Fig. 3: Sex-specific miRNA dynamics in brain aging across male and female.

Sex-specific analysis, with male samples shown on the left and female on the right. a Time series boxplots of mmu-miR-9-5p in three brain regions. Spearman’s rank correlation coefficient of miRNA expression with age is displayed above each plot (significant, if adjusted p-value < 0.05, two-sided Spearman’s rank correlation test, Benjamini-Hochberg procedure). Boxplots follow Fig. 1c and Methods; exact values in Supplementary Data 4 and 5. b Barplots of significantly anti- or positively correlated miRNAs with age per brain region (|R| \(\ge\) 0.5, Spearman’s rank correlation coefficient, adjusted p-value < 0.05, two-sided Spearman’s rank correlation test, Benjamini-Hochberg). Upper bars contain miRNAs in the same direction significantly correlated in multiple brain regions (yellow). Lower bars contain miRNAs unique for one region (colors refer to brain regions (Fig. 1a)). c Features significantly correlated in multiple brain regions. Dots indicate brain regions, background color yellow (green), if significantly positively correlated (anti-correlated). d Heatmaps showing up- or downregulated miRNAs per brain region between older ages and 3 months (fold change \(\ge\) 1.5 or \(\le\) 1/1.5). Numbers are shown if more than 200 miRNAs. e Significantly upregulated miRNAs (yellow; fold change \(\ge\) 1.5, adjusted p-value < 0.05) and significantly downregulated (green; fold change \(\le\) 1/1.5) in multiple brain regions. Colors analog to Fig. 3c. f Summary of brain region-specific and age-related features. Purple markers indicate brain region-specific features from Fig. 2a. Arrows pointing to the top in yellow (bottom in green) stand for significantly upregulated (downregulated) miRNAs and positive in yellow (negative in green) signs for significantly positively (anti-) correlated miRNAs. g Human ROSMAP²⁹ data: Healthy samples split by age of death (71-80, 81-91, 92-102 years). Color indicates the log2-fold changes between the youngest and oldest group per sex. Black borders mark if the fold change exceeds |log2(1.5)|. Asterisks indicate significance (two-sided Welch’s t-test, Benjamini-Hochberg). h Scatterplot of Cohen’s \(d\) against log2-fold change, colored if thresholds for fold change (|log2(fc)| \(\ge\) log2(1.5)) and effect size (|d| \(\ge\) 0.5) are exceeded (upregulation yellow and downregulation green). Labeled miRNAs were age-correlated in mot. cortex (Supplementary Fig. 4c).