A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast
- University of Groningen, Netherlands
- Yale School of Medicine, United States
- University of Washington, United States
- DWI-Leibniz Institute for Interactive Materials, Germany
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1,2,3,4.
Article and author information
Author details
Liesbeth M Veenhoff
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
- Weiwei Dang, Baylor College of Medicine, United States
Version history
- Received: December 23, 2019
- Accepted: September 28, 2020
- Accepted Manuscript published: September 29, 2020 (version 1)
- 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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A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast
eLife 9:e54707.
https://doi.org/10.7554/eLife.54707
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