ArticleGenome biology2024
A comprehensive map of the aging blood methylome in humans.
Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Meta-analysis of DNA methylation aging signatures in 17 human tissues.Nature aging · 2026Pooled it
- The aging epigenome: integrative analyses reveal intersection with Alzheimer's disease.GeroScience · 2026Pooled it
- Integration of methylome and transcriptome reveals age-associated signatures of stage-specific dynamics and regulatory remodeling in dogs.GeroScience · 2026Article
- DNA Methylation as a Programmable Information Layer: From Molecular Marks to Disease State Engineering.International journal of molecular sciences · 2026Review
- Embracing non-linearity in human ageing.Nature reviews. Genetics · 2026Review
- From aging to Alzheimer's disease: concordant brain DNA methylation changes in late life.Genome medicine · 2026Article
- Cell-to-cell variability and gain of methylation at polycomb CpG islands as a hallmark of aging.Nature communications · 2026Article
- A unifying model of stem cell dynamics explains age-related methylation patterns across mammals.Nature aging · 2026Article
- Foundations of Gerophysics.Aging · 2026Article
- Exploring the exposome and unexplained variance in biological ageing - insights from a longitudinal twin study in adolescence and early adulthood.medRxiv : the preprint server for health sciences · 2026Article
- Sex-specific nonlinear DNA methylation aging trajectories reveal biomarkers of cancer risk and inflammation.Genome biology · 2026Article
- Early detection of multiple cancers: the era of methylation-based liquid biopsy.Frontiers in oncology · 2026Review
- Article
- TranslAGE: A Comprehensive Platform for Systematic Validation of Epigenetic Aging Biomarkers.bioRxiv : the preprint server for biology · 2025Article
- Epigenetic ageing clocks: statistical methods and emerging computational challenges.Nature reviews. Genetics · 2025Review
- Is the concept of mammalian epigenetic clocks universal and applicable to invertebrates?Frontiers in genetics · 2025Article
- A comprehensive map of the aging blood methylome in humans.Genome biology · 2024Article
- Genome-wide DNA methylation profiling of blood samples from patients with major depressive disorder: correlation with symptom heterogeneity.Journal of psychiatry & neuroscience : JPNArticle
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
backgroundDuring aging, the human methylome undergoes both differential and variable shifts, accompanied by increased entropy. The distinction between variably methylated positions (VMPs) and differentially methylated positions (DMPs), their contribution to epigenetic age, and the role of cell type heterogeneity remain unclear.
resultsWe conduct a comprehensive analysis of > 32,000 human blood methylomes from 56 datasets (age range = 6-101 years). We find a significant proportion of the blood methylome that is differentially methylated with age (48% DMPs; FDR < 0.005) and variably methylated with age (37% VMPs; FDR < 0.005), with considerable overlap between the two groups (59% of DMPs are VMPs). Bivalent and Polycomb regions become increasingly methylated and divergent between individuals, while quiescent regions lose methylation more uniformly. Both chronological and biological clocks, but not pace-of-aging clocks, show a strong enrichment for CpGs undergoing both mean and variance changes during aging. The accumulation of DMPs shifting towards a methylation fraction of 50% drives the increase in entropy, smoothening the epigenetic landscape. However, approximately a quarter of DMPs exhibit anti-entropic effects, opposing this direction of change. While changes in cell type composition minimally affect DMPs, VMPs and entropy measurements are moderately sensitive to such alterations.
conclusionThis study represents the largest investigation to date of genome-wide DNA methylation changes and aging in a single tissue, providing valuable insights into primary molecular changes relevant to chronological and biological aging.
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