Fig. 3: Common downregulation of genes across cell types.

a, Number of downregulated (blue) and upregulated (red) genes for each cell type in elderly donors. DEGs, differentially expressed genes. b, Heat map of significantly downregulated differentially expressed genes in elderly donors. Genes not differentially expressed are in white. The leftmost genes are defined as common across cell types (down in one or more excitatory, one or more inhibitory and two or more non-neuronal cell types). c, GO terms of genes downregulated in ageing plotted as general categories (see Supplementary Table 8 for full GO results). Housekeeping functions (shades of blue) are commonly downregulated. d, Housekeeping genes are significantly downregulated in elderly relative to adult brains in all neuron types. Boxes show median, first and third quartiles. Whiskers show 1.5 × IQR beyond the first and third quartiles (****P < 0.0001 and fold change < −0.05, two-sided Wilcoxon rank-sum test; elderly n = 7, adult n = 9). e, Mean gene effect score for all of the downregulated (blue) and upregulated (red) genes (in elderly versus adult donors) in the DepMap database. The downregulated genes for both neurons (left) and microglia (right) are more essential than the upregulated genes (two-sided t-test; neurons down n = 1,954, neurons up n = 455, microglia down n = 149, microglia up n = 75; neurons ****P = 7.33 × 10⁻⁷, microglia ****P = 9.09 × 10⁻⁷). Boxes and whiskers as in d. Points beyond whiskers are outliers. f,g, Fold change in elderly versus adult ribosomal-protein genes from both the small and the large subunit by snRNA-seq (two-sided t-test; elderly n = 7, adult n = 9) (f) and MERFISH (two-sided Wilcoxon rank-sum test; elderly n = 3, adult n = 3) (g). Inb, inhibitory. Genes shown in both f and g are colour-coded. Boxes and whiskers as in e. h, Expression of immediate early genes in excitatory neurons decreases with age. Grey shading, 95% confidence intervals. All data points shown (*P < 0.05, **P < 0.01, ***P < 0.001).