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

Xue Yang1,2, Sicheng Li3, Qingping Xue4

  • 1Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Frontiers in Endocrinology
|July 2, 2026
PubMed
Abstract

Insights

Accelerated biological aging increases the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Biological aging partially explains how unhealthy lifestyles, like smoking, contribute to MASLD development.

Area of Science:

  • Gerontology
  • Hepatology
  • Metabolic Diseases

Background:

  • Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition linked to higher mortality rates.
  • Accelerated biological aging is a risk factor for various age-related diseases, but its connection to MASLD is not well understood.

Purpose of the Study:

  • To investigate the association between accelerated biological aging and hospital-diagnosed MASLD.
  • To determine if biological aging mediates the relationship between lifestyle factors and MASLD.

Main Methods:

  • Utilized UK Biobank data from 247,444 participants with a median follow-up of 13.7 years.
  • Estimated biological age using PhenoAge and Klemera-Doubal method age (KDMAge).
  • Employed Cox regression and mediation analyses to assess associations and mediation effects.

Main Results:

  • Accelerated biological aging (PhenoAge and KDMAge) was significantly associated with increased risk of hospital-diagnosed MASLD.
  • PhenoAge acceleration partially mediated the link between unhealthy lifestyles (smoking, drinking, poor diet, low physical activity) and MASLD, accounting for 11.4%-25.5% of the effect.
  • KDMAge acceleration showed minimal mediation effects.

Conclusions:

  • Accelerated biological aging is a significant risk factor for MASLD.
  • Biological aging may partially explain the impact of unhealthy lifestyles on MASLD development.
  • These findings highlight the potential role of biological aging in MASLD risk assessment and prevention strategies.
Keywords:
MASLDage accelerationbiological aginglifestylemediation

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