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dc.contributor.authorMouchiroud, Laurent
dc.contributor.authorHoutkooper, Riekelt H.
dc.contributor.authorMoullan, Norman
dc.contributor.authorKatsyuba, Elena
dc.contributor.authorRyu, Dongryeol
dc.contributor.authorCanto, Carles
dc.contributor.authorMottis, Adrienne
dc.contributor.authorJo, Young-Suk
dc.contributor.authorViswanathan, Mohan
dc.contributor.authorSchoonjans, Kristina
dc.contributor.authorAuwerx, Johan
dc.contributor.authorGuarente, Leonard Pershing
dc.date.accessioned2015-04-07T17:38:20Z
dc.date.available2015-04-07T17:38:20Z
dc.date.issued2013-07
dc.date.submitted2013-04
dc.identifier.issn00928674
dc.identifier.issn1097-4172
dc.identifier.urihttp://hdl.handle.net/1721.1/96399
dc.description.abstractNAD[superscript +] is an important cofactor regulating metabolic homeostasis and a rate-limiting substrate for sirtuin deacylases. We show that NAD[superscript +] levels are reduced in aged mice and Caenorhabditis elegans and that decreasing NAD[superscript +] levels results in a further reduction in worm lifespan. Conversely, genetic or pharmacological restoration of NAD[superscript +] prevents age-associated metabolic decline and promotes longevity in worms. These effects are dependent upon the protein deacetylase sir-2.1 and involve the induction of mitonuclear protein imbalance as well as activation of stress signaling via the mitochondrial unfolded protein response (UPR[superscript mt]) and the nuclear translocation and activation of FOXO transcription factor DAF-16. Our data suggest that augmenting mitochondrial stress signaling through the modulation of NAD[superscript +] levels may be a target to improve mitochondrial function and prevent or treat age-associated decline.en_US
dc.description.sponsorshipÉcole polytechnique fédérale de Lausanneen_US
dc.description.sponsorshipEuropean Union. Ideas Program (ERC-2008-AdG-23138)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant R01HL106511-01A)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant R01AG043930)en_US
dc.description.sponsorshipVelux Stiftungen_US
dc.description.sponsorshipSwiss National Science Foundation (Grant 31003A-124713)en_US
dc.description.sponsorshipSwiss National Science Foundation (Grant 31003A-125487)en_US
dc.description.sponsorshipSwiss National Science Foundation (Grant CSRII3-136201)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.cell.2013.06.016en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceElsevier Open Archiveen_US
dc.titleThe [NAD[superscript +] over Sirtuin] Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signalingen_US
dc.typeArticleen_US
dc.identifier.citationMouchiroud, Laurent, Riekelt H. Houtkooper, Norman Moullan, Elena Katsyuba, Dongryeol Ryu, Carles Cantó, Adrienne Mottis, et al. “The [NAD[superscript +] over Sirtuin] Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling.” Cell 154, no. 2 (July 2013): 430–441. © 2013 Elsevier Inc.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentPaul F. Glenn Center for Biology of Aging Research (Massachusetts Institute of Technology)en_US
dc.contributor.mitauthorViswanathan, Mohanen_US
dc.contributor.mitauthorGuarente, Leonard Pershingen_US
dc.relation.journalCellen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsMouchiroud, Laurent; Houtkooper, Riekelt H.; Moullan, Norman; Katsyuba, Elena; Ryu, Dongryeol; Cantó, Carles; Mottis, Adrienne; Jo, Young-Suk; Viswanathan, Mohan; Schoonjans, Kristina; Guarente, Leonard; Auwerx, Johanen_US
dc.identifier.orcidhttps://orcid.org/0000-0003-4064-2510
mit.licensePUBLISHER_POLICYen_US


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