Effects of age, sex, and genotype on high-sensitivity metabolomic profiles in the fruit fly, Drosophila melanogaster

Authors

  • Jessica M. Hoffman,

    1. Department of Genetics, University of Georgia, Athens, GA, USA
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    • Co-first authors.
  • Quinlyn A. Soltow,

    1. Division of Pulmonary Allergy & Critical Care Medicine, Department of Medicine, Emory University, Atlanta, GA, USA
    2. Department of Medicine, Clinical Biomarkers Laboratory, Emory University, Atlanta, GA, USA
    3. ClinMet Inc., San Diego, CA, USA
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    • Co-first authors.
  • Shuzhao Li,

    1. Division of Pulmonary Allergy & Critical Care Medicine, Department of Medicine, Emory University, Atlanta, GA, USA
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  • Alfire Sidik,

    1. Department of Genetics, University of Georgia, Athens, GA, USA
    Current affiliation:
    1. Department of Molecular Biosciences, University of Texas, Austin, TX, USA
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  • Dean P. Jones,

    1. Division of Pulmonary Allergy & Critical Care Medicine, Department of Medicine, Emory University, Atlanta, GA, USA
    2. Department of Medicine, Clinical Biomarkers Laboratory, Emory University, Atlanta, GA, USA
    3. Center for Health Discovery & Well Being, Emory University, Atlanta, GA, USA
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    • Co-senior authors.
  • Daniel E. L. Promislow

    Corresponding author
    1. Department of Genetics, University of Georgia, Athens, GA, USA
    Current affiliation:
    1. Department of Pathology and Department of Biology, University of Washington, Seattle, WA, USA
    • Correspondence

      Daniel Promislow, Department of Pathology and Department of Biology, University of Washington, Box 357705, 1959 NE Pacific Street, Seattle, WA 98195, USA. Tel.: +206 616 6994; fax: +206 616 8271; e-mail: promislo@uw.edu

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Summary

Researchers have used whole-genome sequencing and gene expression profiling to identify genes associated with age, in the hope of understanding the underlying mechanisms of senescence. But there is a substantial gap from variation in gene sequences and expression levels to variation in age or life expectancy. In an attempt to bridge this gap, here we describe the effects of age, sex, genotype, and their interactions on high-sensitivity metabolomic profiles in the fruit fly, Drosophila melanogaster. Among the 6800 features analyzed, we found that over one-quarter of all metabolites were significantly associated with age, sex, genotype, or their interactions, and multivariate analysis shows that individual metabolomic profiles are highly predictive of these traits. Using a metabolomic equivalent of gene set enrichment analysis, we identified numerous metabolic pathways that were enriched among metabolites associated with age, sex, and genotype, including pathways involving sugar and glycerophospholipid metabolism, neurotransmitters, amino acids, and the carnitine shuttle. Our results suggest that high-sensitivity metabolomic studies have excellent potential not only to reveal mechanisms that lead to senescence, but also to help us understand differences in patterns of aging among genotypes and between males and females.

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