A recent study suggests that circulating glucuronic acid may be a useful predictor of both lifespan and healthspan in humans and mice.
What is glucuronic acid?
Glucuronic acid is a metabolite of glucose and is critical for the detoxification of xenobiotic substances. These are compounds that are not naturally produced, should not normally be in the body, or are present in higher concentrations than normal.
Xenobiotic compounds include molecules from drugs, hormones ingested from food sources, and pollutants, and glucuronidation is the body’s way of dealing with these problem compounds and removing them. This process involves the modification of unwanted compounds by the addition of glucuronic acid, which makes them more soluble to bile, allowing it to be broken down easier and excreted in the urine.
However, an enzyme known as β-glucuronidase is known to interfere with the process by preventing the modification of the xenobiotic compounds, which stops this detoxification process from working. Many bacteria present in the gut produce β-glucuronidases, and they are directly associated with the increased risk of xenobiotic-induced toxicity.
Another important function of glucuronic acid is to support the formation of proteoglycans, a family of proteins that are components of the extracellular matrix. The proteoglycans are broken down by the β-glucuronidase in our own lysosomes, which facilitates tissue remodelling as part of normal function.
Glucuronic acid as a potential aging biomarker
The study shows that glucuronic acid levels typically rise during aging and suggests that this directly correlates with longevity and lifespan . The researchers examined the presence of glucuronic acid by looking at three human studies and a mouse study, and they suggest that levels of glucuronic acid circulating in the bloodstream are a robust predictor of all-cause mortality, age, and healthspan.
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.
Why does this happen? It may be due to changes to the gut microbiome that lead to an overproduction of glucuronic acid and a reduction of the ability to remove xenobiotic substances. The exact mechanisms at play that maintain the balance between glucuronic acid and β-glucuronidase are not fully understood, so more research is certainly needed here.
That said, there is an urgent need for more aging biomarkers in order to ascertain the effectiveness of therapies designed to delay, halt, or reverse aging. Such biomarkers could then be used as part of a panel to provide robust confirmation that any given approach works or not. Glucuronic acid could turn out to be a useful biomarker for this purpose, and, given the ease with which blood samples can be examined, could be a cost-effective one.
 Ho, A., Sinick, J., Esko, T., Fischer, K., Menni, C., Zierer, J., … & Morgen, E. K. (2019). Circulating glucuronic acid predicts healthspan and longevity in humans and mice. Aging, 11.