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DNA Methylation Ageing Atlas Across 17 Human Tissues

Jacques, M.; Seale, K.; Voisin, S.; Lysenko, A.; Grolaux, R.; Jones-Freeman, B.; Lamon, S.; Levinger, I.; Bauer, C.; Sharples, A. P.; Heikkinen, A.; Sillanpaa, E.; Ollikainen, M.; Smith, C.; Broatch, J. R.; Zarekookandeh, N.; Gillberg, L.; Blom, I.; Poganik, J. R.; Moqri, M.; Gladyshev, V.; Taper, M.; Malecki, C.; Lal, S.; Saurat, N.; Horvath, S.; Teschendorff, A.; EYNON, N.

2025-07-24 bioinformatics
10.1101/2025.07.21.665830 bioRxiv
Show abstract

Aging involves widespread epigenetic remodeling across tissues, yet the nature and consistency of these changes remain unclear. We conducted a meta-analysis of more than 15,000 human methylomes spanning 17 tissues, identifying both conserved and tissue-specific aging signatures. We examined linear changes via differentially methylated positions, variability shifts via variably methylated positions, and Shannon-entropy to capture methylation disorder. Network analysis revealed fragile co-methylation modules largely resistant to beneficial perturbation. Key disruptors, including PCDHGA1, MEST, HDAC4, and HOX genes, exacerbated aging signals across tissues. Notably, a resilient module enriched for NAD{square} salvage metabolism supports therapeutic targeting of NAD{square} in aging. PCDHGA1 emerged as a conserved cross-tissue driver, suggesting protocadherin-mediated adhesion plays a broader role in maintaining structural and signaling stability in multiple organ systems. Our open-access atlas provides a foundational resource for dissecting the molecular architecture of human aging and identifying testable targets for intervention, biomarkers, and translational epigenetic therapies.

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1
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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.