Fig. 4: Age-associated changes in region-specific gene expression programs.

a, Bar charts depict the number of genes DE between adult and aged animals across various brain regions, categorized as upregulated (red) and downregulated (blue). DE genes are defined by more than threefold changes between the ages with an FDR-adjusted P value < 0.05. Numbers of significant genes were calculated from region-specific DE analysis for aging using the likelihood-ratio test in Monocle2; q-values denote multiple-testing-adjusted P values. Significant genes were defined as those with q < 0.05, FC > 3 between the highest and second-highest expressed conditions and TPM > 50 in the highest expressed condition. b, Heatmap showing the log2-transformed FCs in normalized gene expression between aged and adult animals for DE genes across different brain regions, distinguishing shared changes (left) from region-specific changes (right). c, Barplots showing the scaled expression and standard error of gene modules related to interferon response across brain regions in both adult (blue) and aged (red) conditions. Gene inclusion for interferon module (Ifi27, Ifitm3, Ifi27l2a, Isg20, Isg15, Ifit3, Rtp4) (b). Expression values for each pathway were calculated by aggregating and normalizing pathway-related gene expressions, followed by log transformation and scaling. d, Reconstructed spatial maps display the expression levels of gene modules associated with the complement and interferon response pathways in adults (top) and aged animals (bottom) for sections 2 (left) and 3 (right).