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.

NMR-Based Metabolomic Profiling of Overweight Adolescents: An Elucidation of the Effects of Inter-/Intraindividual Differences, Gender, and Pubertal Development

“…Gu et al [9] reported that urinary hippurate excretion may vary less during childhood development, although a relatively large variation in hippurate with age was found for adults by Psihogios et al [37]. In addition, the data reported by Swann et al [52] indicated that urinary phenylacetylglutamine concentrations were increased with age in adults. Urinary hippurate and phenylacetylglutamine have often been related to the activity of the gut microflora [53], so our results suggest that the gut microflora may vary with Tanner stage.…”

Emerging Insights into the Metabolic Alterations in Aging Using Metabolomics

“…Numerous metabolomics studies have explored age-related changes in metabolites levels and found that the metabolic profiles are strongly correlated with chronological age and/or longevity (Table 1) [56,59,94,[109][110][111][112][113][114][115]. For example, Lawton et al characterized the effect of age and sex on human plasma metabolome from a cohort of 269 individuals while using untargeted metabolomics, and found that more than 100 metabolites were significantly altered with age, whereas relatively few metabolites were altered with either sex or race [115].…”

“…This study further revealed that the longevity process alters the structure and composition of human gut microbiota, such that the levels of phenylacetylglutamine (PAG) and p-cresol sulfate (PCS) are higher in the urine of centenarians, which indicates that a complex remodeling of lipids, amino acids, and gut microbiota metabolism mark the longevity in humans [94]. Another study investigated the urinary metabolic profiles with age of a Taiwanese and an American population, and reported that PAG and PCS metabolites are both positively correlated with age, suggesting an age-related association of the host-microbiome metabolism [112]. The authors further found that the levels of creatine and β-hydroxy-β-methylbutyrate (HMB) metabolites are negatively correlated with age in both populations, which indicates reduced muscle mass with age [112].…”

Urinary Metabolomics Profiles Associated to Bovine Meat Ingestion in Humans

“…All these compounds are present in meat and excreted in urine resulting in higher urinary concentrations under a meat‐containing diet. Most of them, except 1‐MH are also synthesized in the human body and may present important variations according to the sex and age, and their excretion may depend on dietary factors other than meat consumption.…”