ArticleClinical epigenetics2023
The inactive X chromosome accumulates widespread epigenetic variability with age.
Article in Clinical epigenetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Peripheral and Central miRNA Signatures in Alzheimer's Disease: Tissue-Specific Variability, Sex-Associated Differences, and Implications for Blood-Based Biomarkers.International journal of molecular sciences · 2026Review
- Identification of SENP7 and UTF1/VENTX as new loci influencing clustered protocadherin methylation across blood and brain using a genome-wide association study.Molecular psychiatry · 2026Article
- Epigenetic drift score captures directional methylation variability and links aging to transcriptional, metabolic, and genetic alterations.Genome research · 2025Article
- Escape of Kdm6a from X Chromosome Is Detrimental to Ischemic Brains via IRF5 Signaling.Translational stroke research · 2025Article
- Strategies for studying sex differences in brain aging.Trends in genetics : TIG · 2025Review
- Improved epigenetic age prediction models by combining sex chromosome and autosomal markers.Epigenetics & chromatin · 2025Article
- Aging promotes reactivation of the Barr body at distal chromosome regions.Nature aging · 2025Article
- DNA Methylation Dynamics Reflect Sex and Status Differences in Mortality Rates in a Polygynous Bat.Molecular ecology · 2025Article
- Aging activates escape of the silent X chromosome in the female mouse hippocampus.Science advances · 2025Article
- Age-Dependent DNA Methylation Variability on the X-Chromosome in Male and Female Twins.Epigenomes · 2024Article
- Multifaceted role of CTCF in X-chromosome inactivation.Chromosoma · 2024Review
- Escape of Kdm6a from X chromosome is detrimental to ischemic brains via IRF5 signaling.Research square · 2024Article
- Sex-specific modulation of renal epigenetic and injury markers in aging kidney.American journal of physiology. Renal physiology · 2024Article
- Altered X-chromosome inactivation predisposes to autoimmunity.Science advances · 2024Article
- Sex-Biased Expression and Response of microRNAs in Neurological Diseases and Neurotrauma.International journal of molecular sciences · 2024Review
- Role of sex in immune response and epigenetic mechanisms.Epigenetics & chromatin · 2024Review
- Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLoss of epigenetic control is a hallmark of aging. Among the most prominent roles of epigenetic mechanisms is the inactivation of one of two copies of the X chromosome in females through DNA methylation. Hence, age-related disruption of X-chromosome inactivation (XCI) may contribute to the aging process in women.
methodsWe analyzed 9,777 CpGs on the X chromosome in whole blood samples from 2343 females and 1688 males (Illumina 450k methylation array) and replicated findings in duplicate using one whole blood and one purified monocyte data set (in total, 991/924 females/males). We used double generalized linear models to detect age-related differentially methylated CpGs (aDMCs), whose mean methylation level differs with age, and age-related variably methylated CpGs (aVMCs), whose methylation level becomes more variable with age.
resultsIn females, aDMCs were relatively uncommon (n = 33) and preferentially occurred in regions known to escape XCI. In contrast, many CpGs (n = 987) were found to display an increased variance with age (aVMCs). Of note, the replication rate of aVMCs was also high in purified monocytes (94%), indicating an independence of cell composition. aVMCs accumulated in CpG islands and regions subject to XCI suggesting that they stemmed from the inactive X. In males, carrying an active copy of the X chromosome only, aDMCs (n = 316) were primarily driven by cell composition, while aVMCs replicated well (95%) but were infrequent (n = 37).
conclusionsOur results imply that age-related DNA methylation differences at the inactive X chromosome are dominated by the accumulation of variability.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.