Joint association of serum 25-hydroxyvitamin D concentration and body mass index on the acceleration of clinical biomarker-based biological aging

Background The possible joint association of vitamin D and obesity in regard to the clinical biomarker-based biological aging process has not been well studied. We aimed to investigate the independent and combined associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations and body mass index (BMI) with phenotypic age (PhenoAge) and Klemera-Doubal method Biological Age (KDM-BA) acceleration. Methods This study was conducted using data from participants in the UK Biobank baseline survey. PhenoAge and KDM-BA acceleration were calculated as the residuals from regressing PhenoAge and KDM-BA on chronological age. Restricted cubic splines and multivariable logistic regression analyses were used to investigate the associations of serum 25(OH)D concentrations and BMI with PhenoAge and KDM-BA acceleration. Interaction terms were introduced to evaluate whether the combined effects of the two factors exceeded their cumulative effects. Mediation analyses were conducted to assess whether PhenoAge or KDM-BA acceleration potentially mediated the association between 25(OH)D or BMI and all-cause mortality. Results In both Analysis 1 (n = 389,217) for PhenoAge, and Analysis 2 for KDM-BA (n = 329,561), participants had similar mean ages (56.49 ± 8.12 and 56.34 ± 8.13 years), sex distributions (46.7% and 46.5% men), and predominantly White ethnicity (95.0%). Consistent relationships were found between 25(OH)D, BMI and clinical biomarker-based biological age acceleration measured by PhenoAge and KDM-BA. Participants whose serum 25(OH)D concentration ≥ 50.0 nmol/L or with normal weight (BMI < 25kg/m2) had the lowest odds of clinical biomarker-based biological age acceleration. Compared to participants with serum 25(OH)D levels ≥ 50.0 nmol/L and the normal weight, participants with both 25(OH)D < 25.0 nmol/L and BMI ≥ 30.0 kg/m2 had the highest odds of PhenoAge acceleration [OR (95% CI), 2.387 (2.303, 2.474)] and KDM-BA acceleration [OR (95% CI), 4.096 (3.926, 4.274)]. The mediation analysis revealed that PhenoAge acceleration mediated 11.4% and 47.1% of the associations of 25(OH)D and BMI with all-cause mortality, while KDM-BA acceleration accounted for 7.41% and 55.2% of these associations. Conclusions Serum 25(OH)D concentrations and BMI were significantly associated with the acceleration of biological aging. Combining vitamin D deficiency and obesity demonstrated enhanced synergistic association on the biological aging process, highlighting the importance of vitamin D and BMI in promoting healthy aging.