A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast

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 i...

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Main Authors: Sara N Mouton, David J Thaller, Matthew M Crane, Irina L Rempel, Owen T Terpstra, Anton Steen, Matt Kaeberlein, C Patrick Lusk, Arnold J Boersma, Liesbeth M Veenhoff
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2020-09-01
Series:eLife
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Online Access:https://elifesciences.org/articles/54707
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author Sara N Mouton
David J Thaller
Matthew M Crane
Irina L Rempel
Owen T Terpstra
Anton Steen
Matt Kaeberlein
C Patrick Lusk
Arnold J Boersma
Liesbeth M Veenhoff
author_facet Sara N Mouton
David J Thaller
Matthew M Crane
Irina L Rempel
Owen T Terpstra
Anton Steen
Matt Kaeberlein
C Patrick Lusk
Arnold J Boersma
Liesbeth M Veenhoff
author_sort Sara N Mouton
collection DOAJ
description 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 micrometer scale, which we term organellar crowding. Our measurements provide an initial framework of physicochemical parameters of replicatively aged yeast cells.
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spelling doaj.art-1b80c526f8be4038a0f0386d26ecaf5c2022-12-22T03:51:18ZengeLife Sciences Publications LtdeLife2050-084X2020-09-01910.7554/eLife.54707A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeastSara N Mouton0https://orcid.org/0000-0001-9429-3788David J Thaller1https://orcid.org/0000-0003-3577-5562Matthew M Crane2https://orcid.org/0000-0002-6234-0954Irina L Rempel3https://orcid.org/0000-0003-4655-5311Owen T Terpstra4https://orcid.org/0000-0002-8767-4061Anton Steen5https://orcid.org/0000-0002-1064-6038Matt Kaeberlein6https://orcid.org/0000-0002-1311-3421C Patrick Lusk7https://orcid.org/0000-0003-4703-0533Arnold J Boersma8https://orcid.org/0000-0002-3714-5938Liesbeth M Veenhoff9https://orcid.org/0000-0002-0158-4728European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Cell Biology, Yale School of Medicine, New Haven, United StatesDepartment of Pathology, School of Medicine, University of Washington, Seattle, United StatesEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsDepartment of Pathology, School of Medicine, University of Washington, Seattle, United StatesDepartment of Cell Biology, Yale School of Medicine, New Haven, United StatesDWI-Leibniz Institute for Interactive Materials, Aachen, GermanyEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, NetherlandsCellular 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 micrometer scale, which we term organellar crowding. Our measurements provide an initial framework of physicochemical parameters of replicatively aged yeast cells.https://elifesciences.org/articles/54707agingpHcrowdingFRET sensor
spellingShingle Sara N Mouton
David J Thaller
Matthew M Crane
Irina L Rempel
Owen T Terpstra
Anton Steen
Matt Kaeberlein
C Patrick Lusk
Arnold J Boersma
Liesbeth M Veenhoff
A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast
eLife
aging
pH
crowding
FRET sensor
title A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast
title_full A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast
title_fullStr A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast
title_full_unstemmed A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast
title_short A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast
title_sort physicochemical perspective of aging from single cell analysis of ph macromolecular and organellar crowding in yeast
topic aging
pH
crowding
FRET sensor
url https://elifesciences.org/articles/54707
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