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标题：A decline in PABPN1 induces progressive muscle weakness in Oculopharyngeal muscle dystrophy and in muscle aging
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作者：Seyed Yahya Anvar ; Yotam Raz ; Nisha Verwey 等
期刊名称：Aging
出版年度：2013
卷号：5
期号：6
页码：412-426
出版社：U.S.Department of Health & Human Service
摘要：Oculopharyngeal. muscular.dystrophy. (OPMD). is. caused.by. trinucleotide.repeat.expansion.mutations.in.Poly(A)binding.protein. 1. (PABPN1).. PABPN1. is. a.regulator. of.mRNA.stability.and. is. ubiquitously.expressed..Here. we.investigatedhow.symptoms. in.OPMD.initiate.only.at.midlife.and.why.a.subset.of.skeletal.muscles.is.predominantly. affected.. Genome©\wide.RNA.expression.profiles.from.Vastus.lateralis.muscles.human.carriers. of. expanded©\PABPN1. at.pre©\symptomatic.andsymptomatic. stages. were. compared. with. healthy. controls.. Major. expression. changes. were. found. to. be. associated. withage. rather. than. with. expression. of. expanded©\PABPN1,. instead. transcriptomes. of. OPMD. and. elderly. muscles. weresignificantly.similar.(P<0.05)..Using.k©\means.clustering.we.identified.age©\dependent.trends.in.both.OPMD.and.controls,.buttrends.were. often. accelerated. in.OPMD.. We.report.an.age©\regulated.decline. in. PABPN1. levels. in. Vastus.lateralis.musclesfrom. the. fifth. decade.. In. concurrence. with. severe. muscle. degeneration. in. OPMD,. the. decline. in. PABPN1. accelerated. inOPMD.and.was.specific.to.skeletal.muscles..Reduced.PABPN1.levels.(30%.to.60%).in.muscle.cells.induced.myogenic.defectsand. morphological. signatures.of.cellular.aging. in.proportion.to.PABPN1.expression.levels.. We.suggest. that.PABPN1.levelsregulate.muscle.cell.aging.and.OPMD.represents.an.accelerated.muscle.aging.disorder
关键词：Type.2.diabetes;.TCF7L2;.centenarians;.extreme.phenotypes;.age©\related.diseases