ArticleNature aging2025
Iron homeostasis and cell clonality drive cancer-associated intestinal DNA methylation drift in aging.
Article in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
6 citing papers in PubMed.
- Review
- Epigenetic clocks as quantitative readouts of epigenetic drift.Nature aging · 2026Article
- Review
- Gut microbiota-epigenetic interactions in systemic aging: mechanistic drivers for endocrine and reproductive network remodeling and therapeutic modulation.Frontiers in aging · 2026Review
- Mechanistic redundancy and hierarchy of aging mechanisms: implications for strategies to extend healthspan and biomarker integration.Frontiers in aging · 2026Review
- Revealing epigenetic drift in intestinal pathogenesis with age.Nature aging · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epigenetic drift is a key feature of aging and is associated with age-related diseases including cancer, yet the underlying molecular mechanisms remain unclear. Here, by analyzing DNA methylation and gene expression data from healthy and cancerous human colon samples, we identify an aging and colon cancer-associated DNA methylation (DNAm) drift. We find evidence that this drift is conserved in the mouse intestinal epithelium, where we demonstrate its origin within intestinal stem cells and identify its cell-intrinsic and non-mitotic characteristics, finding that its expansion is regulated via crypt clonality and fission. Mechanistically, we find that this drift is driven by age-related inflammation and reduced Wnt signaling, which dysregulate iron metabolism and impair TET activity. Despite CpG-level heterogeneity, we find that DNAm changes are consistent at the gene level, suggesting potential functionality. Our findings shed light on the epigenetic mechanisms of aging and provide a mechanistic basis for the hypermethylation observed in cancer.
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Registered trials
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