Joint association of eGDR and long-term maintenance of healthy BMI range with light BioAge acceleration

Biological aging trajectories vary considerably among individuals of the same chronological age, partly attributable to differences in metabolic health. Nevertheless, the combined influence of long-term weight maintenance and insulin resistance on Light BioAge acceleration remains insufficiently characterized. Data were derived from two population-based cohorts: the China Health and Retirement Longitudinal Study (CHARLS) and the UK Biobank. Time in target range for body mass index (TTR-BMI) was used to characterize long-term BMI stability, while insulin sensitivity was assessed using the estimated glucose disposal rate (eGDR). Biological age was estimated using the Light BioAge model, which incorporates chronological age, serum creatinine, fasting glucose, and C-reactive protein. Multivariable logistic regression, restricted cubic spline analyses, joint analyses of TTR-BMI and eGDR, and exploratory mediation analyses were performed. The analysis included 7,962 CHARLS participants and 11,142 UK Biobank participants. Higher TTR-BMI was consistently associated with lower odds of accelerated aging in both cohorts. Compared with individuals who remained within the healthy BMI range, those with never or partial time within the target range showed higher odds of accelerated aging. Similarly, higher eGDR levels, indicating better insulin sensitivity, were associated with lower odds of accelerated aging. Exploratory mediation analyses yielded estimated proportions mediated by eGDR of 83.9% in CHARLS and 81.4% in the UK Biobank; however, the concurrent assessment of eGDR and biological age precluded establishing a temporal mediation sequence. Long-term BMI trajectories within the healthy range and higher eGDR levels were associated with lower odds of accelerated aging in two independent cohorts. Residual confounding, reverse causation, and selection into repeated assessments limit causal interpretation, and the exploratory mediation findings do not establish a pathway through insulin sensitivity.