| Title: | High cardiorespiratory fitness is associated with younger brain age: the role of systemic inflammation |
| Journal: | Brain Behavior and Immunity |
| Published: | 19 May 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42162798/ |
| DOI: | https://doi.org/10.1016/j.bbi.2026.106817 |
Publication 19997
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Abstract
OBJECTIVES: To examine the relationship between cardiorespiratory fitness (CRF) and brain aging, and the extent to which this is mediated by systemic inflammation.</p>
METHODS: This study included 4,770 adults from the UK Biobank (mean age: 55.37 ± 7.50 years) at baseline, who underwent structural and functional brain magnetic resonance imaging (MRI) at a follow-up examination conducted an average of 8.9 years after the baseline. CRF was estimated from a 6-minute submaximal exercise test on a stationary bike and expressed as age- and sex-standardized tertiles (i.e., low, moderate, and high). Brain age was estimated using a machine learning model based on 1,079 brain MRI phenotypes. Low-grade inflammation was quantified using four inflammatory biomarkers with standard assessment. Data were analyzed using linear regressions and generalized structural equation models.</p>
RESULTS: At baseline, standardized CRF z-scores ranged from -2.59 to 26.60. Compared to participants with low CRF, those with high CRF had younger brain age than chronological age (β = - 0.52 [95 % confidence interval: -0.92, -0.13]). High CRF was associated with lower inflammation (β = - 2.75 [-3.16, -2.34]), which in turn was associated with younger brain age (β = - 0.05 [-0.08, -0.02]). In the mediation analysis, lower inflammation mediated 20.65 % (P = 0.005) of the associations between high CRF and younger brain age.</p>
CONCLUSION: High CRF is associated with a younger brain age, and lower systemic inflammation partly mediates this association.</p>
7 Authors
- Jiao Wang
- Shuqi Wang
- Liying Zhang
- Zhanchen Dong
- David A Bennett
- Jirong Yue
- Weili Xu
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