Nonlinear DNA methylation trajectories in aging mice [RRBS]

Although DNA methylation data yields highly accurate age predictors, little is known about the dynamics of this quintessential epigenomic biomarker during lifespan. To narrow the gap, we investigated the methylation trajectories in DNA from 82 male mouse (C57BL/6J/Ukj) colons at five different time points (3, 9, 15, 24, 28 months). Our study indicates the existence of linear and nonlinear DNA methylation changes during aging. Precisely, we identify two epigenomic switches during early-to-midlife (3-9 mo) and mid-to-late-life (15-24 mo) transitions, separating the rodents' life into three major stages. The results were validated with samples from an independent mouse cohort of 20 male C57BL6/J mice at four different ages (3, 7, 12, 27 months). Reduced representation bisulfite sequencing (RRBS) of 82 genomic DNA samples from male mouse (C57BL/6J/Ukj) colon at different ages: 3 (n = 16), 9 (n = 16), 15 (n = 16), 24 (n = 16), and 28 (n = 18) months. In the validation experiment RRBS was performed on 20 genomic DNA samples from male mouse (C57BL6/J) colon at different ages: 3 (n = 4), 7 (n = 5), 12 (n = 5), and 27 (n = 6) months.