Ítem
Acceso Abierto

Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice

Mostrar el registro sencillo de la publicación
dc.creatorVermeij, W. P.spa
dc.creatorDollé, M. E. T.spa
dc.creatorReiling, E.spa
dc.creatorJaarsma, D.spa
dc.creatorPayan-Gomez, Cesarspa
dc.creatorBombardieri, C. R.spa
dc.creatorWu, H.spa
dc.creatorRoks, A. J. M.spa
dc.creatorBotter, S. M.spa
dc.creatorvan der Eerden, B. C.spa
dc.creatorYoussef, S. A.spa
dc.creatorKuiper, R. V.spa
dc.creatorNagarajah, B.spa
dc.creatorvan Oostrom, C. T.spa
dc.creatorBrandt, R. M. C.spa
dc.creatorBarnhoorn, S.spa
dc.creatorImholz, S.spa
dc.creatorPennings, J. L. A.spa
dc.creatorde Bruin, A.spa
dc.creatorGyenis, Á.spa
dc.creatorPothof, J.spa
dc.creatorVijg, J.spa
dc.creatorvan Steeg, H.spa
dc.creatorHoeijmakers, J. H. J.spa
dc.date.accessioned2020-05-25T23:57:20Z
dc.date.available2020-05-25T23:57:20Z
dc.date.created2016spa
dc.description.abstractMice deficient in the DNA excision-repair gene Ercc1 (Ercc1?/-) show numerous accelerated ageing features that limit their lifespan to 4-6 months. They also exhibit a 'survival response', which suppresses growth and enhances cellular maintenance. Such a response resembles the anti-ageing response induced by dietary restriction (also known as caloric restriction). Here we report that a dietary restriction of 30% tripled the median and maximal remaining lifespans of these progeroid mice, strongly retarding numerous aspects of accelerated ageing. Mice undergoing dietary restriction retained 50% more neurons and maintained full motor function far beyond the lifespan of mice fed ad libitum. Other DNA-repair-deficient, progeroid Xpg-/- (also known as Ercc5-/-) mice, a model of Cockayne syndrome, responded similarly. The dietary restriction response in Ercc1?/- mice closely resembled the effects of dietary restriction in wild-type animals. Notably, liver tissue from Ercc1?/- mice fed ad libitum showed preferential extinction of the expression of long genes, a phenomenon we also observed in several tissues ageing normally. This is consistent with the accumulation of stochastic, transcription-blocking lesions that affect long genes more than short ones. Dietary restriction largely prevented this declining transcriptional output and reduced the number of ?H2AX DNA damage foci, indicating that dietary restriction preserves genome function by alleviating DNA damage. Our findings establish the Ercc1?/- mouse as a powerful model organism for health-sustaining interventions, reveal potential for reducing endogenous DNA damage, facilitate a better understanding of the molecular mechanism of dietary restriction and suggest a role for counterintuitive dietary-restriction-like therapy for human progeroid genome instability syndromes and possibly neurodegeneration in general. © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1038/nature19329
dc.identifier.issn14764687
dc.identifier.issn00280836
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/22646
dc.language.isoengspa
dc.publisherNature Publishing Groupspa
dc.relation.citationEndPage431
dc.relation.citationIssueNo. 7620
dc.relation.citationStartPage427
dc.relation.citationTitleNature
dc.relation.citationVolumeVol. 537
dc.relation.ispartofNature, ISSN:14764687, 00280836, Vol.537, No.7620 (2016); pp. 427-431spa
dc.relation.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84984633161&doi=10.1038%2fnature19329&partnerID=40&md5=c174c987afb726481520cbf655356998spa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subject.keywordAgingspa
dc.subject.keywordmouseeng
dc.subject.keywordCells and cell componentsspa
dc.subject.keywordreducingeng
dc.subject.keywordDamagespa
dc.subject.keywordDietspa
dc.subject.keywordDnaspa
dc.subject.keywordGene expressionspa
dc.subject.keywordGenomespa
dc.subject.keywordGenomicsspa
dc.subject.keywordRodentspa
dc.subject.keywordAnimaliaspa
dc.subject.keywordMusspa
dc.subject.keywordDna binding proteinspa
dc.subject.keywordDna excision repair protein ercc-5spa
dc.subject.keywordEndonucleasespa
dc.subject.keywordErcc1 proteineng
dc.subject.keywordNuclear proteinspa
dc.subject.keywordTranscription factorspa
dc.subject.keywordTranscriptomespa
dc.subject.keywordAgingspa
dc.subject.keywordAnimalspa
dc.subject.keywordBrainspa
dc.subject.keywordCaloric restrictionspa
dc.subject.keywordDeficiencyspa
dc.subject.keywordDna damagespa
dc.subject.keywordDna repairspa
dc.subject.keywordFemalespa
dc.subject.keywordGeneticsspa
dc.subject.keywordGenomic instabilityspa
dc.subject.keywordLow calory dietspa
dc.subject.keywordMalespa
dc.subject.keywordMousespa
dc.subject.keywordNeurodegenerative diseasesspa
dc.subject.keywordPhysiologyspa
dc.subject.keywordAgingspa
dc.subject.keywordAnimalsspa
dc.subject.keywordBrainspa
dc.subject.keywordCaloric restrictionspa
dc.subject.keywordDieteng
dc.subject.keywordDna damagespa
dc.subject.keywordDna repairspa
dc.subject.keywordDna-binding proteinsspa
dc.subject.keywordEndonucleasesspa
dc.subject.keywordFemalespa
dc.subject.keywordGenomic instabilityspa
dc.subject.keywordMalespa
dc.subject.keywordMicespa
dc.subject.keywordNeurodegenerative diseasesspa
dc.subject.keywordNuclear proteinsspa
dc.subject.keywordTranscription factorsspa
dc.subject.keywordTranscriptomespa
dc.titleRestricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient micespa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
Archivos
Bloque original
Mostrando1 - 1 de 1
Miniatura
Nombre:
nature19329.pdf
Tamaño:
5.01 MB
Formato:
Adobe Portable Document Format
Descripción:
Descargar
Colecciones
Artículos