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The Aging Process: A Metabolomics Perspective.

Alex Castro1, Étore F Signini2, Juliana Magalhães De Oliveira1

  • 1Department of Chemistry, Universidade Federal de São Carlos, São Carlos 13565-905, Brazil.

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|December 23, 2022
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Summary
This summary is machine-generated.

Aging is linked to changes in serum metabolites, including decreased branched-chain amino acids and increased urea cycle metabolites after age 30. This study used metabolomics to identify these age-related metabolic shifts.

Keywords:
liquid chromatography-high-resolution mass spectrometrymetabolismmetabolomenuclear magnetic resonance

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Area of Science:

  • Gerontology and Metabolomics
  • Biochemistry and Aging Research

Background:

  • The aging process involves a decline in physiological functions, with underlying metabolic mechanisms not fully understood.
  • Metabolomics offers a powerful tool to identify biomarkers and elucidate age-regulated metabolic pathways.

Purpose of the Study:

  • To investigate age-related changes in serum metabolic profiles using a comprehensive metabolomics approach.
  • To identify specific metabolites and metabolic pathways associated with aging in healthy adults.

Main Methods:

  • Analysis of fasting serum samples from 138 healthy individuals (20-70 years) using Proton Nuclear Magnetic Resonance (1H NMR) and Liquid Chromatography-High-Resolution Mass Spectrometry (LC-HRMS).
  • Exploration of age-metabolite associations using correlation analysis, Metabolite Set Enrichment Analysis, Multiple Linear Regression, and Aging Metabolism Breakpoint analysis.

Main Results:

  • Age correlated positively with clinical markers (cholesterol, glucose) and negatively with branched-chain amino acids (valine, leucine, isoleucine) and tryptophan.
  • Age positively correlated with aspartate and ornithine, indicating altered urea cycle and ammonia recycling pathways.
  • Specific metabolites (3-hydroxyisobutyrate, isoleucine, aspartate, ornithine) explained 27.3% of age variation, with a metabolic breakpoint after the third decade.

Conclusions:

  • Aging is associated with reduced serum branched-chain amino acid levels, particularly after age 30.
  • Progressively increased serum metabolites related to the urea cycle are indicative of the aging process.
  • Metabolomics provides insights into age-related metabolic shifts, highlighting potential targets for understanding and intervening in aging.