Blood transcriptomic associations of epigenetic age in adolescents

Dennis Khodasevich; Anne K Bozack; Saher Daredia; Julianna Deardorff; Kim G Harley; Brenda Eskenazi; Weihong Guo; Nina Holland; Andres Cardenas

doi:10.1080/15592294.2025.2503824

Epigenetics (Dec 2025)

Blood transcriptomic associations of epigenetic age in adolescents

Dennis Khodasevich,
Anne K Bozack,
Saher Daredia,
Julianna Deardorff,
Kim G Harley,
Brenda Eskenazi,
Weihong Guo,
Nina Holland,
Andres Cardenas

Affiliations

Dennis Khodasevich: Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA
Anne K Bozack: Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA
Saher Daredia: Division of Epidemiology, Berkeley Public Health, University of California, Berkeley, CA, USA
Julianna Deardorff: Center for Environmental Research and Community Health (CERCH), Berkeley Public Health, University of California, Berkeley, CA, USA
Kim G Harley: Center for Environmental Research and Community Health (CERCH), Berkeley Public Health, University of California, Berkeley, CA, USA
Brenda Eskenazi: Center for Environmental Research and Community Health (CERCH), Berkeley Public Health, University of California, Berkeley, CA, USA
Weihong Guo: Center for Environmental Research and Community Health (CERCH), Berkeley Public Health, University of California, Berkeley, CA, USA
Nina Holland: Center for Environmental Research and Community Health (CERCH), Berkeley Public Health, University of California, Berkeley, CA, USA
Andres Cardenas: Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA

DOI: https://doi.org/10.1080/15592294.2025.2503824
Journal volume & issue: Vol. 20, no. 1

Abstract

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Epigenetic aging in early life remains poorly characterized, and patterns of gene expression can provide biologically meaningful insights. Blood DNA methylation was measured using the Illumina EPICv1.0 array and RNA sequencing was performed in blood in 174 adolescent participants (age range: 14–15 years) from the CHAMACOS cohort. Thirteen widely used epigenetic clocks were calculated, and their associations with transcriptome-wide RNA expression were tested using the limma-voom pipeline. We found evidence for substantial shared associations with RNA expression between different epigenetic clocks, including differential expression of MYO6 and ZBTB38 across five clocks. The epiTOC2, principal component (PC) PhenoAge, Hannum, PedBE and PC Hannum clocks were associated with differential expression of the highest number of RNAs, exhibiting associations with 22, 8, 5, 3, and 2 transcripts respectively. Generally, biological clocks were associated with differential expression of more genes than chronological clocks, and PC clocks were associated with differential expression of more genes relative to their CpG-trained counterparts. A total of 17 associations in our study were replicated in an independent adult sample (age range: 40–54 years). Our findings support the biological relevance of epigenetic clocks in adolescents and provide direction for selection of epigenetic ageing biomarkers in adolescent research.

Published in Epigenetics

ISSN: 1559-2294 (Print); 1559-2308 (Online)
Publisher: Taylor & Francis Group
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General): Genetics
Website: https://www.tandfonline.com/kepi

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