Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: Epigenetic marks are encoded by DNA methylation and accumulate errors as organisms age. This drift correlates with lifespan, but the biology of how this occurs is still unexplained. We analyze DNA methylation with age in mouse intestinal stem cells and compare them to nonstem cells.
Results: Age-related changes in DNA methylation are identical in stem and nonstem cells, affect most prominently CpG islands and correlate weakly with gene expression. Age-related DNA methylation entropy, measured by the Jensen-Shannon Distribution, affects up to 25% of the detectable CpG sites and is a better measure of aging than individual CpG methylation. We analyze this entropy as a function of age in seven other tissues (heart, kidney, skeletal muscle, lung, liver, spleen, and blood) and it correlates strikingly with tissue-specific stem cell division rates. Thus, DNA methylation drift and increased entropy with age are primarily caused by and are sensors for, stem cell replication in adult tissues.
Conclusions: These data have implications for the mechanisms of tissue-specific functional declines with aging and for the development of DNA-methylation-based biological clocks.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933260 | PMC |
| http://dx.doi.org/10.1186/s13059-023-02866-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
TCA cycle-derived oncometabolites in cancer and the immune microenvironment.
J Biomed Sci
September 2025
Division of Gastroenterology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Oncometabolites are aberrant metabolic byproducts that arise from mutations in enzymes of the tricarboxylic acid (TCA) cycle or related metabolic pathways and play central roles in tumor progression and immune evasion. Among these, 2-hydroxyglutarate (2-HG), succinate, and fumarate are the most well-characterized, acting as competitive inhibitors of α-ketoglutarate-dependent dioxygenases to alter DNA and histone methylation, cellular differentiation, and hypoxia signaling. More recently, itaconate, an immunometabolite predominantly produced by activated macrophages, has been recognized for its dual roles in modulating inflammation and tumor immunity.
View Article and Find Full Text PDFThe impact of melatonin-enriched media on epigenetic and perinatal changes induced by embryo culture in a mouse model.
J Assist Reprod Genet
September 2025
Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
Purpose: To determine if melatonin-enriched culture media could offset loss of imprinting in mouse concepti.
Methods: Zygotes were cultured to blastocyst stage under optimized conditions in melatonin-supplemented media at either 10 M (MT 10) or 10 M (MT 10), or without supplementation (Culture + embryo transfer, or ET, positive control). Blastocysts were also developed in vivo (ET negative control).
DNA methylation cooperates with genomic alterations during non-small cell lung cancer evolution.
Nat Genet
September 2025
Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Aberrant DNA methylation has been described in nearly all human cancers, yet its interplay with genomic alterations during tumor evolution is poorly understood. To explore this, we performed reduced representation bisulfite sequencing on 217 tumor and matched normal regions from 59 patients with non-small cell lung cancer from the TRACERx study to deconvolve tumor methylation. We developed two metrics for integrative evolutionary analysis with DNA and RNA sequencing data.
View Article and Find Full Text PDFFluctuating DNA methylation tracks cancer evolution at clinical scale.
Nature
September 2025
Centre for Evolution and Cancer, Institute of Cancer Research, London, UK.
Cancer development and response to treatment are evolutionary processes, but characterizing evolutionary dynamics at a clinically meaningful scale has remained challenging. Here we develop a new methodology called EVOFLUx, based on natural DNA methylation barcodes fluctuating over time, that quantitatively infers evolutionary dynamics using only a bulk tumour methylation profile as input. We apply EVOFLUx to 1,976 well-characterized lymphoid cancer samples spanning a broad spectrum of diseases and show that initial tumour growth rate, malignancy age and epimutation rates vary by orders of magnitude across disease types.
View Article and Find Full Text PDFForensic applications of compound genetic markers: trends and future directions.
Sci Justice
September 2025
School of Life Sciences, University of KwaZulu-Natal, Private Bag X54001, Westville, Durban 4000, South Africa. Electronic address:
A compound marker integrates two or more genetic markers into a single assay. The application of compound markers enhances the predictive accuracy of genetic testing by leveraging the strengths of different genetic variations while mitigating the limitations of individual markers. Compound markers include SNP-SNPs, SNP-STRs, DIP-SNPs, DIP-STRs, Multi-In/Dels, CpG-SNPs, CpG-STRs/CpG-In/Del, and Methylation-Microhaplotypes.
View Article and Find Full Text PDF