Identifying sex-specific biomarkers for intrinsic capacity decline in the aging population

BACKGROUND: Intrinsic capacity (IC) decline is a key marker of aging-related functional loss, yet sex-specific biomarkers remain poorly characterized. This cross-sectional study of 1014 community-dwelling older adults investigated the associative strength and potential statistical intermediaries of insulin-like growth factor binding protein 2 (IGFBP2) and growth differentiation factor 15 (GDF-15) in IC impairment, with sex-stratified analyses. RESEARCH DESIGN AND METHODS: Dose-response relationships were assessed using restricted cubic splines. Multivariable logistic regression evaluated independent associations after adjusting for covariates. Mediation analysis explored roles of renal, muscular, metabolic, and oxidative stress indicators. RESULTS: IC impairment was associated with higher IGFBP2 and GDF-15 (all p < 0.001). In males, IGFBP2 showed a reverse L-shaped association (inflection at 310 ng/mL; AUC = 0.75), partially explained by renal function (β2-MG), muscle damage (CK, LDH), oxidative stress (SOD), and nutrition (ALB), with 11.02% mediation. In females, GDF-15 had a nonlinear relationship (inflection at 1.99 ng/mL; AUC = 0.76), attributable in part to glucose (FBG), lipids (FFA), and renal function (BUN), accounting for 19.8% of the effect. Fully adjusted ORs were 2.41 (IGFBP2 in males) and 4.27 (GDF-15 in females), both p < 0.001. CONCLUSION: IGFBP2 and GDF-15 are sex-specific biomarkers for IC decline, operating through distinct pathways, and may aid early screening and targeted interventions.