| Title: | Accelerated biological aging and the risk of incident liver cancer: a prospective cohort study of the UK biobank |
| Journal: | BMC Gastroenterology |
| Published: | 20 Jul 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42477571/ |
| DOI: | https://doi.org/10.1186/s12876-026-05103-x |
Publication 21349
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Abstract
BackgroundWhile conventional risk factors for liver cancer are well-established, the contribution of biological aging to hepatocarcinogenesis remains poorly understood, representing an important gap in its etiological framework.MethodsWe conducted a prospective cohort study using data from the UK Biobank (UKB). Biological age (BA) was assessed using the Klemera-Doubal method (KDM-BA) and PhenoAge algorithms. Multivariable Cox proportional hazards models were used to evaluate associations between BA acceleration and liver cancer incidence, with robustness assessed using restricted cubic splines, subgroup analyses, and sensitivity analyses. Mediation analyses evaluated whether alanine aminotransferase (ALT) and aspartate aminotransferase (AST) mediate the relationship between biological aging and liver cancer.ResultsThe study included 274,966 participants (mean age 55.75 ± 8.10 years; 53.8% female). Over a median follow-up of 14.67 years, 325 incident liver cancer cases were documented. After multivariable adjustment, each 1-standard deviation (SD) increase in BA acceleration was associated with an elevated liver cancer risk (KDM-BA acceleration: HR = 1.28, 95%CI 1.16-1.41; PhenoAge acceleration: HR = 1.32, 95%CI 1.22-1.43). A nonlinear dose-response relationship was observed between KDM-BA acceleration and liver cancer risk (P < 0.001). Exploratory mediation analyses indicated that the effect of KDM-BA acceleration may be partially mediated by ALT and AST, whereas PhenoAge acceleration appeared to act primarily through direct mechanisms.ConclusionsAccelerated biological aging, as quantified by KDM-BA and PhenoAge, appears to be independently associated with incident liver cancer. The underlying pathways may differ: KDM-BA acceleration is partially mediated by liver enzymes, while PhenoAge acceleration appears to operate largely through direct mechanisms.</p>
5 Authors
- Xiaojuan Liu
- Shuangshuang Yang
- Conghui Zhang
- Ping Chen
- Jiangping Li
1 Application
| Application ID | Title |
|---|---|
| 98124 | Understanding the patterns of multimorbidity, and the role of environmental, lifestyle-related, psychological and genetic factors |
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