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The synergy of damage repair and retention promotes rejuvenation and prolongs healthy lifespans in cell lineages

Damaged proteins are inherited asymmetrically during cell division in the yeast Saccharomyces cerevisiae, such that most damage is retained within the mother cell. The consequence is an ageing mother and a rejuvenated daughter cell with full replicative potential. Daughters of old and damaged mother...

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Autores principales: Schnitzer, Barbara, Borgqvist, Johannes, Cvijovic, Marija
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598927/
https://www.ncbi.nlm.nih.gov/pubmed/33044956
http://dx.doi.org/10.1371/journal.pcbi.1008314
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author Schnitzer, Barbara
Borgqvist, Johannes
Cvijovic, Marija
author_facet Schnitzer, Barbara
Borgqvist, Johannes
Cvijovic, Marija
author_sort Schnitzer, Barbara
collection PubMed
description Damaged proteins are inherited asymmetrically during cell division in the yeast Saccharomyces cerevisiae, such that most damage is retained within the mother cell. The consequence is an ageing mother and a rejuvenated daughter cell with full replicative potential. Daughters of old and damaged mothers are however born with increasing levels of damage resulting in lowered replicative lifespans. Remarkably, these prematurely old daughters can give rise to rejuvenated cells with low damage levels and recovered lifespans, called second-degree rejuvenation. We aimed to investigate how damage repair and retention together can promote rejuvenation and at the same time ensure low damage levels in mother cells, reflected in longer health spans. We developed a dynamic model for damage accumulation over successive divisions in individual cells as part of a dynamically growing cell lineage. With detailed knowledge about single-cell dynamics and relationships between all cells in the lineage, we can infer how individual damage repair and retention strategies affect the propagation of damage in the population. We show that damage retention lowers damage levels in the population by reducing the variability across the lineage, and results in larger population sizes. Repairing damage efficiently in early life, as opposed to investing in repair when damage has already accumulated, counteracts accelerated ageing caused by damage retention. It prolongs the health span of individual cells which are moreover less prone to stress. In combination, damage retention and early investment in repair are beneficial for healthy ageing in yeast cell populations.
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spelling pubmed-75989272020-11-03 The synergy of damage repair and retention promotes rejuvenation and prolongs healthy lifespans in cell lineages Schnitzer, Barbara Borgqvist, Johannes Cvijovic, Marija PLoS Comput Biol Research Article Damaged proteins are inherited asymmetrically during cell division in the yeast Saccharomyces cerevisiae, such that most damage is retained within the mother cell. The consequence is an ageing mother and a rejuvenated daughter cell with full replicative potential. Daughters of old and damaged mothers are however born with increasing levels of damage resulting in lowered replicative lifespans. Remarkably, these prematurely old daughters can give rise to rejuvenated cells with low damage levels and recovered lifespans, called second-degree rejuvenation. We aimed to investigate how damage repair and retention together can promote rejuvenation and at the same time ensure low damage levels in mother cells, reflected in longer health spans. We developed a dynamic model for damage accumulation over successive divisions in individual cells as part of a dynamically growing cell lineage. With detailed knowledge about single-cell dynamics and relationships between all cells in the lineage, we can infer how individual damage repair and retention strategies affect the propagation of damage in the population. We show that damage retention lowers damage levels in the population by reducing the variability across the lineage, and results in larger population sizes. Repairing damage efficiently in early life, as opposed to investing in repair when damage has already accumulated, counteracts accelerated ageing caused by damage retention. It prolongs the health span of individual cells which are moreover less prone to stress. In combination, damage retention and early investment in repair are beneficial for healthy ageing in yeast cell populations. Public Library of Science 2020-10-12 /pmc/articles/PMC7598927/ /pubmed/33044956 http://dx.doi.org/10.1371/journal.pcbi.1008314 Text en © 2020 Schnitzer et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Schnitzer, Barbara
Borgqvist, Johannes
Cvijovic, Marija
The synergy of damage repair and retention promotes rejuvenation and prolongs healthy lifespans in cell lineages
title The synergy of damage repair and retention promotes rejuvenation and prolongs healthy lifespans in cell lineages
title_full The synergy of damage repair and retention promotes rejuvenation and prolongs healthy lifespans in cell lineages
title_fullStr The synergy of damage repair and retention promotes rejuvenation and prolongs healthy lifespans in cell lineages
title_full_unstemmed The synergy of damage repair and retention promotes rejuvenation and prolongs healthy lifespans in cell lineages
title_short The synergy of damage repair and retention promotes rejuvenation and prolongs healthy lifespans in cell lineages
title_sort synergy of damage repair and retention promotes rejuvenation and prolongs healthy lifespans in cell lineages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598927/
https://www.ncbi.nlm.nih.gov/pubmed/33044956
http://dx.doi.org/10.1371/journal.pcbi.1008314
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