Plasma Taurine Relative Abundance, Not Dietary Intake or Genetic Predisposition, Predicts All-Cause Mortality and Unhealthy Ageing: A Prospective Cohort Study

Abstract Background: The influence of taurine on biological ageing remains unclear, particularly whether it acts as a causal driver or a functional biomarker. We aimed to disentangle the distinct roles of plasma taurine relative abundance, dietary taurine supply, and genetic metabolic capacity on all-cause mortality and unhealthy ageing. Methods: This prospective study used data from the Korean Genome and Epidemiology Study (2001~2022). A subcohort of 2,321 participants (mean age 56.5 years; 51.4% female) with complete metabolomic, dietary, and genomic data was analyzed. Three independent pathways were evaluated: (1) plasma taurine/total amino acid (AA) ratio, (2) dietary taurine to protein ratio, and (3) a weighted genetic risk score (GRS) from 21 SNPs in taurine biosynthesis and transport genes. Primary outcomes were all-cause mortality and unhealthy ageing (Physiological Healthy Ageing Index [PHAI] score [≤] 25th percentile). Results: A higher plasma taurine/total AA ratio was consistently associated with improved ageing outcomes. Participants in the highest quartile showed 29% lower all-cause mortality (Hazard Ratio [HR], 0.71; 95% Confidence Interval [CI], 0.52-0.98; P for trend = .04) and lower risk of PHAI-based unhealthy ageing (HR, 0.77; 95% CI, 0.59-1.00; P for trend = .04) versus the lowest quartile. Dietary taurine-to-protein ratio was not associated with mortality (P for trend = .70), nor was the GRS (P for trend = .74). Conclusions: The protective association of taurine was linked to its relative abundance within the systemic amino acid pool, rather than dietary intake or genetic predisposition, supporting taurine as a functional biomarker of metabolic efficiency rather than a deterministic causal driver of ageing.