Epigenetic signature of heterogeneity in aging: Findings from the Canadian Longitudinal Study on Aging Article Swipe
Olga Vishnyakova
,
Joosung Min
,
Xiaowei Song
,
Kenneth Rockwood
,
Angela Brooks‐Wilson
,
Lloyd T. Elliott
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.08.25.671156
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.08.25.671156
Human aging does not follow a single trajectory. Epigenetic changes offer insight into the heterogeneity in aging by reflecting the combined influence of genetic, environmental, and lifestyle factors on the timing and progression of age-related changes beyond what chronological age alone can explain. Emerging research in cancer and aging highlights the importance of methylation variability as a marker of biological disruption. It also shows that there is little overlap between CpGs differing in means versus variability. We investigated the role of DNA methylation in aging heterogeneity by performing epigenome-wide differential methylation and variance association analysis in blood samples from 1,445 Canadians aged 45 to 85. We identified 448 differentially methylated regions (DMRs) and 488 differentially variable regions (DVRs) associated with health decline as measured by health deficit accumulation (i.e. the Frailty Index), cognitive, and physical function. We observed minimal overlap between these types of regions, with distinct genes, highlighting a unique and potentially additional contribution of variability to age-related epigenetic changes. Gene ontology analyses of DMRs revealed enrichment in immune and inflammation-related pathways pointing to immune function as a key driver of aging heterogeneity. By integrating significant regions from both analyses, we constructed a composite epigenetic biomarker. Our biomarker outperformed control models built on differential methylation alone as well as established epigenetic biomarkers (e.g. GrimAge, PhenoAge) in predicting mortality and the onset of chronic obstructive pulmonary disease.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.08.25.671156
- https://www.biorxiv.org/content/biorxiv/early/2025/08/27/2025.08.25.671156.full.pdf
- OA Status
- green
- References
- 48
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4413800009
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4413800009Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2025.08.25.671156Digital Object Identifier
- Title
-
Epigenetic signature of heterogeneity in aging: Findings from the Canadian Longitudinal Study on AgingWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-08-27Full publication date if available
- Authors
-
Olga Vishnyakova, Joosung Min, Xiaowei Song, Kenneth Rockwood, Angela Brooks‐Wilson, Lloyd T. ElliottList of authors in order
- Landing page
-
https://doi.org/10.1101/2025.08.25.671156Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2025/08/27/2025.08.25.671156.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
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-
greenOpen access status per OpenAlex
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-
https://www.biorxiv.org/content/biorxiv/early/2025/08/27/2025.08.25.671156.full.pdfDirect OA link when available
- Concepts
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Epigenetics, Signature (topology), Longitudinal data, Cellular Aging, Longitudinal study, Cognitive aging, Successful aging, Psychology, Evolutionary biology, Biology, Genetics, Gerontology, Medicine, Demography, Neuroscience, Sociology, Gene, Mathematics, Pathology, Cognition, Telomere, GeometryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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48Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W2889294609, https://openalex.org/W2990428470, https://openalex.org/W2724383163, https://openalex.org/W2152656267, https://openalex.org/W2125700595, https://openalex.org/W4390618866, https://openalex.org/W2165101781, https://openalex.org/W2080644309, https://openalex.org/W2134555277, https://openalex.org/W2105767248, https://openalex.org/W2039669402, https://openalex.org/W1974047233, https://openalex.org/W2121091193, https://openalex.org/W4405716356, https://openalex.org/W2949100461, https://openalex.org/W2912654909, https://openalex.org/W3022131036, https://openalex.org/W3201585688, https://openalex.org/W2167287693, https://openalex.org/W2152434143, https://openalex.org/W1982344226, https://openalex.org/W2125154191, https://openalex.org/W2053846901, https://openalex.org/W2972265869, https://openalex.org/W2944944066, https://openalex.org/W4403781665, https://openalex.org/W2130752875, https://openalex.org/W4293052083, https://openalex.org/W2944524138, https://openalex.org/W2153860431, https://openalex.org/W1963480915, https://openalex.org/W3185274815, https://openalex.org/W4385718617, https://openalex.org/W2159662576, https://openalex.org/W2157068721, https://openalex.org/W4401724571, https://openalex.org/W2142459690, https://openalex.org/W2130523009, https://openalex.org/W4220691247, https://openalex.org/W1975528145, https://openalex.org/W2105092978, https://openalex.org/W2146512944, https://openalex.org/W2123929789, https://openalex.org/W2261451134, https://openalex.org/W4294541781, https://openalex.org/W4389295970, https://openalex.org/W3126160703, https://openalex.org/W2950099124 |
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