ArticleAging cell2021
Age patterns of intra-pair DNA methylation discordance in twins: Sex difference in epigenomic instability and implication on survival.
Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Modeling the effect of longitudinal markers on left-truncated time-to-event outcomes in twin studies.Statistical methods in medical research · 2025Article
- Gender and sex interactions are intrinsic components of cancer phenotypes.Nature reviews. Cancer · 2025Review
- Review
- Age-Dependent DNA Methylation Variability on the X-Chromosome in Male and Female Twins.Epigenomes · 2024Article
- Epigenetic developmental mechanisms underlying sex differences in cancer.The Journal of clinical investigation · 2024Review
- Article
- Age patterns of intra-pair DNA methylation discordance in twins: Sex difference in epigenomic instability and implication on survival.Aging cell · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Aging is a biological process linked to specific patterns and changes in the epigenome. We hypothesize that age-related variation in the DNA methylome could reflect cumulative environmental modulation to the epigenome which could impact epigenomic instability and survival differentially by sex. To test the hypothesis, we performed sex-stratified epigenome-wide association studies on age-related intra-pair DNA methylation discordance in 492 twins aged 56-80 years. We identified 3084 CpGs showing increased methylation variability with age (FDR < 0.05, 7 CpGs with p < 1e-07) in male twins but no significant site found in female twins. The results were replicated in an independent cohort of 292 twins aged 30-74 years with 37% of the discovery CpGs successfully replicated in male twins. Functional annotation showed that genes linked to the identified CpGs were significantly enriched in signaling pathways, neurological functions, extracellular matrix assembly, and cancer. We further explored the implication of discovery CpGs on individual survival in an old cohort of 224 twins (220 deceased). In total, 264 CpGs displayed significant association with risk of death in male twins. In female twins, 175 of the male discovery CpGs also showed non-random correlation with mortality. Intra-pair comparison showed that majority of the discovery CpGs have higher methylation in the longer-lived twins suggesting that loss of DNA methylation during aging contributes to increased risk of death which is more pronounced in male twins. In conclusion, age-related epigenomic instability in the DNA methylome is more evident in males than in females and could impact individual survival and contribute to sex difference in human lifespan.
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Registered trials
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.