Aging-associated DNA methylation changes in middle-aged individuals: The Young Finns Study

Background Chronological aging-associated changes in the human DNA methylome are studied by multiple epigenome-wide association studies (EWAS); however, the aging-associated DNAmet changes identified among different age groups and tissues vary and especially the rates of aging-associated alterations in the epigenome during adulthood remain unclear. Here, we further explore and characterize CpG-sites where DNA methylation levels alter at a constant rate during adulthood and are also independent of blood cell type heterogeneity. Results In the study, we observed 1,202 aging-associated CpG-sites (a-CpGs), of which 48% were hypermethylated with advancing age in whole blood with an especially narrow age range (40 - 49 years). Repeatedly reported a-CpGs in ELOVL2, FHL2, PENK and KLF14 were also identified. Regions with aging-associated hypermethylation were enriched to several gene ontology terms (especially on the cluster of developmental processes), while hypomethylated sites showed no enrichment. The genes with a higher number of a-CpG hits were more often hypermethylated. Of the 1,202 aging-associated CpG-sites in the present study, 987 were identified in previous study (Vitality 90+) as differentially methylated also between nonagenarians and young adults in a previous study, and importantly, the directions of changes were identical in the previous and in the present study. Conclusions The set of 987 replicated a-CpGs presented here are altered in strong association with chronological aging in the whole range of adulthood. Consequently, future studies should note the variability of the types of a-CpGs, and the a-CpGs presented here should be dissociated from the environmental-sensitive CpG-sites or from regions that are associated with aging in a non-linear manner due to the accumulation of senescence-related features. This report offers detailed and verified pool of a-CpGs in which DNAmet levels associate linearly with chronological age and of which are different from the non-linearly changing ones. Bisulphite converted DNA from 184 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip