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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Main Authors: Beaudoin-Chabot, Caroline, Wang, Lei, Celik, Cenk, Aishah Tul-Firdaus Abdul Khalid, Thalappilly, Subhash, Xu, Shiyi, Koh, Jhee Hong, Lim, Venus Wen Xuan, Low, Ann Don, Thibault, Guillaume
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2022
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Online Access:https://hdl.handle.net/10356/162675
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spelling sg-ntu-dr.10356-1626752023-02-28T17:12:17Z The unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans Beaudoin-Chabot, Caroline Wang, Lei Celik, Cenk Aishah Tul-Firdaus Abdul Khalid Thalappilly, Subhash Xu, Shiyi Koh, Jhee Hong Lim, Venus Wen Xuan Low, Ann Don Thibault, Guillaume School of Biological Sciences Institute of Molecular and Cell Biology, A*STAR Science::Medicine Ageing Stress 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. Ministry of Education (MOE) Ministry of Health (MOH) National Medical Research Council (NMRC) Published version This work was supported by the Singapore Ministry of Education Academic Research Fund Tier 2 (2018-T2-1-002) and Tier 1 (2019-T1-002-011) as well as the Ministry of Health, Singapore, National Medical Research Council Open Fund Individual Research Grant (MOH-000566). 2022-11-04T00:29:25Z 2022-11-04T00:29:25Z 2022 Journal Article Beaudoin-Chabot, C., Wang, L., Celik, C., Aishah Tul-Firdaus Abdul Khalid, Thalappilly, S., Xu, S., Koh, J. H., Lim, V. W. X., Low, A. D. & Thibault, G. (2022). The unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans. Nature Communications, 13(1), 5889-. https://dx.doi.org/10.1038/s41467-022-33630-0 2041-1723 https://hdl.handle.net/10356/162675 10.1038/s41467-022-33630-0 36261415 2-s2.0-85140242028 1 13 5889 en 2018-T2-1-002 2019-T1-002-011 MOH-000566 Nature Communications 10.21979/N9/GEPEAG © 2022 The Author(s). 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/. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Ageing
Stress
spellingShingle Science::Medicine
Ageing
Stress
Beaudoin-Chabot, Caroline
Wang, Lei
Celik, Cenk
Aishah Tul-Firdaus Abdul Khalid
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
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.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Beaudoin-Chabot, Caroline
Wang, Lei
Celik, Cenk
Aishah Tul-Firdaus Abdul Khalid
Thalappilly, Subhash
Xu, Shiyi
Koh, Jhee Hong
Lim, Venus Wen Xuan
Low, Ann Don
Thibault, Guillaume
format Article
author Beaudoin-Chabot, Caroline
Wang, Lei
Celik, Cenk
Aishah Tul-Firdaus Abdul Khalid
Thalappilly, Subhash
Xu, Shiyi
Koh, Jhee Hong
Lim, Venus Wen Xuan
Low, Ann Don
Thibault, Guillaume
author_sort Beaudoin-Chabot, Caroline
title 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_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_sort unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized c. elegans
publishDate 2022
url https://hdl.handle.net/10356/162675
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