Frailty phenotype reveals heterogeneity in aging and distinct taurine associations

Frailty, characterized by diminished physiological reserve and increased vulnerability to stressors, is a common geriatric syndrome associated with adverse health outcomes. While recent seminal studies have reported conflicting findings regarding taurine, a sulfur-containing amino acid with antioxidant properties, and its relationship with aging, these discrepancies may reflect the heterogeneity of aging trajectories among older adults that chronological age alone fails to capture. Here, we propose that frailty status may better capture this heterogeneity and reveal associations between taurine and aging that are obscured when using age alone. We examined taurine and upstream metabolites in the taurine biosynthesis pathway in 146 community-dwelling adults aged 20-97 years, focusing on older adults (≥69 years) stratified by frailty phenotype. We observed a non-monotonic relationship where taurine levels were highest in robust individuals, lowest in prefrail, and intermediate in frail groups. Analysis of the taurine biosynthesis pathway revealed distinct metabolic profiles across frailty states. Robust individuals demonstrated efficient pathway flux, while the prefrail group exhibited maximal metabolic disruption characterized by bottlenecks. Frail individuals showed persistent metabolic disruption but partial taurine restoration, suggesting compensatory mechanisms. Inflammatory marker associations varied by frailty status, with TNF-α showing a significant negative correlation with taurine specifically in prefrail individuals. These findings demonstrate that frailty status reveals distinct shifts in taurine metabolism and immunological regulation not captured by chronological age alone, providing a more biologically meaningful framework for understanding taurine biology in aging populations.