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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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.
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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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