DNA methylation variability provides a distinct epigenetic marker of human aging heterogeneity
Combining methylation variance with mean methylation levels improved predictions of all-cause mortality across two independent human cohorts.
bioRxiv : the preprint server for biology · Vishnyakova O et al. · Paper published 25 Sep 2026
In a preprint analyzing blood samples from 1,445 Canadians aged 45 to 85 in the Canadian Longitudinal Study on Aging, researchers examined how DNA methylation variance relates to aging heterogeneity. The team performed epigenome-wide differential methylation and variance association analyses alongside measures of frailty, cognitive function, and physical function. They identified 448 differentially methylated regions and 488 differentially variable regions associated with health decline. These two groups of regions showed minimal overlap. Differentially methylated regions were enriched for immune and inflammation pathways, while differentially variable regions captured CpG island-enriched signals shared across health domains. Combining sites from both analyses produced an epigenetic biomarker linked to all-cause mortality. This combined marker showed higher discrimination than either measure alone, an outcome the authors reproduced in the Baltimore Longitudinal Study of Aging.
Why it matters
DNA methylation variability tracks biological dysregulation distinct from average methylation shifts. Accounting for this variance can reveal complementary epigenetic signals underlying differences in how individuals age.
Caveats
This observational study is a preprint that has not yet been peer-reviewed. The authors note the need for further validation in larger cohorts that include more mortality events.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
DNA methylation variability provides a complementary epigenetic signature of aging heterogeneity: Findings from the Canadian Longitudinal Study on Aging and the Baltimore Longitudinal Study of Aging
Vishnyakova O, Min J, Moore AZ et al.
bioRxiv : the preprint server for biology · 25 Sep 2026 · Preprint, not yet peer-reviewed
- Relevance
- Core geroscience
- News value
- Important
- Evidence
- Humans
- Status
- Preprint
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