Circulating PBX1 and age-related sarcopenia phenotypes: metabolic mediation analyses in a community-based study.

To determine whether circulating PBX1 is associated with AWGS2019-defined sarcopenia phenotypes in older adults, and whether alanine-related metabolites mediate the PBX1-ASMI association. We enrolled 324 adults aged 60 years or older from Licha Town, Qingdao, China (2022-2023) and classified sarcopenia using AWGS 2019. Plasma PBX1 was quantified by ELISA, and targeted plasma metabolite profiling was performed by LC-MS/MS. Primary outcomes were appendicular skeletal muscle mass index (ASMI), 6-m gait speed, and maximal handgrip strength. Independent associations were estimated using multivariable linear regression. Mediation models quantified indirect statistical components of the PBX1-ASMI association through prespecified metabolites (alanine and the lactic acid/alanine ratio) with bootstrap confidence intervals. ROC analyses assessed discrimination for sarcopenia and severe sarcopenia. Higher plasma PBX1 was independently associated with greater ASMI, faster gait speed, and stronger handgrip strength (all P < 0.001). PBX1 was positively associated with alanine and inversely associated with the lactic acid/alanine ratio. Alanine and the lactic acid/alanine ratio accounted for 10.79% (P = 0.017) and 10.11% (P = 0.002) of the PBX1-ASMI association, respectively; indirect components for gait speed and handgrip strength were not statistically significant. PBX1 discriminated sarcopenia (AUC 0.748) and severe sarcopenia (AUC 0.771), with high negative predictive value for severe sarcopenia at Youden-optimal thresholds. Circulating PBX1 is independently associated with preserved muscle mass and function in older adults. PBX1 warrants external validation and longitudinal evaluation as a clinically informative correlate and candidate adjunctive biomarker for sarcopenia risk stratification.