Sex-stratified and ascorbic acid intake-modified associations between body roundness index and biological aging: a NHANES-based study on interactions and mediation.

Background: Biological aging, defined as the biological age (BA) or phenotypic age (PA) exceeding the chronological age (CA), is a key indicator of premature aging. Obesity accelerates aging; however, the effect of Body Roundness Index (BRI), an indicator of abdominal obesity, combined with sex or Ascorbic acid (Asc), on biological aging remains unclear. This study examined the association between BRI and biological aging, its interaction with sex and Asc intake, and its mediating mechanisms.

Methods: Data from the 1999-2018 U.S. National Health and Nutrition Examination Survey (NHANES) formed the basis of this study. Biological aging is characterized by BA or PA surpassing CA. Association between the BRI and biological aging was evaluated using multivariable-adjusted weighted regression. To assess for nonlinearity, restricted cubic splines were utilized, while interactions were investigated through both additive and multiplicative analyses. The bootstrap method was used to examine the potential mediating effects of biomarkers of metabolic dysfunction, oxidative stress, and protective pathways.

Results: The final analysis included 14,337 U.S. adults (mean age 47.5 years; 50.27% women). A total of 49.32% of the participants showed signs of biological aging, with BRI being positively associated with biological aging in a nonlinear manner, including a threshold effect. The increase in the risk per BRI unit was more significant in women, and high doses of Asc reduced the risk of biological aging associated with increased BRI. Mediation analysis indicated that the association between BRI and accelerated aging was partly mediated by metabolic dysfunction (mediated by the triglyceride-glucose index [18.73%] and by triglycerides [9.21%], oxidative stress mediated by uric acid [17.92%] and by white blood cell count [5.80%], and depletion of protective factors mediated by vitamin D [- 3.85%] and by high-density lipoprotein [- 4.24%]). A sensitivity analysis confirmed the reliability of the findings.

Conclusions: A higher BRI showed a nonlinear positive association with accelerated biological aging, a relationship that appears to be modified by female sex and Asc intake. Clinical approaches targeting metabolic dysfunction, oxidative stress, and antioxidant and vasoprotective reserves may help combat obesity-related aging. BRI thresholds enable early identification of individuals at high risk for personalized interventions.