Prospective association between biological aging and risk of hospital-diagnosed MASLD: evidence from the UK Biobank.

Xue Yang, Sicheng Li, Qingping Xue, Peijing Yan, Qian Li, Yi Gong, Xiayue Fan, Wenzhi Zhu, Shiyi Wu, Shanshan Zhang, Ko Willems van Dijk, Patrick C N Rensen, Ruifang Li-Gao, Yanan Wang, Ting Yao

Journal: Frontiers in endocrinology 2026;17():1853319

PMID: 42388879

View on PubMed

Abstract

BACKGROUND AND AIMS

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder linked to increased all-cause and cardiovascular mortality. While accelerated biological aging is a known risk factor for age-related diseases, its role in MASLD remains unclear. This study explores the association between biological aging and hospital-diagnosed MASLD and investigates the potential mediating effects of biological aging on lifestyle-MASLD relationships.

METHODS AND RESULTS

Data were from the UK Biobank, and the biological age was estimated by PhenoAge and Klemera-Doubal method age (KDMAge). The association between biological aging and hospital-diagnosed MASLD (defined as hospital admission or death) was estimated using Cox regression. Biological aging acceleration was defined as positive residuals obtained from regressing biological age on chronological age. Mediation analyses were used to assess the potential mediating role of biological aging in the relationships between lifestyle and hospital-diagnosed MASLD. Among 247,444 participants, 3,254 developed hospital-diagnosed MASLD during a median follow-up of 13.7 years. Accelerated biological aging was significantly associated with hospital-diagnosed MASLD with hazard ratios of 1.46 (95% confidence interval, 1.35, 1.57) for PhenoAge acceleration and 1.35 (1.19, 1.53) for KDMAge acceleration. In mediation analyses, PhenoAge acceleration significantly accounted for the associations between four unhealthy lifestyle factors (smoking, drinking, poor diet, and low physical activity) and MASLD, with mediation proportions ranging from 11.4% to 25.5%, and the strongest effect observed for smoking. In contrast, KDMAge acceleration showed minimal mediation effects (≤2%).

CONCLUSIONS

Accelerated biological aging was associated with hospital-diagnosed MASLD and may partially mediate the associations between unhealthy lifestyles and hospital-diagnosed MASLD. These findings support the potential relevance of biological aging in MASLD risk stratification and prevention.

Address: Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.; Med-X Institute, Center for Immunological and Metabolic Diseases, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.; Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.; Department of Epidemiology and Biostatistics, School of Public Health, Chengdu Medical College, Chengdu, Sichuan, China.; Clinical Research Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.; Med-X Institute, Center for Immunological and Metabolic Diseases, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.; Department of Healthcare-associated Infection Management, Chengdu Hi-Tech Zone Hospital for Women and Children (Chengdu Hi-Tech Zone Hospital for Maternal and Child Healthcare), Chengdu, Sichuan, China.; Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.; Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands.; Department of Medicine, Division of Endocrinology, and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands.; Med-X Institute, Center for Immunological and Metabolic Diseases, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.; Department of Medicine, Division of Endocrinology, and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands.; Department of Clinical Epidemiology, C7-P, Leiden University Medical Center, Leiden, Netherlands.; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.

DOI: 10.3389/fendo.2026.1853319

MeSH Terms: Humans, Aging, United Kingdom, Female, Male, Aged, Risk Factors, Fatty Liver, Prospective Studies, Biological Specimen Banks, Middle Aged, UK Biobank, Life Style, Hospitalization