Fig. 3: Sex-dimorphic changes in monocyte- and B cell-associated loci.

Correlation of age-related ATAC-seq (a) and RNA-seq (b) remodeling between women and men PBMCs. Note the overall large and positive Pearson correlation coefficients. Genes are associated to ATAC-seq peaks based on nearest TSS, and are color coded in both plots according to their association to immune modules (purple: T cells, green: B cells, pink: NK cells, yellow: monocytes). Only regulatory (TSS/enhancer) peaks are included and peaks-genes are matched between both plots (n = 10,707 loci). Blue-red gradient on data points represents their relative local density. (c) Correlation between sexes for age-related ATAC-seq remodeling stratified by cell-specific loci from chromHMM annotations. Note that the highest correlation is observed in naive T cells (n = 833 peaks), which is associated with negative fold changes (i.e., loss in chromatin accessibility with age) in both sexes. Chromatin remodeling correlates the least between sexes for B cell- (n = 1645 peaks) and monocyte-specific loci (n = 6861 peaks), with NK cells (n = 3,008 peaks) showing a positive trend in both sexes. d Correlation between sexes for age-related RNA-seq remodeling stratified by cell-specific genes from single-cell RNA-seq data. Note that the highest correlation is observed in naive T cells (n = 70 genes), which is associated with negative fold changes (i.e., downregulation with age) in both sexes. On the other hand, NK cells (n = 403 genes) are highly correlated between sexes and associated with increased expression with age in both sexes. In agreement with ATAC-seq data, gene expression remodeling correlates the least between sexes for B cell- (n = 144) and monocyte-specific genes (n = 748). Values at the top left corner represent the Pearson correlation coefficient between sexes only for the genes/loci associated to that cell type. e Normalized expression and accessibility levels for important molecules associated to T, cytotoxic, and B cells. LogFC = mean log2 of fold changes between old and young samples; MA = middle-aged. Box plots represent median and IQR values, with whiskers extending to 1.5 times the IQR. Source data are provided as a Source Data file for (a–d).