Biological Aging Exhibits an Inverted J-Shaped Relationship with Stress Urinary Incontinence in Women

BACKGROUND: Biological aging is a systemic driver of chronic disease, yet its relationship with female urinary incontinence (UI) remains unexamined. We leveraged three conceptually distinct metrics-PhenoAge (PA), Klemera-Doubal Method (KDM), and Homeostatic Dysregulation (HD)-to quantify biological age and assessed their associations with stress UI (SUI), urgency UI (UUI), and mixed UI (MUI) in a nationally representative cohort. METHODS: This cross-sectional study included 8,561 women ≥20 years from NHANES 2005-2010 and 2015-2018. After outlier exclusion and covariate selection via LASSO regression, multivariable logistic regression and restricted cubic splines (RCS) were used to estimate ORs and dose-response shapes. Subgroup analyses, mediation analyses, and sensitivity analyses were performed. RESULTS: PA and KDM were positively associated with UI. The third quartile of PA and KDM conferred the highest risk for SUI (PA: Q3 OR = 1.58, 95% CI 1.33-1.88; KDM: Q3 OR = 1.39, 95% CI 1.20-1.62). Higher quartiles were also linked to greater UI severity. Fully adjusted RCS models revealed inverted J-shaped relationships for SUI (PA inflection: 43.6; KDM: 34.7) and inverted U-shaped relationships for UUI and MUI with KDM (UUI inflections: 40.7 and MUI inflections: 40.5). Associations were robust across most subgroups but attenuated with increasing reproductive risk factors. No significant mediation by sex steroids or α-Klotho was observed. CONCLUSION: Biological aging is significantly positively associated with UI, and its relationship with SUI follows an inverted J-shaped curve. Interventions that slow biological aging may offer a novel strategy for UI prevention; however, longitudinal studies are required to establish causality.