Fig. 2

The Ames dwarf epigenome appears more stable and buffered against age-associated hypomethylation. a The number of significantly differentially methylated CpGs (5% FDR, Fisher’s exact test) between 2 and 22-month-old WT (WT) and between 2- and 22-month-old Ames dwarf (Dwarf) mice. Hyper- and hypomethylated aCpGs are higher and lower in 22-month-old mice, respectively. b The number of significantly differentially methylated regions (aDMRs; 5% FDR, Fisher’s exact test, 500-bp windows) between 2- and 22-month-old mice for WT and Ames dwarf mice. Regions of heterogeneity (chi-squared test <0.05) across the four replicates in each cohort were removed. Significance (empirical p value) at p < 0.05 is indicated with an asterisk. See also Additional file 3. c The percentage methylation across all 2- (DY) versus 22-month-old (DO) Ames dwarf differentially methylated regions (aDMRs). Replicate samples (four mouse livers) are in rows and the aDMRs in columns. The intensity of the heatmap represents column scaled percentage methylation (Z-score), with values ranging from lower to higher methylation shown as blue to yellow. d The percentage methylation across all 2- (WTY) versus 22-month-old (WTO) WT differentially methylated regions (aDMRs). Replicate samples (four mouse livers) are in rows and the aDMRs in columns. Columns are scaled using Z-scores. The intensity of the heatmap represents Z-score, with values ranging from negative to positive shown as blue to yellow. e Kernel smoothed line plots of selected aDMRs, ±5 kb. WTY, 2-month-old dwarf (DY), WTO and 22-month-old dwarf (DO) replicates are represented by solid blue, solid red, dashed blue and dashed red lines, respectively. DMRs are highlighted in pink and CpGs in black. f The difference in mean percentage methylation per DMR (across all samples) between 22- and 2-month-old mice versus number of aDMRs. WT aDMRs are shown in red and dwarf aDMRs in blue. g Ratio of observed/expected (random) overlap between WT (from a–d) and UM-HET3 aDMRs. Hyper- and hypomethylated aDMRs are higher and lower in old mice, respectively. Significance (empirical p value) at p < 0.001 is indicated with double asterisks. h Mean percentage methylation per replicate across all hypermethylated aDMRs common to both WT and Ames dwarf mice (shared). WTY, WTO, DY and DO mice are shown in light blue, dark blue, light red and dark red, respectively. WTY versus WTO and DY versus DO at p < 0.001 are indicated with double asterisks (two tailed t-test on arcsine transformed proportions). i As h but showing shared hypomethylated aDMRs. WTY versus WTO, DY versus DO, WTO versus DO all p < 0.001 indicated with double asterisks and WTY versus DY p < 0.05 indicated with a single asterisk (two tailed t-test on arcsine transformed proportions). j Kernel smoothed line plots of selected aDMRs common to both WT and dwarf mice, ±5 kb. Pooled replicates for WTY, DY, WTO and DO are represented by solid blue, solid red, dashed blue and dashed red lines, respectively. DMRs are highlighted in pink and CpGs in black