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dc.contributor.authorGomes, Ana P.
dc.contributor.authorPrice, Nathan L.
dc.contributor.authorLing, Alvin J.Y.
dc.contributor.authorMoslehi, Javid
dc.contributor.authorMontgomery, Magdalene K.
dc.contributor.authorRajman, Luis
dc.contributor.authorWhite, James Patrick
dc.contributor.authorTeodoro, João S.
dc.contributor.authorWrann, Christiane Dorothea
dc.contributor.authorHubbard, Basil P.
dc.contributor.authorMercken, Evi M.
dc.contributor.authorPalmeira, Carlos M.
dc.contributor.authorde Cabo, Rafael
dc.contributor.authorRolo, Anabela P.
dc.contributor.authorTurner, Nigel
dc.contributor.authorBell, Eric L.
dc.contributor.authorSinclair, David Andrew
dc.date.accessioned2017-04-26T15:52:32Z
dc.date.issued2013
dc.identifierQuick submit: 2014-01-09T09:09:24-05:00
dc.identifier.citationGomes, Ana P., Nathan L. Price, Alvin J.Y. Ling, Javid J. Moslehi, Magdalene K. Montgomery, Luis Rajman, James P. White, et al. 2013. Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication During Aging. Cell 155(7): 1624–1638.en_US
dc.identifier.issn0092-8674en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:32491128
dc.description.abstractEver since eukaryotes subsumed the bacterial ancestor of mitochondria, the nuclear and mitochondrial genomes have had to closely coordinate their activities, as each encode different subunits of the oxidative phosphorylation (OXPHOS) system. Mitochondrial dysfunction is a hallmark of aging, but its causes are debated. We show that, during aging, there is a specific loss of mitochondrial, but not nuclear, encoded OXPHOS subunits. We trace the cause to an alternate PGC-1α/β-independent pathway of nuclear-mitochondrial communication that is induced by a decline in nuclear NAD+ and the accumulation of HIF-1α under normoxic conditions, with parallels to Warburg reprogramming. Deleting SIRT1 accelerates this process, whereas raising NAD+ levels in old mice restores mitochondrial function to that of a young mouse in a SIRT1-dependent manner. Thus, a pseudohypoxic state that disrupts PGC-1α/β-independent nuclear-mitochondrial communication contributes to the decline in mitochondrial function with age, a process that is apparently reversible.en_US
dc.language.isoen_USen_US
dc.publisherElsevier BVen_US
dc.relation.isversionofdoi:10.1016/j.cell.2013.11.037en_US
dc.relation.hasversionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076149/en_US
dash.licenseLAA
dc.titleDeclining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Agingen_US
dc.typeJournal Articleen_US
dc.date.updated2014-01-09T14:10:44Z
dc.description.versionAccepted Manuscripten_US
dc.rights.holderGomes et al.
dc.relation.journalCellen_US
dash.depositing.authorSinclair, David Andrew
dc.date.available2017-04-26T15:52:32Z
dc.identifier.doi10.1016/j.cell.2013.11.037*
dash.authorsorderedfalse
dash.contributor.affiliatedWrann, Christiane
dash.contributor.affiliatedWhite, James Patrick
dash.contributor.affiliatedMoslehi, Javid
dash.contributor.affiliatedSinclair, David


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