{"@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/1360021390748839552.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1186/s41232-019-0096-y"}},{"identifier":{"@type":"URI","@value":"http://link.springer.com/content/pdf/10.1186/s41232-019-0096-y.pdf"}},{"identifier":{"@type":"URI","@value":"http://link.springer.com/article/10.1186/s41232-019-0096-y/fulltext.html"}},{"identifier":{"@type":"PMID","@value":"31057688"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Age-related dysfunction of the DNA damage response in intestinal stem cells"}],"description":[{"notation":[{"@value":"Senescence increases the risks of inflammatory bowel diseases and colon cancer. Intestinal stem cells (ISCs) in crypts differentiate into epithelial cells and thereby maintain intestinal homeostasis. However, the influence of aging on the functions of ISCs is largely unknown. The mutation rate is highest in the small and large intestines. Numerous types of naturally occurring DNA damage are removed by the DNA damage response (DDR). This response induces DNA repair and apoptosis; therefore, its dysregulation leads to accumulation of damaged DNA and consequently cellular dysfunctions, including tumorigenesis. This study investigated whether aging affects the DDR in mouse ISCs.Young (2-3-month-old) and old ( 19-month-old) Lgr5-EGFP-IRES-creERT2 mice were irradiated. The DDR in Lgr5-positive ISCs was compared between these mice by immunohistochemical analyses.Induction of DDR marker proteins (phosphorylated ATR and 53BP1), inflammatory factors (phosphorylated NF-κB and interleukin-6), and a mitochondrial biogenesis-associated gene (peroxisome proliferator-activated receptor-γ coactivator 1α) was lower in old ISCs than in young ISCs in vivo.The competence of the DDR in ISCs declines with age in vivo."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380021390748839441","@type":"Researcher","foaf:name":[{"@value":"Koichiro Watanabe"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390748839562","@type":"Researcher","foaf:name":[{"@value":"Yasuaki Ikuno"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390748839431","@type":"Researcher","foaf:name":[{"@value":"Yumi Kakeya"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390748839439","@type":"Researcher","foaf:name":[{"@value":"Shinsuke Ikeno"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390748839577","@type":"Researcher","foaf:name":[{"@value":"Hitomi Taniura"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390748839443","@type":"Researcher","foaf:name":[{"@value":"Masayoshi Kurono"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390748839579","@type":"Researcher","foaf:name":[{"@value":"Keito Minemori"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390748839554","@type":"Researcher","foaf:name":[{"@value":"Yu Katsuyama"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021390748839564","@type":"Researcher","foaf:name":[{"@value":"Hayato Naka-Kaneda"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"18808190"}],"prism:publicationName":[{"@value":"Inflammation and Regeneration"}],"dc:publisher":[{"@value":"Springer Science and Business Media LLC"}],"prism:publicationDate":"2019-04-26","prism:volume":"39","prism:number":"1"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["http://creativecommons.org/licenses/by/4.0/","http://creativecommons.org/licenses/by/4.0/"],"url":[{"@id":"http://link.springer.com/content/pdf/10.1186/s41232-019-0096-y.pdf"},{"@id":"http://link.springer.com/article/10.1186/s41232-019-0096-y/fulltext.html"}],"createdAt":"2019-04-25","modifiedAt":"2020-05-15","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Aging","dc:title":"Aging"},{"@id":"https://cir.nii.ac.jp/all?q=Pathology","dc:title":"Pathology"},{"@id":"https://cir.nii.ac.jp/all?q=RB1-214","dc:title":"RB1-214"},{"@id":"https://cir.nii.ac.jp/all?q=Intestinal%20stem%20cell","dc:title":"Intestinal stem cell"},{"@id":"https://cir.nii.ac.jp/all?q=DNA%20damage%20response","dc:title":"DNA damage response"},{"@id":"https://cir.nii.ac.jp/all?q=Research%20Article","dc:title":"Research Article"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040282256890932224","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"16K08602"},{"@type":"JGN","@value":"JP16K08602"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16K08602/"}],"notation":[{"@language":"ja","@value":"加齢による組織恒常性の破綻におけるmicroRNAが果たす役割の解明"},{"@language":"en","@value":"Roles of microRNA in age-related disruption of tissue homeostasis"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360001113981744512","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Transcriptional regulatory circuits controlling mitochondrial biogenesis and function"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011145983242368","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Emerging role of NF-κB signaling in the induction of senescence-associated secretory phenotype 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