A meta-analysis on age-associated changes in blood DNA methylation: results from an original analysis pipeline for Infinium 450k data

Abstract

Aging is characterized by a profound remodeling of the epigenetic architecture in terms of DNA methylation patterns. To date the most effective tool to study genome wide DNA methylation changes is Infinium HumanMethylation450 BeadChip (Infinium 450k). Despite the wealth of tools for Infinium 450k analysis, the identification of the most biologically relevant DNA methylation changes is still challenging. Here we propose an analytical pipeline to select differentially methylated regions (DMRs), tailored on microarray architecture, which is highly effective in highlighting biologically relevant results. The pipeline groups microarray probes on the basis of their localization respect to CpG islands and genic sequences and, depending on probes density, identifies DMRs through a single-probe or a region-centric approach that considers the concomitant variation of multiple adjacent CpG probes. We successfully applied this analytical pipeline on 3 independent Infinium 450k datasets that investigated age-associated changes in blood DNA methylation. We provide a consensus list of genes that systematically vary in DNA methylation levels from 0 to 100 years and that have a potentially relevant role in the aging process.

Human Lung Tissue Transcriptome: Influence of Sex and Age

“…Indeed, sex differences in DNA methylation, leading to differential gene expression at various loci, have been reported [34]. Moreover, age-related changes in DNA methylation have also been observed [35]. …”

Improved age determination of blood and teeth samples using a selected set of DNA methylation markers

“…More recently, ELOVL2 was again highlighted as the top gene of high-confidence aging-associated CpG sites in blood when comparing nonagenarians with young healthy controls, 15 and both ELOVL2 and EDARADD were included in a shortlist of 44 regions most significantly associated with age in a meta-analysis. 16 Differentiating themselves from other researchers, Florath and her team employed a longitudinal study design to examine the relationship between DNA methylation and aging by collecting blood samples from 67 individuals at baseline and 8 years later. 3 Analysis of 94 CpG sites that were initially shown to be significantly correlated with age in a previous confirmatory analysis in an independent sample of 498 participants, revealed a significant change in methylation level within these 8 years of life for 78 of these CpG sites.…”

“…In addition, a meta-analysis on the association between DNA methylation and age in blood resulted in 44 genes whose methylation levels were highly correlated with age. 16 Among these genes were ELOVL2 and EDARADD. Recently, 2 other papers were published: GRIA2 and NPTX2 were suggested as potential markers for age prediction in blood and saliva samples, though accuracy was fairly low with an average difference of 6.9 and 9.2 years, respectively.…”

Long-term ambient particle exposures and blood DNA methylation age: findings from the VA normative aging study

“…DNA methylation is an epigenetic mark involved in regulating genomic structure and transcription [13]. Reproducible changes in DNA methylation have long been associated with chronological aging [14–16] and recent studies report persisting associations even after accounting for age-related cellular heterogeneity, a previously neglected confounder [17–19]. DNA methylation age (DNAm-age) is a novel tissue-independent predictor of chronological age and is calculated by an algorithm that uses methylation values from 353 chronological age-correlated CpG dinucleotides in Illumina’s HumanMethylation450 BeadChip [20, 21].…”