Microbial-mammalian cometabolites dominate the age-associated urinary metabolic phenotype in Taiwanese and American populations

J Proteome Res. 2013 Jul 5;12(7):3166-80. doi: 10.1021/pr4000152. Epub 2013 Jun 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / pathology
  • Aging / urine*
  • Cresols / metabolism*
  • Glutamine / analogs & derivatives*
  • Glutamine / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Metabolome*
  • Middle Aged
  • Sex Characteristics
  • Sulfuric Acid Esters / metabolism*
  • Taiwan
  • United States


  • Cresols
  • Sulfuric Acid Esters
  • Glutamine
  • 4-cresol sulfate
  • phenylacetylglutamine