Cross-sectional association between brain-derived neurotrophic factor and intrinsic capacity in older adults: The mediating role of oxidative stress

Objectives: Brain-derived neurotrophic factor (BDNF) is a key indicator in the brain-muscle axis. This study aimed to investigate the association of plasma BDNF and intrinsic capacity (IC) in older people, and to examine the mediating role of inflammation and oxidative stress. Methods: This cross-sectional study included 658 community-dwelling older adults (70.38 f 6.06 years, 59.42% female). Intrinsic capacity including five domains was evaluated according to the World Health Organization recommendation. Plasma BDNF, high sensitivity C-reactive protein (hs-CRP), Interleukin-6 (IL-6), Tumor necrosis factor-alpha (TNF-a), Interleukin-1 beta (IL-1(3), Malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione peroxidase (GSH-Px), and Glutathione reductase (GR)were measured by enzyme-linked immunosorbent assay methods. Restricted cubic spline and multivariate logistic regression were conducted to explore the association of BDNF with IC impairment. Mediation analyses were used to explore the potential mechanisms. Demographic characteristics, health behaviors, and comorbidities were included as covariates. Results: 247(37.54%) participants had IC impairment. Older individuals with impaired IC had lower levels of BDNF, IL-1(3, SOD, and GR, while showed higher levels of hs-CRP and MDA compared to the normal group. There was an Lshaped negative correlation between BDNF levels and the odds of IC impairment (P-nonlinear <0.001). After adjusting for all confounders, the odds for IC impairment in the medium and high BDNF tertiles were significantly lower than in the low BDNF tertile, with ORs of 0.43(95% CI: 0.26-0.89, P = 0.004) and 0.38(95% CI: 0.20-0.71, P = 0.007), respectively. Plasma SOD and GR mediated 4.13% (95% CI: 1.15, 7.16) and 7.82% (95% CI: 3.24, 12.48) of the total effect of BDNF on IC. Conclusion: High levels of circulatory BDNF may be related to lower odds of IC impairment. Oxidative stress status partially explains the mechanisms underlying the association. (c) 2025 The Author(s). Published by Elsevier Masson SAS on behalf of SERDI Publisher. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).