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IRE-1 endoribonuclease activity declines early in C. elegans adulthood and is not rescued by reduced reproduction

The proteome of a cell helps to define its functional specialization. Most proteins must be translated and properly folded to ensure their biological function, but with aging, animals lose their ability to maintain a correctly folded proteome. This leads to the accumulation of protein aggregates, de...

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Autores principales: De-Souza, Evandro A., Cummins, Nadia, Taylor, Rebecca C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9649906/
https://www.ncbi.nlm.nih.gov/pubmed/36389122
http://dx.doi.org/10.3389/fragi.2022.1044556
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author De-Souza, Evandro A.
Cummins, Nadia
Taylor, Rebecca C.
author_facet De-Souza, Evandro A.
Cummins, Nadia
Taylor, Rebecca C.
author_sort De-Souza, Evandro A.
collection PubMed
description The proteome of a cell helps to define its functional specialization. Most proteins must be translated and properly folded to ensure their biological function, but with aging, animals lose their ability to maintain a correctly folded proteome. This leads to the accumulation of protein aggregates, decreased stress resistance, and the onset of age-related disorders. The unfolded protein response of the endoplasmic reticulum (UPR(ER)) is a central protein quality control mechanism, the function of which is known to decline with age. Here, we show that age-related UPR(ER) decline in Caenorhabditis elegans occurs at the onset of the reproductive period and is caused by a failure in IRE-1 endoribonuclease activities, affecting both the splicing of xbp-1 mRNA and regulated Ire1 dependent decay (RIDD) activity. Animals with a defect in germline development, previously shown to rescue the transcriptional activity of other stress responses during aging, do not show restored UPR(ER) activation with age. This underlines the mechanistic difference between age-associated loss of UPR(ER) activation and that of other stress responses in this system, and uncouples reproductive status from the activity of somatic maintenance pathways. These observations may aid in the development of strategies that aim to overcome the proteostasis decline observed with aging.
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spelling pubmed-96499062022-11-15 IRE-1 endoribonuclease activity declines early in C. elegans adulthood and is not rescued by reduced reproduction De-Souza, Evandro A. Cummins, Nadia Taylor, Rebecca C. Front Aging Aging The proteome of a cell helps to define its functional specialization. Most proteins must be translated and properly folded to ensure their biological function, but with aging, animals lose their ability to maintain a correctly folded proteome. This leads to the accumulation of protein aggregates, decreased stress resistance, and the onset of age-related disorders. The unfolded protein response of the endoplasmic reticulum (UPR(ER)) is a central protein quality control mechanism, the function of which is known to decline with age. Here, we show that age-related UPR(ER) decline in Caenorhabditis elegans occurs at the onset of the reproductive period and is caused by a failure in IRE-1 endoribonuclease activities, affecting both the splicing of xbp-1 mRNA and regulated Ire1 dependent decay (RIDD) activity. Animals with a defect in germline development, previously shown to rescue the transcriptional activity of other stress responses during aging, do not show restored UPR(ER) activation with age. This underlines the mechanistic difference between age-associated loss of UPR(ER) activation and that of other stress responses in this system, and uncouples reproductive status from the activity of somatic maintenance pathways. These observations may aid in the development of strategies that aim to overcome the proteostasis decline observed with aging. Frontiers Media S.A. 2022-10-28 /pmc/articles/PMC9649906/ /pubmed/36389122 http://dx.doi.org/10.3389/fragi.2022.1044556 Text en Copyright © 2022 De-Souza, Cummins and Taylor. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Aging
De-Souza, Evandro A.
Cummins, Nadia
Taylor, Rebecca C.
IRE-1 endoribonuclease activity declines early in C. elegans adulthood and is not rescued by reduced reproduction
title IRE-1 endoribonuclease activity declines early in C. elegans adulthood and is not rescued by reduced reproduction
title_full IRE-1 endoribonuclease activity declines early in C. elegans adulthood and is not rescued by reduced reproduction
title_fullStr IRE-1 endoribonuclease activity declines early in C. elegans adulthood and is not rescued by reduced reproduction
title_full_unstemmed IRE-1 endoribonuclease activity declines early in C. elegans adulthood and is not rescued by reduced reproduction
title_short IRE-1 endoribonuclease activity declines early in C. elegans adulthood and is not rescued by reduced reproduction
title_sort ire-1 endoribonuclease activity declines early in c. elegans adulthood and is not rescued by reduced reproduction
topic Aging
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9649906/
https://www.ncbi.nlm.nih.gov/pubmed/36389122
http://dx.doi.org/10.3389/fragi.2022.1044556
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