title: 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 ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). Both are products of concerted microbial-mammalian host cometabolism and indicate an age-related association with the balance of host-microbiome metabolism.
authors.affiliation: Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, Reading RG6 6AP, United Kingdom.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Swann
authors.forename: Konstantina
authors.initials: K
authors.lastname: Spagou
authors.forename: Matthew
authors.initials: M
authors.lastname: Lewis
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.forename: Dana A
authors.initials: DA
authors.lastname: Glei
authors.forename: Teresa E
authors.initials: TE
authors.lastname: Seeman
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Coe
authors.forename: Noreen
authors.initials: N
authors.lastname: Goldman
authors.forename: Carol D
authors.initials: CD
authors.lastname: Ryff
authors.forename: Maxine
authors.initials: M
authors.lastname: Weinstein
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
mesh_terms: D000368:Aged; D000375:Aging / Q000473:pathology / Q000652:urine*; D003408:Cresols / Q000378:metabolism*; D005973:Glutamine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D012727:Sex Characteristics; D013463:Sulfuric Acid Esters / Q000378:metabolism*; D013624:Taiwan; D014481:United States
chemical_list: D003408:Cresols; D013463:Sulfuric Acid Esters; D005973:Glutamine; C408690:4-cresol sulfate; C003089:phenylacetylglutamine