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

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.