Research Paper|Volume 11, Issue 18|pp 7694—7706

Circulating glucuronic acid predicts healthspan and longevity in humans and mice

Andrew Ho¹, Jonah Sinick¹, Tõnu Esko², Krista Fischer^2,³, Cristina Menni⁴, Jonas Zierer⁴, Maria Matey-Hernandez⁴, Kristen Fortney¹, Eric K. Morgen¹

¹BIOAGE, Richmond, CA 94804, USA
²Estonian Genome Center, University of Tartu, Tartu 51010, Estonia
³Institute of Mathematics and Statistics, University of Tartu, Tartu 50409, Estonia
⁴Department of Twin Research, Kings College London, London SE1 7EH, United Kingdom

Received: August 7, 2019Accepted: September 7, 2019Published: September 26, 2019

https://doi.org/10.18632/aging.102281

Copyright © 2019 Ho et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.