Fig. 4: Epigenome and transcriptome changes over human adult lifespan.

a Heatmap of ATAC-seq data (fitted values from ARIMA models) with a significant chronological trend in women (left, n = 13,297) and men (right, n = 13,295), as a function of age in years. Values represent z-score normalized accessibility values relative to the row (i.e., peak) mean. K-means clustering was used to group these peaks into three clusters in men and women (M1/F1, M2/F2, M3/F3). Color bar on the top represents discrete age groupings as defined in this study (young, middle-aged, older). Rows are annotated according to their position relative to the nearest TSS: proximal if <1 kbp distance, distal otherwise. b ChromHMM state annotations of temporal peak clusters in women (F1–F3) and men (M1–M3). Colors represent hypergeometric enrichment test p-values; light gray cells indicate insufficient number of genes to run an enrichment test. c Heatmap of ARIMA-fitted expression values for genes with a significant chronological trend in women (left, n = 1068) and men (right, n = 1471), as a function of age in years. Three clusters per sex are identified using k-means clustering: F1–3 and M1–3. Values represent z-score normalized expression values relative to the row (i.e., gene) mean. d Annotation of temporal gene clusters using cell-specific gene sets derived from single-cell RNA-seq data. Colors represent hypergeometric enrichment test p-values; light gray cells in plot indicate that there were insufficient genes in the gene sets to run an enrichment test. e Inverse log p-value distributions from breakpoint analysis for each cluster for women (top) and men (bottom), where curve height indicates magnitude of differences between preceding and succeeding age windows. Note that there are two age brackets where epigenomic changes take place abruptly both in men and women. Points and vertical lines mark median age estimates for a breakpoint integrated over multiple scales, and C1–C3 correspond to temporal clusters M1–M3 or F1–F3 from each sex (see the “Methods” section and Fig. S5c for details). Source data are provided as a Source Data file for (a–e).