Age-related dynamics of DNA co-methylation modules in humans
- 1Institute of Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
Abstract
Age-related changes in the mean or variance of DNA methylation (DNAm) at individual CpG sites are well established. However, CpGs that share biological functions often exhibit coordinated regulation. Here, we analysed whole-blood DNAm data from over 7,500 individuals and identified modules of co-methylated CpGs that either maintain consistent correlations with age (age-stable modules) or undergo age-related remodelling (age-variable modules). We show that co-methylation modules are largely preserved during healthy aging, with only a small subset (~15%) showing substantial age-related reorganisation. Age-stable modules are enriched for CpG loci within promoters, transcription start sites, and CpG islands, whereas age-variable modules harbour loci that are depleted in these genomic domains and enriched for repressive chromatin marks. Age-stable co-methylation modules are also associated with long-range genetic regulation (trans-meQTLs), promoter-associated chromatin states, and higher-order chromatin interactions. While both age-stable and age-variable modules are enriched for developmental pathways, immune-related processes are distinctly associated with age-stable modules. Overall, our findings suggest that epigenetic aging is characterised by a spectrum of co-methylation network trajectories, ranging from stability to disruption, shaped by underlying genomic regulatory architecture.
Related
- Characterization of DNA methylation in PBMCs and donor-matched iPSCs shows age-related methylation is reset during stem cell reprogramming
- Modifiable glymphatic-related brain clearance physiology in humans: a critical narrative review of interventional evidence
- Multi-Methodological Characterization of Sleep Deprivation: From Standard EEG Power Spectra to Aperiodic Dynamics in Humans and Mice.
- Physiological and health-related effects of 5G-relevant radiofrequency fields: A systematic review of experimental studies in humans and mammals
- Shared symmetry detection with divergent temporal dynamics in marmosets and humans
BibTeX
@misc{cheruiyot2026agerelated,
title = {{Age-related dynamics of DNA co-methylation modules in humans}},
author = {E. K. Cheruiyot and A. A. Hatton and D. L. McCartney and R. E. Marioni and A. F. McRae},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.13.751212},
url = {https://www.biorxiv.org/content/10.64898/2026.09.13.751212v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Age-related dynamics of DNA co-methylation modules in humans
AU - E. K. Cheruiyot
AU - A. A. Hatton
AU - D. L. McCartney
AU - R. E. Marioni
AU - A. F. McRae
PY - 2026
DA - 2026/09/13
PB - bioRxiv
DO - 10.64898/2026.09.13.751212
UR - https://www.biorxiv.org/content/10.64898/2026.09.13.751212v1
AB - Age-related changes in the mean or variance of DNA methylation (DNAm) at individual CpG sites are well established. However, CpGs that share biological functions often exhibit coordinated regulation. Here, we analysed whole-blood DNAm data from over 7,500 individuals and identified modules of co-methylated CpGs that either maintain consistent correlations with age (age-stable modules) or undergo age-related remodelling (age-variable modules). We show that co-methylation modules are largely preserved during healthy aging, with only a small subset (~15%) showing substantial age-related reorganisation. Age-stable modules are enriched for CpG loci within promoters, transcription start sites, and CpG islands, whereas age-variable modules harbour loci that are depleted in these genomic domains and enriched for repressive chromatin marks. Age-stable co-methylation modules are also associated with long-range genetic regulation (trans-meQTLs), promoter-associated chromatin states, and higher-order chromatin interactions. While both age-stable and age-variable modules are enriched for developmental pathways, immune-related processes are distinctly associated with age-stable modules. Overall, our findings suggest that epigenetic aging is characterised by a spectrum of co-methylation network trajectories, ranging from stability to disruption, shaped by underlying genomic regulatory architecture.
ER -