{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670320809304320.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.0508886102"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.0508886102"}},{"identifier":{"@type":"NAID","@value":"30016242869"}}],"dc:title":[{"@value":"Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>\n            The mitochondrial theory of aging proposes that reactive oxygen species (ROS) generated inside the cell will lead, with time, to increasing amounts of oxidative damage to various cell components. The main site for ROS production is the respiratory chain inside the mitochondria and accumulation of mtDNA mutations, and impaired respiratory chain function have been associated with degenerative diseases and aging. The theory predicts that impaired respiratory chain function will augment ROS production and thereby increase the rate of mtDNA mutation accumulation, which, in turn, will further compromise respiratory chain function. Previously, we reported that mice expressing an error-prone version of the catalytic subunit of mtDNA polymerase accumulate a substantial burden of somatic mtDNA mutations, associated with premature aging phenotypes and reduced lifespan. Here we show that these mtDNA mutator mice accumulate mtDNA mutations in an approximately linear manner. The amount of ROS produced was normal, and no increased sensitivity to oxidative stress-induced cell death was observed in mouse embryonic fibroblasts from mtDNA mutator mice, despite the presence of a severe respiratory chain dysfunction. Expression levels of antioxidant defense enzymes, protein carbonylation levels, and aconitase enzyme activity measurements indicated no or only minor oxidative stress in tissues from mtDNA mutator mice. The premature aging phenotypes in mtDNA mutator mice are thus not generated by a vicious cycle of massively increased oxidative stress accompanied by exponential accumulation of mtDNA mutations. We propose instead that respiratory chain dysfunction\n            <jats:italic>per se</jats:italic>\n            is the primary inducer of premature aging in mtDNA mutator mice.\n          </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380857673294983811","@type":"Researcher","foaf:name":[{"@value":"Aleksandra Trifunovic"}],"jpcoar:affiliationName":[{"@value":"Department of Laboratory Medicine, Karolinska Institute, S-141 86 Stockholm, Sweden; and Institute of Medical Technology and Tampere University Hospital, FI-33014 University of Tampere, Finland"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857673294983813","@type":"Researcher","foaf:name":[{"@value":"Anna Hansson"}],"jpcoar:affiliationName":[{"@value":"Department of Laboratory Medicine, Karolinska Institute, S-141 86 Stockholm, Sweden; and Institute of Medical Technology and Tampere University Hospital, FI-33014 University of Tampere, Finland"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857673294983809","@type":"Researcher","foaf:name":[{"@value":"Anna Wredenberg"}],"jpcoar:affiliationName":[{"@value":"Department of Laboratory Medicine, Karolinska Institute, S-141 86 Stockholm, Sweden; and Institute of Medical Technology and Tampere University Hospital, FI-33014 University of Tampere, Finland"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857673294983816","@type":"Researcher","foaf:name":[{"@value":"Anja T. Rovio"}],"jpcoar:affiliationName":[{"@value":"Department of Laboratory Medicine, Karolinska Institute, S-141 86 Stockholm, Sweden; and Institute of Medical Technology and Tampere University Hospital, FI-33014 University of Tampere, Finland"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857673294983812","@type":"Researcher","foaf:name":[{"@value":"Eric Dufour"}],"jpcoar:affiliationName":[{"@value":"Department of Laboratory Medicine, Karolinska Institute, S-141 86 Stockholm, Sweden; and Institute of Medical Technology and Tampere University Hospital, FI-33014 University of Tampere, Finland"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857673294983815","@type":"Researcher","foaf:name":[{"@value":"Ivan Khvorostov"}],"jpcoar:affiliationName":[{"@value":"Department of Laboratory Medicine, Karolinska Institute, S-141 86 Stockholm, Sweden; and Institute of Medical Technology and Tampere University Hospital, FI-33014 University of Tampere, Finland"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857673294983810","@type":"Researcher","foaf:name":[{"@value":"Johannes N. Spelbrink"}],"jpcoar:affiliationName":[{"@value":"Department of Laboratory Medicine, Karolinska Institute, S-141 86 Stockholm, Sweden; and Institute of Medical Technology and Tampere University Hospital, FI-33014 University of Tampere, Finland"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857673294983808","@type":"Researcher","foaf:name":[{"@value":"Rolf Wibom"}],"jpcoar:affiliationName":[{"@value":"Department of Laboratory Medicine, Karolinska Institute, S-141 86 Stockholm, Sweden; and Institute of Medical Technology and Tampere University Hospital, FI-33014 University of Tampere, Finland"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857673294983814","@type":"Researcher","foaf:name":[{"@value":"Howard T. Jacobs"}],"jpcoar:affiliationName":[{"@value":"Department of Laboratory Medicine, Karolinska Institute, S-141 86 Stockholm, Sweden; and Institute of Medical Technology and Tampere University Hospital, FI-33014 University of Tampere, Finland"}]},{"@id":"https://cir.nii.ac.jp/crid/1380857673294983817","@type":"Researcher","foaf:name":[{"@value":"Nils-Göran Larsson"}],"jpcoar:affiliationName":[{"@value":"Department of Laboratory Medicine, Karolinska Institute, S-141 86 Stockholm, Sweden; and Institute of Medical Technology and Tampere University Hospital, FI-33014 University of Tampere, Finland"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"2005-12-06","prism:volume":"102","prism:number":"50","prism:startingPage":"17993","prism:endingPage":"17998"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.0508886102"}],"createdAt":"2005-12-07","modifiedAt":"2022-04-12","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050001202554046976","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Transmitochondrial mito-miceΔ and mtDNA mutator mice but not aged mice share the same spectrum of musculoskeletal disorders"}]},{"@id":"https://cir.nii.ac.jp/crid/1050001202559806976","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Specific mtDNA Mutations in Mouse Carcinoma Cells Suppress Their Tumor Formation via Activation of the Host Innate Immune 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