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The unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans
Metabolic diseases often share common traits, including accumulation of unfolded proteins in the endoplasmic reticulum (ER). Upon ER stress, the unfolded protein response (UPR) is activated to limit cellular damage which weakens with age. Here, we show that Caenorhabditis elegans fed a bacterial die...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582010/ https://www.ncbi.nlm.nih.gov/pubmed/36261415 http://dx.doi.org/10.1038/s41467-022-33630-0 |
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author | Beaudoin-Chabot, Caroline Wang, Lei Celik, Cenk Abdul Khalid, Aishah Tul-Firdaus Thalappilly, Subhash Xu, Shiyi Koh, Jhee Hong Lim, Venus Wen Xuan Low, Ann Don Thibault, Guillaume |
author_facet | Beaudoin-Chabot, Caroline Wang, Lei Celik, Cenk Abdul Khalid, Aishah Tul-Firdaus Thalappilly, Subhash Xu, Shiyi Koh, Jhee Hong Lim, Venus Wen Xuan Low, Ann Don Thibault, Guillaume |
author_sort | Beaudoin-Chabot, Caroline |
collection | PubMed |
description | Metabolic diseases often share common traits, including accumulation of unfolded proteins in the endoplasmic reticulum (ER). Upon ER stress, the unfolded protein response (UPR) is activated to limit cellular damage which weakens with age. Here, we show that Caenorhabditis elegans fed a bacterial diet supplemented high glucose at day 5 of adulthood (HGD-5) extends their lifespan, whereas exposed at day 1 (HGD-1) experience shortened longevity. We observed a metabolic shift only in HGD-1, while glucose and infertility synergistically prolonged the lifespan of HGD-5, independently of DAF-16. Notably, we identified that UPR stress sensors ATF-6 and PEK-1 contributed to the longevity of HGD-5 worms, while ire-1 ablation drastically increased HGD-1 lifespan. Together, we postulate that HGD activates the otherwise quiescent UPR in aged worms to overcome ageing-related stress and restore ER homeostasis. In contrast, young animals subjected to HGD provokes unresolved ER stress, conversely leading to a detrimental stress response. |
format | Online Article Text |
id | pubmed-9582010 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95820102022-10-21 The unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans Beaudoin-Chabot, Caroline Wang, Lei Celik, Cenk Abdul Khalid, Aishah Tul-Firdaus Thalappilly, Subhash Xu, Shiyi Koh, Jhee Hong Lim, Venus Wen Xuan Low, Ann Don Thibault, Guillaume Nat Commun Article Metabolic diseases often share common traits, including accumulation of unfolded proteins in the endoplasmic reticulum (ER). Upon ER stress, the unfolded protein response (UPR) is activated to limit cellular damage which weakens with age. Here, we show that Caenorhabditis elegans fed a bacterial diet supplemented high glucose at day 5 of adulthood (HGD-5) extends their lifespan, whereas exposed at day 1 (HGD-1) experience shortened longevity. We observed a metabolic shift only in HGD-1, while glucose and infertility synergistically prolonged the lifespan of HGD-5, independently of DAF-16. Notably, we identified that UPR stress sensors ATF-6 and PEK-1 contributed to the longevity of HGD-5 worms, while ire-1 ablation drastically increased HGD-1 lifespan. Together, we postulate that HGD activates the otherwise quiescent UPR in aged worms to overcome ageing-related stress and restore ER homeostasis. In contrast, young animals subjected to HGD provokes unresolved ER stress, conversely leading to a detrimental stress response. Nature Publishing Group UK 2022-10-19 /pmc/articles/PMC9582010/ /pubmed/36261415 http://dx.doi.org/10.1038/s41467-022-33630-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Beaudoin-Chabot, Caroline Wang, Lei Celik, Cenk Abdul Khalid, Aishah Tul-Firdaus Thalappilly, Subhash Xu, Shiyi Koh, Jhee Hong Lim, Venus Wen Xuan Low, Ann Don Thibault, Guillaume The unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans |
title | The unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans |
title_full | The unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans |
title_fullStr | The unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans |
title_full_unstemmed | The unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans |
title_short | The unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans |
title_sort | unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized c. elegans |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9582010/ https://www.ncbi.nlm.nih.gov/pubmed/36261415 http://dx.doi.org/10.1038/s41467-022-33630-0 |
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