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dc.contributor.authorAnderson, Edward N.
dc.contributor.authorCorkins, Mark E.
dc.contributor.authorLi, Jia Cheng
dc.contributor.authorSingh, Komudi
dc.contributor.authorParsons, Sadé
dc.contributor.authorTucey, Tim M.
dc.contributor.authorSorkaç, Altar
dc.contributor.authorHuang, Huiyan
dc.contributor.authorDimitriadi, Maria
dc.contributor.authorSinclair, David A.
dc.contributor.authorHart, Anne C.
dc.identifier.citationAnderson , E N , Corkins , M E , Li , J C , Singh , K , Parsons , S , Tucey , T M , Sorkaç , A , Huang , H , Dimitriadi , M , Sinclair , D A & Hart , A C 2016 , ' C. elegans lifespan extension by osmotic stress requires FUdR, base excision repair, FOXO, and sirtuins ' , Mechanisms of Ageing and Development , vol. 154 , pp. 30-42 .
dc.identifier.otherPURE: 10101287
dc.identifier.otherPURE UUID: b4eb7dd2-68ea-4086-96d5-f286fc819fe0
dc.identifier.otherScopus: 84958535552
dc.description.abstractModerate stress can increase lifespan by hormesis, a beneficial low-level induction of stress response pathways. 5'-fluorodeoxyuridine (FUdR) is commonly used to sterilize Caenorhabditis elegans in aging experiments. However, FUdR alters lifespan in some genotypes and induces resistance to thermal and proteotoxic stress. We report that hypertonic stress in combination with FUdR treatment or inhibition of the FUdR target thymidylate synthase, TYMS-1, extends C. elegans lifespan by up to 30%. By contrast, in the absence of FUdR, hypertonic stress decreases lifespan. Adaptation to hypertonic stress requires diminished Notch signaling and loss of Notch co-ligands leads to lifespan extension only in combination with FUdR. Either FUdR treatment or TYMS-1 loss induced resistance to acute hypertonic stress, anoxia, and thermal stress. FUdR treatment increased expression of DAF-16 FOXO and the osmolyte biosynthesis enzyme GPDH-1. FUdR-induced hypertonic stress resistance was partially dependent on sirtuins and base excision repair (BER) pathways, while FUdR-induced lifespan extension under hypertonic stress conditions requires DAF-16, BER, and sirtuin function. Combined, these results demonstrate that FUdR, through inhibition of TYMS-1, activates stress response pathways in somatic tissues to confer hormetic resistance to acute and chronic stress. C. elegans lifespan studies using FUdR may need re-interpretation in light of this work.en
dc.relation.ispartofMechanisms of Ageing and Development
dc.subjectC. elegans
dc.subjectHypertonic stress
dc.subjectDevelopmental Biology
dc.titleC. elegans lifespan extension by osmotic stress requires FUdR, base excision repair, FOXO, and sirtuinsen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionDepartment of Biological and Environmental Sciences
dc.contributor.institutionGeography, Environment and Agriculture
dc.contributor.institutionBiosciences Research Group
dc.contributor.institutionWeight and Obesity Research Group
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
rioxxterms.typeJournal Article/Review

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