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dc.contributor.authorHwang, Inahen_US
dc.contributor.authorOh, Hwanheeen_US
dc.contributor.authorSanto, Evanen_US
dc.contributor.authorKim, Do‐Yeonen_US
dc.contributor.authorChen, John W.en_US
dc.contributor.authorBronson, Roderick T.en_US
dc.contributor.authorLocasale, Jason W.en_US
dc.contributor.authorNa, Yoonmien_US
dc.contributor.authorLee, Jaclynen_US
dc.contributor.authorReed, Stewarten_US
dc.contributor.authorToth, Miklosen_US
dc.contributor.authorYu, Wai H.en_US
dc.contributor.authorMuller, Florian L.en_US
dc.contributor.authorPaik, Jihyeen_US
dc.date.accessioned2018-03-20T16:01:28Z
dc.date.issued2017en_US
dc.identifier.citationHwang, I., H. Oh, E. Santo, D. Kim, J. W. Chen, R. T. Bronson, J. W. Locasale, et al. 2017. “FOXO protects against age‐progressive axonal degeneration.” Aging Cell 17 (1): e12701. doi:10.1111/acel.12701. http://dx.doi.org/10.1111/acel.12701.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:35014853
dc.description.abstractSummary Neurodegeneration resulting in cognitive and motor impairment is an inevitable consequence of aging. Little is known about the genetic regulation of this process despite its overriding importance in normal aging. Here, we identify the Forkhead Box O (FOXO) transcription factor 1, 3, and 4 isoforms as a guardian of neuronal integrity by inhibiting age‐progressive axonal degeneration in mammals. FOXO expression progressively increased in aging human and mouse brains. The nervous system‐specific deletion of Foxo transcription factors in mice accelerates aging‐related axonal tract degeneration, which is followed by motor dysfunction. This accelerated neurodegeneration is accompanied by levels of white matter astrogliosis and microgliosis in middle‐aged Foxo knockout mice that are typically only observed in very old wild‐type mice and other aged mammals, including humans. Mechanistically, axonal degeneration in nerve‐specific Foxo knockout mice is associated with elevated mTORC1 activity and accompanying proteotoxic stress due to decreased Sestrin3 expression. Inhibition of mTORC1 by rapamycin treatment mimics FOXO action and prevented axonal degeneration in Foxo knockout mice with accelerated nervous system aging. Defining this central role for FOXO in neuroprotection during mammalian aging offers an invaluable window into the aging process itself.en
dc.language.isoen_USen
dc.publisherJohn Wiley and Sons Inc.en
dc.relation.isversionofdoi:10.1111/acel.12701en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771393/pdf/en
dash.licenseLAAen_US
dc.subjectOriginal Articleen
dc.subjectaccelerated agingen
dc.subjectagingen
dc.subjectcentral nervous systemen
dc.subjecten
dc.subjectmouse modelsen
dc.subjectneurodegenerationen
dc.subjectneuroinflammationen
dc.subjectoxidative stressen
dc.titleFOXO protects against age‐progressive axonal degenerationen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalAging Cellen
dash.depositing.authorChen, John W.en_US
dc.date.available2018-03-20T16:01:28Z
dc.identifier.doi10.1111/acel.12701*
dash.authorsorderedfalse
dash.contributor.affiliatedChen, John
dash.contributor.affiliatedBronson, Roderick


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