ArticleScientific reports2021
Disentangling age-dependent DNA methylation: deterministic, stochastic, and nonlinear.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-analysis of DNA methylation aging signatures in 17 human tissues.Nature aging · 2026Pooled it
- LINE-1 CpG methylation in canine blood and cortical DNA tracks epigenetic changes with age.GeroScience · 2026Article
- Embracing non-linearity in human ageing.Nature reviews. Genetics · 2026Review
- A unifying model of stem cell dynamics explains age-related methylation patterns across mammals.Nature aging · 2026Article
- Article
- Sex-specific nonlinear DNA methylation aging trajectories reveal biomarkers of cancer risk and inflammation.Genome biology · 2026Article
- Methods for analysing wildlife DNA methylation data.Conservation physiology · 2026Article
- Pathway information on methylation analysis using deep neural network (PROMINENT): An interpretable deep learning method with pathway prior for phenotype prediction using gene-level DNA methylation.Artificial intelligence in medicine · 2025Article
- MskAge-An Epigenetic Biomarker of Musculoskeletal Age Derived From a Genetic Algorithm Islands Model.Aging cell · 2025Article
- Quiescence Multiverse.Biomolecules · 2025Review
- Weighted 2D-kernel density estimations provide a new probabilistic measure for epigenetic age.Genome biology · 2025Article
- Age-related changes in DNA methylation in a sample of elderly Brazilians.Clinical epigenetics · 2025Article
- Nonlinear dynamics of multi-omics profiles during human aging.Nature aging · 2024Article
- Unveiling the molecular landscape of cognitive aging: insights from polygenic risk scores, DNA methylation, and gene expression.Human genomics · 2024Article
- Nature of epigenetic aging from a single-cell perspective.Nature aging · 2024Article
- Aging clocks based on accumulating stochastic variation.Nature aging · 2024Article
- Nonlinear DNA methylation trajectories in aging male mice.Nature communications · 2024Article
- Insights into ageing rates comparison across tissues from recalibrating cerebellum DNA methylation clock.GeroScience · 2024Article
- Aging differentially alters the transcriptome and landscape of chromatin accessibility in the male and female mouse hippocampus.Frontiers in molecular neuroscience · 2024Article
- An epigenome-wide analysis of sex hormone levels and DNA methylation in male blood samples.Epigenetics · 2023Article
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5 authors.
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Abstract
DNA methylation variability arises due to concurrent genetic and environmental influences. Each of them is a mixture of regular and noisy sources, whose relative contribution has not been satisfactorily understood yet. We conduct a systematic assessment of the age-dependent methylation by the signal-to-noise ratio and identify a wealth of "deterministic" CpG probes (about 90%), whose methylation variability likely originates due to genetic and general environmental factors. The remaining 10% of "stochastic" CpG probes are arguably governed by the biological noise or incidental environmental factors. Investigating the mathematical functional relationship between methylation levels and variability, we find that in about 90% of the age-associated differentially methylated positions, the variability changes as the square of the methylation level, whereas in the most of the remaining cases the dependence is linear. Furthermore, we demonstrate that the methylation level itself in more than 15% cases varies nonlinearly with age (according to the power law), in contrast to the previously assumed linear changes. Our findings present ample evidence of the ubiquity of strong DNA methylation regulation, resulting in the individual age-dependent and nonlinear methylation trajectories, whose divergence explains the cross-sectional variability. It may also serve a basis for constructing novel nonlinear epigenetic clocks.
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