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dc.contributor.authorBeaudoin-Chabot, Carolineen_US
dc.contributor.authorWang, Leien_US
dc.contributor.authorCelik, Cenken_US
dc.contributor.authorAishah Tul-Firdaus Abdul Khaliden_US
dc.contributor.authorThalappilly, Subhashen_US
dc.contributor.authorXu, Shiyien_US
dc.contributor.authorKoh, Jhee Hongen_US
dc.contributor.authorLim, Venus Wen Xuanen_US
dc.contributor.authorLow, Ann Donen_US
dc.contributor.authorThibault, Guillaumeen_US
dc.identifier.citationBeaudoin-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-.
dc.description.abstractMetabolic 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.en_US
dc.description.sponsorshipMinistry of Education (MOE)en_US
dc.description.sponsorshipMinistry of Health (MOH)en_US
dc.description.sponsorshipNational Medical Research Council (NMRC)en_US
dc.relation.ispartofNature Communicationsen_US
dc.rights© 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 licenses/by/4.0/.en_US
dc.titleThe unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegansen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.organizationInstitute of Molecular and Cell Biology, A*STARen_US
dc.description.versionPublished versionen_US
dc.description.acknowledgementThis 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).en_US
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