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dc.contributor.authorTarry-Adkins, Jane Len
dc.contributor.authorFernandez-Twinn, Deniseen
dc.contributor.authorChen, Jian-Huaen
dc.contributor.authorHargreaves, Iain Pen
dc.contributor.authorNeergheen, Virunaen
dc.contributor.authorAiken, Catherineen
dc.contributor.authorOzanne, Susanen
dc.date.accessioned2018-04-05T17:33:33Z
dc.date.available2018-04-05T17:33:33Z
dc.identifier.issn1754-8403
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/274614
dc.description.abstract'Developmental programming', which occurs as a consequence of suboptimal in utero and early environments, can be associated with metabolic dysfunction in later life, including an increased incidence of cardiovascular disease and type 2 diabetes, and predisposition of older men to sarcopenia. However, the molecular mechanisms underpinning these associations are poorly understood. Many conditions associated with developmental programming are also known to be associated with the aging process. We therefore utilized our well-established rat model of low birth weight and accelerated postnatal catch-up growth (termed 'recuperated') in this study to establish the effects of suboptimal maternal nutrition on age-associated factors in skeletal muscle. We demonstrated accelerated telomere shortening (a robust marker of cellular aging) as evidenced by a reduced frequency of long telomeres (48.5-8.6 kb) and an increased frequency of short telomeres (4.2-1.3 kb) in vastus lateralis muscle from aged recuperated offspring compared to controls. This was associated with increased protein expression of the DNA-damage-repair marker 8-oxoguanine-glycosylase (OGG1) in recuperated offspring. Recuperated animals also demonstrated an oxidative stress phenotype, with decreased citrate synthase activity, increased electron-transport-complex activities of complex I, complex II-III and complex IV (all markers of functional mitochondria), and increased xanthine oxidase (XO), p67phoxand nuclear-factor kappa-light-chain-enhancer of activated B-cells (NF-κB). Recuperated offspring also demonstrated increased antioxidant defense capacity, with increased protein expression of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase and heme oxygenase-1 (HO1), all of which are known targets of NF-κB and can be upregulated as a consequence of oxidative stress. Recuperated offspring also had a pro-inflammatory phenotype, as evidenced by increased tumor necrosis factor-α (TNFα) and interleukin-1β (IL1β) protein levels. Taken together, we demonstrate, for the first time to our knowledge, an accelerated aging phenotype in skeletal muscle in the context of developmental programming. These findings may pave the way for suitable interventions in at-risk populations.
dc.description.sponsorshipThis work was supported by The British Heart Foundation [PG/09/037/27387, FS/09/029/27902]; Medical Research Council [MC_UU_12012/4] and Diabetes UK [12/0004508].
dc.languageengen
dc.publisherCompany of Biologists
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectDevelopmental programmingen
dc.subjectMitochondriaen
dc.subjectOxidative stressen
dc.subjectSkeletal muscleen
dc.subjectAgingen
dc.subjectAnimalsen
dc.subjectAntioxidantsen
dc.subjectBiomarkersen
dc.subjectDNA Damageen
dc.subjectDieten
dc.subjectFemaleen
dc.subjectGrowth and Developmenten
dc.subjectInflammationen
dc.subjectMaleen
dc.subjectMaternal Nutritional Physiological Phenomenaen
dc.subjectMuscle, Skeletalen
dc.subjectNF-kappa Ben
dc.subjectOxidantsen
dc.subjectOxidative Stressen
dc.subjectPhenotypeen
dc.subjectRats, Wistaren
dc.subjectTelomere Shorteningen
dc.titlePoor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male ratsen
dc.typeArticle
prism.endingPage1229
prism.issueIdentifier10en
prism.publicationNameDisease Models & Mechanismsen
prism.startingPage1221
prism.volume9en
dc.identifier.doi10.17863/CAM.21757
dcterms.dateAccepted2016-08-18en
rioxxterms.versionofrecord10.1242/dmm.026591en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-08-18en
dc.contributor.orcidFernandez-Twinn, Denise [0000-0003-2610-277X]
dc.contributor.orcidAiken, Catherine [0000-0002-6510-5626]
dc.contributor.orcidOzanne, Susan [0000-0001-8753-5144]
dc.identifier.eissn1754-8411
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMedical Research Council (MC_UU_12012/4)
cam.issuedOnline2016-10-05en


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