BackgroundChanges in DNA methylation are among the mechanisms contributing to the ageing process. We sought to identify ageing-associated DNA methylation changes at single-CpG-site resolution in blood leukocytes and to ensure that the observed changes were not due to differences in the proportions of leukocytes. The association between DNA methylation changes and gene expression levels was also investigated in the same individuals.ResultsWe identified 8540 high-confidence ageing-associated CpG sites, 46% of which were hypermethylated in nonagenarians. The hypermethylation-associated genes belonged to a common category: they were predicted to be regulated by a common group of transcription factors and were enriched in a related set of GO terms and canonical pathways. Conversely, for the hypomethylation-associated genes only a limited set of GO terms and canonical pathways were identified. Among the 8540 CpG sites associated with ageing, methylation level of 377 sites was also associated with gene expression levels. These genes were enriched in GO terms and canonical pathways associated with immune system functions, particularly phagocytosis.ConclusionsWe find that certain ageing-associated immune-system impairments may be mediated via changes in DNA methylation. The results also imply that ageing-associated hypo- and hypermethylation are distinct processes: hypermethylation could be caused by programmed changes, whereas hypomethylation could be the result of environmental and stochastic processes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1381-z) contains supplementary material, which is available to authorized users.

BackgroundHuman aging is associated with profound changes in one of the major epigenetic mechanisms, DNA methylation. Some of these changes occur in a clock-like fashion, i.e., correlating with the calendar age of an individual, thus providing a new aging biomarker. Some reports have identified factors associated with the acceleration of the epigenetic age. However, it is also important to analyze the temporal changes in the epigenetic age, i.e., the duration of the observed acceleration, and the effects of the possible therapeutic and lifestyle modifications.MethodsTo address this issue, we determined the epigenetic age for a cohort of 183 healthy individuals using blood samples derived from two time points that were 25 years apart (between 15–24 and 40–49 years of age). Additionally, we also determined the epigenetic ages of 119 individuals in a cohort consisting of 90-year-old participants (nonagenarians). These were determined by using the Horvath algorithm based on the methylation level of 353 CpG sites. The data are indicated as the deviation of the epigenetic age from the calendar age (calendar age minus epigenetic age = delta age, ΔAGE). As obesity is often associated with accelerating aging and degenerative phenotypes, the correlation of the body mass index (BMI) with the ΔAGE was analyzed in the following three age groups: young adults, middle-aged, and nonagenarian.ResultsThe data showed that BMI is associated with decreased ΔAGE, i.e., increased epigenetic age, in middle-aged individuals. This effect is also seen during the 25-year period from early adulthood to middle age, in which an increase in the BMI is significantly associated with a decrease in the ΔAGE. We also analyzed the association between BMI and epigenetic age in young and elderly individuals, but these associations were not significant.ConclusionTaken together, the main finding on this report suggests that association between increased BMI and accelerated epigenetic aging in the blood cells of middle-aged individuals can be observed, and this effect is also detectable if the BMI has increased in adulthood. The fact that the association between BMI and epigenetic age can only be observed in the middle-aged group does not exclude the possibility that this association could be present throughout the human lifespan; it might just be masked by confounding factors in young adults and nonagenarian individuals.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0301-7) contains supplementary material, which is available to authorized users.

Background Non-coding RNA 886 (nc886) is coded from a maternally inherited metastable epiallele. We set out to investigate the determinants and dynamics of the methylation pattern at the nc886 epiallele and how this methylation status associates with nc886 RNA expression. Furthermore, we investigated the associations between the nc886 methylation status or the levels of nc886 RNAs and metabolic traits in the YFS and KORA cohorts. The association between nc886 epiallele methylation and RNA expression was also validated in induced pluripotent stem cell (iPSC) lines. Results We confirm that the methylation status of the nc886 epiallele is mostly binomial, with individuals displaying either a non- or hemi-methylated status, but we also describe intermediately and close to fully methylated individuals. We show that an individual’s methylation status is associated with the mother’s age and socioeconomic status, but not with the individual’s own genetics. Once established, the methylation status of the nc886 epiallele remains stable for at least 25 years. This methylation status is strongly associated with the levels of nc886 non-coding RNAs in serum, blood, and iPSC lines. In addition, nc886 methylation status associates with glucose and insulin levels during adolescence but not with the indicators of glucose metabolism or the incidence of type 2 diabetes in adulthood. However, the nc886-3p RNA levels also associate with glucose metabolism in adulthood. Conclusions These results indicate that nc886 metastable epiallele methylation is tuned by the periconceptional conditions and it associates with glucose metabolism through the expression of the ncRNAs coded in the epiallele region.