| Title: | Accelerated biological aging and underlying epigenetic modification mediated the association between obesity and asthma |
| Journal: | Clinical Epigenetics |
| Published: | 21 May 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42169188/ |
| DOI: | https://doi.org/10.1186/s13148-026-02145-6 |
Publication 19970
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Abstract
BackgroundThe relationships among obesity, accelerated biological aging, and asthma, as well as the underlying epigenetic mechanisms, remain incompletely understood.MethodsWe conducted a prospective cohort study in the UK Biobank to evaluate whether accelerated biological aging mediates the association between obesity and incident asthma. We then performed two-sample Mendelian randomization (MR) to assess the potential causal effect of accelerated biological aging on asthma from an epigenetic perspective. Epigenetic MR and colocalization analyses were used to prioritize aging-related DNA methylation (DNAm) CpG sites associated with asthma. Finally, single-cell RNA sequencing (scRNA-seq) was applied to characterize the cell-type-specific expression patterns of CpG-mapped genes.ResultsIn the UK Biobank cohort, KDM-BA acceleration and PhenoAge acceleration partially mediated the association between obesity and asthma, with proportions mediated of 4.0% and 12.2%, respectively. Two-sample MR further suggested that DNAm PhenoAge acceleration was associated with a higher risk of asthma (OR = 1.02; 95% CI: 1.01-1.03; P = 0.004). Epigenetic MR and colocalization analyses suggested that cg02010481 (JAZF1), cg17929770 (RSPH6A), cg19927816 (SYMPK; RSPH6A), cg08544331 (RUNX3), cg15498134 (RUNX3), and cg04389704 (FBXL19) were associated with a reduced risk of asthma, whereas cg16553500 (COL16A1), cg16351569, cg10036013 (FOXK1), cg11647481 (FOXK1), cg23776012 (KRT222), and cg08258403 were associated with an increased risk of asthma. In scRNA-seq analyses, JAZF1, SYMPK, FOXK1, and RUNX3 were differentially expressed across multiple immune cell types.ConclusionsThis study demonstrates that accelerated biological aging partially mediates the association of obesity with asthma and further elucidates underlying epigenetic mechanisms linking aging to asthma.</p>
7 Authors
- Jian Liu
- Zhengqi Song
- Chengge Shi
- Xinan Lu
- Aijun Zhang
- Yihe Chen
- Xuejia Zhang
1 Application
| Application ID | Title |
|---|---|
| 775083 | Multidimensional interplay in cardiovascular and metabolic diseases pathogenesis via multi-omics analysis and modifiable risks |
Enabling scientific discoveries that improve human health