Accelerated Biological Aging and a Nonlinear Risk Threshold for Sleep Apnea: Evidence from NHANES and Mediation by Oxidative-Metabolic Dysregulation

Abstract Background The association between accelerated biological aging and sleep apnea remains unclear. This study aimed to investigate the association of phenotypic aging (PhenoAge) with sleep apnea, identify nonlinear patterns and high-risk subgroups, and explore metabolic-oxidative stress (as measured by uric acid-to-HDL ratio, UHR) as a potential mediator. Methods In a cross-sectional analysis of 4,901 adults from NHANES 2005–2008, sleep apnea was self-reported. PhenoAge was calculated from clinical biomarkers. Associations were assessed using multivariable logistic regression and restricted cubic splines; potential mediation by UHR was evaluated. Results Each 1-year increase in PhenoAge was associated with a 3% higher odds of sleep apnea (OR=1.03, 95% CI: 1.01–1.04). A statistically derived nonlinear inflection point at a PhenoAge of 44.09 years was observed. The association was significant only in adults ≥40 years ( P -interaction=0.001) and was strongest in males and individuals with obesity. UHR accounted for 6.27% of the association, primarily in adults ≥40 years and individuals with obesity. Conclusion In this cross-sectional study, accelerated biological aging, measured by PhenoAge, was associated with sleep apnea in a dose-dependent and age-delimited manner, with a statistical inflection point at 44.09 years. The modest association via UHR suggests oxidative-metabolic dysregulation as one potential explanatory factor. These exploratory findings provide a framework for hypothesis generation regarding the role of biological aging in sleep apnea.