1. Cell Biology
  2. Genetics and Genomics
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Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity

  1. Siming Ma
  2. Akhil Upneja
  3. Andrzej Galecki
  4. Yi-Miau Tsai
  5. Charles F Burant
  6. Sasha Raskind
  7. Quanwei Zhang
  8. Zhengdong D Zhang
  9. Andrei Seluanov
  10. Vera Gorbunova
  11. Clary B Clish
  12. Richard A Miller
  13. Vadim N Gladyshev  Is a corresponding author
  1. Brigham and Women's Hospital, Harvard Medical School, United States
  2. University of Michigan Medical School, United States
  3. Albert Einstein College of Medicine, United States
  4. University of Rochester, United States
  5. Broad Institute, United States
Research Article
  • Cited 37
  • Views 3,438
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Cite this article as: eLife 2016;5:e19130 doi: 10.7554/eLife.19130

Abstract

Mammalian lifespan differs by >100-fold, but the mechanisms associated with such longevity differences are not understood. Here, we conducted a study on primary skin fibroblasts isolated from 16 species of mammals and maintained under identical cell culture conditions. We developed a pipeline for obtaining species-specific ortholog sequences, profiled gene expression by RNA-seq and small molecules by metabolite profiling, and identified genes and metabolites correlating with species longevity. Cells from longer-lived species up-regulated genes involved in DNA repair and glucose metabolism, down-regulated proteolysis and protein transport, and showed high levels of amino acids but low levels of lysophosphatidylcholine and lysophosphatidylethanolamine. The amino acid patterns were recapitulated by further analyses of primate and bird fibroblasts. The study suggests that fibroblast profiling captures differences in longevity across mammals at the level of global gene expression and metabolite levels and reveals pathways that define these differences.

Article and author information

Author details

  1. Siming Ma

    Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Akhil Upneja

    Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Andrzej Galecki

    Department of Pathology, University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yi-Miau Tsai

    Department of Pathology, University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Charles F Burant

    Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Sasha Raskind

    Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Quanwei Zhang

    Department of Genetics, Albert Einstein College of Medicine, Bronx, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Zhengdong D Zhang

    Department of Genetics, Albert Einstein College of Medicine, Bronx, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Andrei Seluanov

    Department of Biology, University of Rochester, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Vera Gorbunova

    Department of Biology, University of Rochester, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Clary B Clish

    Broad Institute, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Richard A Miller

    Department of Pathology, University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Vadim N Gladyshev

    Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, United States
    For correspondence
    vgladyshev@rics.bwh.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0372-7016

Funding

NIH Office of the Director (AG047745)

  • Vadim N Gladyshev

National Institutes of Health (AG047200)

  • Zhengdong D Zhang
  • Andrei Seluanov
  • Vera Gorbunova
  • Vadim N Gladyshev

National Institutes of Health (AG023122)

  • Vadim N Gladyshev

National Institutes of Health (DK089503)

  • Vadim N Gladyshev

National Institutes of Health (DK097153)

  • Vadim N Gladyshev

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Amy J Wagers, Harvard University, United States

Publication history

  1. Received: June 26, 2016
  2. Accepted: November 21, 2016
  3. Accepted Manuscript published: November 22, 2016 (version 1)
  4. Version of Record published: December 9, 2016 (version 2)

Copyright

© 2016, Ma et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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