Abstract
OBJECTIVE: This study aims to explore the association of BRI with all-cause, cardiovascular disease (CVD)-cause, and cancer-cause mortality risk, and the role of biological age acceleration (BAA) in mediating these associations. METHODS: We included 305,406 participants in the UK biobank. BRI was calculated based on waist circumference (WC) and height. BAA was divided into klemera-doubal method biological age acceleration (KDM-BA) and PhenoAge acceleration. The associations of BRI, BAA with outcomes were assessed by Cox proportional hazard models. The role of BAA in this association was analyzed by mediating effect. RESULTS: Compared with the individuals with the lowest BRI quartile, the individuals with the highest BRI quartile had a higher hazard of death, and the HR and 95% CI of all-cause death, CVD death and cancer death were (HR: 1.43 (95% CI: 1.33, 1.53)), (HR: 1.47 (95% CI: 1.25, 1.72)), (HR: 1.38 (95% CI: 1.26, 1.52)), respectively. The mediation proportion of BAA in associations of BRI with death outcomes were 10.75–42.98% (all p < 0.001). CONCLUSION: BRI is associated with an increased hazard of all-cause death, CVD death, and cancer death, BAA partially mediated these associations. We observed that higher levels of BRI were associated with an increased hazard of death, with biological age acceleration potentially mediating this association. This suggests that maintaining a healthy lifestyle and reducing the inflammatory/immune response and lipid metabolism abnormalities associated with obesity are critical to reducing the burden of chronic disease. The future intervention targets will be maintaining WC at appropriate levels that might contribute to self-health management. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12937-025-01209-2.