Fecal and urinary NMR-based metabolomics unveil an aging signature in mice

Exp Gerontol. 2014 Jan:49:5-11. doi: 10.1016/j.exger.2013.10.010. Epub 2013 Oct 29.

Abstract

Background: Aging is characterized by derangements in multiple metabolic pathways that progressively constrict the homeostatic reserve (homeostenosis). The signature of metabolic alterations that accompany aging can be retrieved through the metabolomic profiling of biological fluids.

Objective: To characterize the age-related changes in urinary and fecal metabolic profiles of BALB/c mice through a (1)H nuclear magnetic resonance (NMR)-based metabolomic approach.

Methods: Young (n=19) and old (n=13) male BALB/c mice were fed ad libitum standard laboratory chow. Twenty four-hour feces and urine were collected using metabolic cages and analyzed by high-resolution (1)H NMR spectroscopy combined with multivariate statistical analyses.

Results: An age-related metabolic phenotype was detected both in urine and feces. The metabolic signature of aging consisted of changes in levels of metabolites associated with amino acid metabolism, tricarboxylic acid cycle, tryptophan-nicotinamide adenine dinucleotide pathway, and host-microbiota metabolic axis.

Conclusions: Our (1)H NMR-based metabolomic approach was able to characterize the effect of age on urinary and fecal metabotypes. The implementation of this analytical strategy may increase our understanding of the metabolic alterations involved in the aging process and assist in the design of anti-aging interventions.

Keywords: (3-trimethylsilyl)propionic-(2,2,3,3-d4)-acid; 1-methylnicotinamide; 1MNA; AUROC; Area Under the ROC curve; DQ2; Discriminant Q2; LV; Latent Variable; MS; Metabolic footprint; Metabolic profiling; Metabolome; Methylnicotinamide; NMC; NMR; NNMT; Number of Misclassification; PBS; PLS-DA; Partial Least Squares-Discriminant Analysis; RP; Rank Product; S-adenosylmethionine; SAM; Senescence; TCA; THP; TSP; Tamm–Horsfall protein; VIP; mass spectrometry; nicotinamide N-methyltransferase; nuclear magnetic resonance; phosphate buffered saline; tricarboxyl acid cycle; variable importance in projection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Aging / urine
  • Animals
  • Biomarkers / metabolism
  • Biomarkers / urine
  • Feces / chemistry*
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Metabolic Networks and Pathways / physiology
  • Metabolome / physiology*
  • Metabolomics / methods
  • Mice
  • Mice, Inbred BALB C
  • Urinalysis / methods

Substances

  • Biomarkers