Circulating glucuronic acid predicts healthspan and longevity in humans and mice

Glucuronic acid is a metabolite of glucose that is involved in the detoxification of xenobiotic compounds and the structure/remodeling of the extracellular matrix. We report for the first time that circulating glucuronic acid is a robust biomarker of mortality that is conserved across species. We find that glucuronic acid levels are significant predictors of all-cause mortality in three population-based cohorts from different countries with 4-20 years of follow-up (HR=1.44, p=2.9×10^-6 in the discovery cohort; HR=1.13, p=0.032 and HR=1.25, p=0.017, respectively in the replication cohorts), as well as in a longitudinal study of genetically heterogenous mice (HR=1.29, p=0.018). Additionally, we find that glucuronic acid levels increase with age and predict future healthspan-related outcomes. Together, these results demonstrate glucuronic acid as a robust biomarker of longevity and healthspan.