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dc.contributor.authorNeumann, Bjornen
dc.contributor.authorBaror, Roeyen
dc.contributor.authorZhao, Chaoen
dc.contributor.authorSegel, Michaelen
dc.contributor.authorDietmann, Sabineen
dc.contributor.authorRawji, Khalil Sen
dc.contributor.authorFoerster, Sarahen
dc.contributor.authorMcClain, Crystal Ren
dc.contributor.authorChalut, Kevinen
dc.contributor.authorvan Wijngaarden, Peteren
dc.contributor.authorFranklin, Robinen
dc.date.accessioned2019-09-03T23:30:49Z
dc.date.available2019-09-03T23:30:49Z
dc.date.issued2019-10en
dc.identifier.issn1934-5909
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/296382
dc.description.abstractThe age-related failure to produce oligodendrocytes from oligodendrocyte progenitor cells (OPCs) is associated with irreversible neurodegeneration in multiple sclerosis (MS). Consequently, regenerative approaches have significant potential for treating for chronic demyelinating diseases. Here, we show that the differentiation potential of adult rodent OPCs decreases with age. Aged OPCs become unresponsive to pro-differentiation signals, suggesting intrinsic constraints on therapeutic approaches aimed at enhancing OPC differentiation. This decline in functional capacity is associated with hallmarks of cellular aging including decreased metabolic function and increased DNA damage. Fasting or treatment with metformin can reverse these changes and restore regenerative capacity of aged OPCs, improving remyelination in aged animals following focal demyelination injuries. Aged OPCs treated with metformin regain responsiveness to pro-differentiation signals, suggesting synergistic effects of rejuvenation and pro-differentiation therapies. These findings provide insight into aging-associated remyelination failure and suggest therapeutic interventions for reversing such declines in chronic disease.
dc.description.sponsorshipThis work was supported by funding from the UK Multiple Sclerosis Society, MedImmune, The Adelson Medical Research Foundation and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute. We thank Dr Daniel Morrison for assistance with the electron microscopy, the NIHR Cambridge BRC Cell Phenotyping Hub for all flow cytometry work and staff at the Cambridge Advanced Imaging Centre.
dc.format.mediumPrinten
dc.languageengen
dc.publisherElsevier
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectCentral Nervous Systemen
dc.subjectOligodendrogliaen
dc.subjectCells, Cultureden
dc.subjectAnimalsen
dc.subjectHumansen
dc.subjectRatsen
dc.subjectMultiple Sclerosisen
dc.subjectDNA Damageen
dc.subjectMetforminen
dc.subjectHypoglycemic Agentsen
dc.subjectRejuvenationen
dc.subjectStem Cell Transplantationen
dc.subjectCell Differentiationen
dc.subjectAgingen
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectOligodendrocyte Precursor Cellsen
dc.subjectRemyelinationen
dc.titleMetformin Restores CNS Remyelination Capacity by Rejuvenating Aged Stem Cells.en
dc.typeArticle
prism.endingPage485.e8
prism.issueIdentifier4en
prism.publicationDate2019en
prism.publicationNameCell stem cellen
prism.startingPage473
prism.volume25en
dc.identifier.doi10.17863/CAM.43431
dcterms.dateAccepted2019-08-23en
rioxxterms.versionofrecord10.1016/j.stem.2019.08.015en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-10en
dc.contributor.orcidZhao, Chao [0000-0003-1144-1621]
dc.contributor.orcidDietmann, Sabine [0000-0001-6672-8457]
dc.contributor.orcidFoerster, Sarah [0000-0002-2585-0621]
dc.contributor.orcidChalut, Kevin [0000-0001-6200-9690]
dc.contributor.orcidFranklin, Robin [0000-0001-6522-2104]
dc.identifier.eissn1875-9777
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idDr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF) (unknown)
pubs.funder-project-idMRC (MC_PC_12009)
cam.orpheus.successThu Jan 30 10:39:42 GMT 2020 - Embargo updated*
rioxxterms.freetoread.startdate2020-10-31


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International