Abstract

A comprehensive description of the phenotypic changes during cellular aging is key towards unraveling its causal forces. Previously, we mapped age-related changes in the proteome and transcriptome changes (Janssens et al., 2015). Here, we use these results and model-based inference to generate a comprehensive account of metabolic changes during the replicative life of Saccharomyces cerevisiae. With age, we found decreasing metabolite levels, decreasing growth and substrate uptake rates accompanied by a switch from aerobic fermentation to respiration, with glycerol and acetate production. The identified metabolic fluxes revealed an increase in redox cofactor turnover, likely to combat increased production of reactive oxygen species. The metabolic changes are possibly a result of the age-associated decrease in surface area per cell volume. With metabolism being an important factor of the cellular phenotype, this work complements our recent mapping of the transcriptomic and proteomic changes towards a holistic description of the cellular processes during aging.

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All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Simeon Leupold

    Molecular Systems Biology, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7186-7061
  2. Georg Hubmann

    Molecular Systems Biology, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Athanasios Litsios

    Molecular Systems Biology, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3588-4988
  4. Anne C Meinema

    Molecular Systems Biology, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0002-3486
  5. Vakil Takhaveev

    Molecular Systems Biology, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Alexandros Papagiannakis

    Molecular Systems Biology, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Bastian Niebel

    Molecular Systems Biology, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  8. Georges Janssens

    European Research Institute for the Biology of Ageing, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  9. David Siegel

    Analytical Biochemistry, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  10. Matthias Heinemann

    Molecular Systems Biology, University of Groningen, Groningen, Netherlands
    For correspondence
    m.heinemann@rug.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5512-9077

Funding

Nederlandse Organisatie voor Wetenschappelijk Onderzoek

  • Matthias Heinemann

European Commission (642738)

  • Vakil Takhaveev
  • Matthias Heinemann

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

Reviewing Editor

  1. Karsten Weis, ETH Zurich, Switzerland

Version history

  1. Received: August 29, 2018
  2. Accepted: April 9, 2019
  3. Accepted Manuscript published: April 9, 2019 (version 1)
  4. Version of Record published: April 16, 2019 (version 2)

Copyright

© 2019, Leupold 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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  1. Simeon Leupold
  2. Georg Hubmann
  3. Athanasios Litsios
  4. Anne C Meinema
  5. Vakil Takhaveev
  6. Alexandros Papagiannakis
  7. Bastian Niebel
  8. Georges Janssens
  9. David Siegel
  10. Matthias Heinemann
(2019)
Saccharomyces cerevisiae goes through distinct metabolic phases during its replicative lifespan
eLife 8:e41046.
https://doi.org/10.7554/eLife.41046

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https://doi.org/10.7554/eLife.41046

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