFISH spatial transcriptomics on male brains at the same ages. Across eight brain regions, we generated single-cell profiles for over 1.5 million nuclei. This integrative approach enables detailed characterization of aging-associated changes in cell composition, transcription factor activity, and chromatin state. Our findings reveal widespread epigenomic reprogramming during brain aging and establish a foundational resource for investigating molecular drivers of age-related cognitive decline.