Microbial–Mammalian Cometabolites Dominate the Age-associated Urinary Metabolic Phenotype in Taiwanese and American Populations

Abstract

Understanding the metabolic processes associated with aging is key to developing effective management and treatment strategies for age-related diseases. We investigated the metabolic profiles associated with age in a Taiwanese and an American population. 1H NMR spectral profiles were generated for urine specimens collected from the Taiwanese Social Environment and Biomarkers of Aging Study (SEBAS; n= 857; age 54-91 years) and the Mid-Life in the USA study (MIDUS II; n= 1148; age 35-86 years). Multivariate and univariate linear projection methods revealed some common age-related characteristics in urinary metabolite profiles in the American and Taiwanese populations, as well as some distinctive features. In both cases, two metabolites--4- cresyl sulfate (4CS) and phenylacetylglutamine (PAG)—were positively associated with age. In addition, creatine and β-hydroxy-β-methylbutyrate (HMB) were negatively correlated with age in both populations (p<4×10-6). These age-associated gradients in creatine and HMB reflect decreasing muscle mass with age. The systematic increase in PAG and 4CS was confirmed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Both are products of concerted microbial-mammalian host co-metabolism and indicate an age-related association with the balance of host-microbiome metabolism.