# The role of healthy lifestyle in the association between hepatic fibro-inflammation and steatosis and brain aging—a cross-sectional study

**Authors:** Jikang Shi, Zhuoshuai Liang, Wenhui Gao, Huizhen Jin, Yinglin Du

PMC · DOI: 10.3389/fnagi.2026.1801577 · Frontiers in Aging Neuroscience · 2026-03-16

## TL;DR

This study found that liver fat and inflammation are linked to faster brain aging, but healthy lifestyles may reduce this effect.

## Contribution

The study shows that lifestyle factors can modify the link between liver health and brain aging.

## Key findings

- Liver fat and fibro-inflammation are associated with increased brain-predicted age difference (brain-PAD).
- Healthy lifestyle choices can reduce the impact of liver issues on brain aging.
- Fibro-inflammation has a stronger association with brain aging than liver fat alone.

## Abstract

This study investigated the association between liver fat, liver fibro-inflammation, and brain age, and assessed whether modifiable lifestyle factors modified the associations between liver markers and brain age.

A total of 19,566 adults free from dementia and other neurological disorders were included from the UK Biobank. Liver fat and fibro-inflammation were quantified using proton density fat fraction (PDFF) and iron-corrected T1 mapping (cT1) derived from liver MRI scans. Brain age was estimated using a machine learning model based on 1,079 brain MRI phenotypes, and brain-predicted age difference (brain-PAD) was calculated.

Among participants, 4,634 (23.7%) had significant steatotic liver disease (PDFF ≥ 5.5%), and 938 (4.8%) had significant fibro-inflammation (cT1 ≥ 800 ms). Both significant liver fat accumulation (β = 0.4, 95% CI: 0.21–0.59) and fibro-inflammation (β = 1.09, 95% CI: 0.74–1.44) were associated with increased brain-PAD. Joint exposure analysis showed that the association between liver fat/fibro-inflammation and increased brain-PAD was attenuated among individuals with healthy lifestyle choices.

Liver fat accumulation and fibro-inflammation were associated with higher brain-PAD, with fibro-inflammation playing a key role. These associations may be attenuated in individuals with optimal lifestyle behaviors, suggesting a potentially modifiable target for intervention.

## Linked entities

- **Diseases:** dementia (MONDO:0001627)

## Full-text entities

- **Diseases:** fibro-inflammation (MESH:D007249), steatosis (MESH:D005234), steatotic liver disease (MESH:D008107), neurological disorders (MESH:D009461), dementia (MESH:D003704), fat (MESH:D004620)
- **Chemicals:** iron (MESH:D007501)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13033754/full.md

## References

42 references — full list in the complete paper: https://tomesphere.com/paper/PMC13033754/full.md

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Source: https://tomesphere.com/paper/PMC13033754