Age-and diet-associated metabolome remodeling characterizes the aging process driven by damage accumulation

Andrei S. Avanesov, Siming Ma, Kerry A. Pierce, Sun Hee Yim, Byung Cheon Lee, Clary B. Clish, Vadim N. Gladyshev

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Aging is thought to be associated with increased molecular damage, but representative markers vary across conditions and organisms, making it difficult to assess properties of cumulative damage throughout lifespan. We used nontargeted metabolite profiling to follow age-associated trajectories of >15,000 metabolites in Drosophila subjected to control and lifespan-extending diets. We find that aging is associated with increased metabolite diversity and low-abundance molecules, suggesting they include cumulative damage. Remarkably, the number of detected compounds leveled-off in late-life, and this pattern associated with survivorship. Fourteen percent of metabolites showed age-associated changes, which decelerated in late-life and long-lived flies. In contrast, known metabolites changed in abundance similarly to nontargeted metabolites and transcripts, but did not increase in diversity. Targeted profiling also revealed slower metabolism and accumulation of lifespan-limiting molecules. Thus, aging is characterized by gradual metabolome remodeling, and condition-and advanced age-associated deceleration of this remodeling is linked to mortality and molecular damage.

Original languageEnglish
Article numbere02077
JournaleLife
Volume2014
Issue number3
DOIs
Publication statusPublished - 2014 Apr 29
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Avanesov, A. S., Ma, S., Pierce, K. A., Yim, S. H., Lee, B. C., Clish, C. B., & Gladyshev, V. N. (2014). Age-and diet-associated metabolome remodeling characterizes the aging process driven by damage accumulation. eLife, 2014(3), [e02077]. https://doi.org/10.7554/eLife.02077.001