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"A new DNA-methylation map could reveal anti-aging targets, a pre-print meta-analysis suggests. The study looked at epigenetic changes — namely methylation, the addition or removal of tags called methyl groups — in 17 human tissue types.
It revealed that some tissues, such as retina and stomach, accumulate age-related DNA changes faster than others. “This work looks into the functional relevance of the methylation, rather than just using it as a timepiece for ageing,” ... While most tissues gain methylation as they age, skeletal and lung tissue are the exception to the rule, the study found."
"The visible effects of ageing on our body are in part linked to invisible changes in gene activity. The epigenetic process of DNA methylation — the addition or removal of tags called methyl groups — becomes less precise as we age. The result is changes to gene expression that are linked to reduced organ function and increased susceptibility to disease as people age. ..."
From the 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⁺ salvage metabolism supports therapeutic targeting of NAD⁺ 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"
How ageing changes our genes — huge epigenetic atlas gives clearest picture yet "A map of DNA methylation changes in human organs could help researchers to discover more targets for anti-ageing therapies."
DNA Methylation Ageing Atlas Across 17 Human Tissues (preprint, open access)
Fig. 1 Differentially Methylated Positions (DMPs) with Age in 17 distinct human tissues. Each volcano plot depicts a unique tissue along with its methylation changes as one ages. Each dot corresponds to a distinct CpG, with colored dots indicating a significant association with age at an FDR <0.005, while gray dots signify CpGs that do not exhibit significant changes with age.
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