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Age-induced P-bodies become detrimental and shorten the lifespan of yeast

Joonhyuk Choi, Shuhao Wang, Yang Li, Nan Hao, View ORCID ProfileBrian M. Zid
doi: https://doi.org/10.1101/2021.11.05.467477
Joonhyuk Choi
1Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA
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Shuhao Wang
1Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA
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Yang Li
2Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA
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Nan Hao
2Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA
3BioCircuits Institute, University of California San Diego, La Jolla, CA 92093, USA
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Brian M. Zid
1Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA
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  • ORCID record for Brian M. Zid
  • For correspondence: zid@ucsd.edu
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Abstract

Aging is an irreversible process characterized by a progressive loss of homeostasis in cells, which often manifests as protein aggregates. Recently, it has been speculated that aggregates of RNA-binding proteins (RBPs) may go through pathological transitions during aging and drive the progression of ageassociated neurodegenerative diseases. Using Saccharomyces cerevisiae as a model system of aging, we find that P-bodies —an RBP granule that is formed and can be beneficial for cell growth during stress conditions — naturally form during aging without any external stresses and an increase in P-body intensity is negatively correlated with the future lifespan of yeast cells. When mother cells transfer age-induced P-bodies to daughter cells, the mother cells extend lifespan, while the daughter cells grow poorly, suggesting that these age-induced P-bodies may be directly pathological. Furthermore, we find that suppressing acidification of the cytosol during aging slows down the increase in the intensity of P-body foci and extends lifespan. Our data suggest that acidification of the cytosol may facilitate the pathological transition of RBP granules during aging.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 05, 2021.
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Age-induced P-bodies become detrimental and shorten the lifespan of yeast
Joonhyuk Choi, Shuhao Wang, Yang Li, Nan Hao, Brian M. Zid
bioRxiv 2021.11.05.467477; doi: https://doi.org/10.1101/2021.11.05.467477
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Age-induced P-bodies become detrimental and shorten the lifespan of yeast
Joonhyuk Choi, Shuhao Wang, Yang Li, Nan Hao, Brian M. Zid
bioRxiv 2021.11.05.467477; doi: https://doi.org/10.1101/2021.11.05.467477

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