1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast

  1. Sara N Mouton
  2. David J Thaller
  3. Matthew M Crane
  4. Irina L Rempel
  5. Owen T Terpstra
  6. Anton Steen
  7. Matt Kaeberlein
  8. C Patrick Lusk
  9. Arnold J Boersma  Is a corresponding author
  10. Liesbeth M Veenhoff  Is a corresponding author
  1. University of Groningen, Netherlands
  2. Yale School of Medicine, United States
  3. University of Washington, United States
  4. DWI-Leibniz Institute for Interactive Materials, Germany
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Cite this article as: eLife 2020;9:e54707 doi: 10.7554/eLife.54707

Abstract

Cellular aging is a multifactorial process that is characterized by a decline in homeostatic capacity, best described at the molecular level. Physicochemical properties such as pH and macromolecular crowding are essential to all molecular processes in cells and require maintenance. Whether a drift in physicochemical properties contributes to the overall decline of homeostasis in aging is not known. Here we show that the cytosol of yeast cells acidifies modestly in early aging and sharply after senescence. Using a macromolecular crowding sensor optimized for long-term FRET measurements, we show that crowding is rather stable and that the stability of crowding is a stronger predictor for lifespan than the absolute crowding levels. Additionally, in aged cells we observe drastic changes in organellar volume, leading to crowding on the µm scale, which we term organellar crowding. Our measurements provide an initial framework of physicochemical parameters of replicatively aged yeast cells.

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Author details

  1. Sara N Mouton

    European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9429-3788

  2. David J Thaller

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3577-5562

  3. Matthew M Crane

    Department of Pathology, School of Medicine, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6234-0954

  4. Irina L Rempel

    European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.

  5. Owen T Terpstra

    European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.

  6. Anton Steen

    European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
    Competing interests
    No competing interests declared.

  7. Matt Kaeberlein

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    Matt Kaeberlein, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1311-3421

  8. C Patrick Lusk

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4703-0533

  9. Arnold J Boersma

    DWI-Leibniz Institute for Interactive Materials, DWI-Leibniz Institute for Interactive Materials, Aachen, Germany
    For correspondence
    boersma@dwi.rwth-aachen.de
    Competing interests
    No competing interests declared.

  10. Liesbeth M Veenhoff

    European Research Institute for the Biology of Ageing, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
    For correspondence
    l.m.veenhoff@rug.nl
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0158-4728

Funding

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (737.016.016)

  • Liesbeth M Veenhoff

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (723.015.002)

  • Arnold J Boersma

National Institutes of Health (RO1 GM105672)

  • C Patrick Lusk

National Institutes of Health (P30 AG013280)

  • Matt Kaeberlein

National Institutes of Health (R01 AG056359)

  • Matt Kaeberlein

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

Reviewing Editor

  1. Weiwei Dang, Baylor College of Medicine, United States

Publication history

  1. Received: December 23, 2019
  2. Accepted: September 28, 2020
  3. Accepted Manuscript published: September 29, 2020 (version 1)
  4. Version of Record published: October 14, 2020 (version 2)

Copyright

© 2020, Mouton 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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