Evaluation of short-term epigenetic age fluctuation

Abstract

Considerable effort has been spent on lowering and maintaining the epigenetic age. However, the extent to which epigenetic age fluctuates under normal conditions is poorly understood. Therefore, we analyzed methylation data from monocytes and peripheral blood mononuclear cells collected from two Japanese men. The ranges of the Pan-tissue, Skin and blood, and DNAm PhenoAge epigenetic age during 3 months were ≥ 5.62, ≥ 3.04, and ≥ 8.23 years, and the maximum daily changes were 5.21, 3.20, and 6.53 years, respectively. These fluctuations were not suppressed by correcting for cell-type composition. Although the underlying biological mechanism remains unclear, there was a nonnegligible degree of age fluctuation which should inform personalized clinical applications.

Keywords: Blood DNA methylation; Epigenetic clock; Healthy individuals; Normal condition.

Fig. 1

Epigenetic age fluctuation and underlying characteristics based on Horvath-normalized datasets. a Longitudinal change of epigenetic ages in peripheral blood mononuclear cells (PBMCs) and monocytes in the two individuals (Person A and Person B). The ages were calculated based on three clocks. b Relationships between longitudinal DNA methylation change (standard deviation: SD) and the coefficient assigned to the clock CpGs. The dashed line indicates coefficient = 0. The single DNAm PhenoAge clock CpG exhibited a greater SD in the PBMCs of Person A (> 0.15), as is indicated by an arrow. c Proportions of CpG and genic annotations of all clock CpGs (all), CpGs with a higher contribution to epigenetic age fluctuation (top 25% CpGs; high), and CpGs with a lower contribution (bottom 25% CpGs; low). Asterisks indicate a significant difference in annotation proportion. d Contribution of CpGs with type I and II probes to epigenetic age fluctuation (SD × coefficient)