{"@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/1360013172522817536.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1038/s41467-019-13694-1"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/s41467-019-13694-1.pdf"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/s41467-019-13694-1"}}],"dc:title":[{"@value":"Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title><jats:p>The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD<jats:sup>+</jats:sup> levels through perturbed NAD<jats:sup>+</jats:sup> biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380013172522817561","@type":"Researcher","foaf:name":[{"@value":"Eugenia Migliavacca"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817416","@type":"Researcher","foaf:name":[{"@value":"Stacey K. H. Tay"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817543","@type":"Researcher","foaf:name":[{"@value":"Harnish P. Patel"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817560","@type":"Researcher","foaf:name":[{"@value":"Tanja Sonntag"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817412","@type":"Researcher","foaf:name":[{"@value":"Gabriele Civiletto"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817540","@type":"Researcher","foaf:name":[{"@value":"Craig McFarlane"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817549","@type":"Researcher","foaf:name":[{"@value":"Terence Forrester"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817555","@type":"Researcher","foaf:name":[{"@value":"Sheila J. Barton"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817413","@type":"Researcher","foaf:name":[{"@value":"Melvin K. Leow"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817559","@type":"Researcher","foaf:name":[{"@value":"Elie Antoun"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817409","@type":"Researcher","foaf:name":[{"@value":"Aline Charpagne"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817537","@type":"Researcher","foaf:name":[{"@value":"Yap Seng Chong"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817553","@type":"Researcher","foaf:name":[{"@value":"Patrick Descombes"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817552","@type":"Researcher","foaf:name":[{"@value":"Lei Feng"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817411","@type":"Researcher","foaf:name":[{"@value":"Patrice Francis-Emmanuel"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817563","@type":"Researcher","foaf:name":[{"@value":"Emma S. Garratt"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817568","@type":"Researcher","foaf:name":[{"@value":"Maria Pilar Giner"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817541","@type":"Researcher","foaf:name":[{"@value":"Curtis O. Green"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817562","@type":"Researcher","foaf:name":[{"@value":"Sonia Karaz"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817564","@type":"Researcher","foaf:name":[{"@value":"Narasimhan Kothandaraman"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817551","@type":"Researcher","foaf:name":[{"@value":"Julien Marquis"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817558","@type":"Researcher","foaf:name":[{"@value":"Sylviane Metairon"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817566","@type":"Researcher","foaf:name":[{"@value":"Sofia Moco"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817539","@type":"Researcher","foaf:name":[{"@value":"Gail Nelson"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817548","@type":"Researcher","foaf:name":[{"@value":"Sherry Ngo"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817544","@type":"Researcher","foaf:name":[{"@value":"Tony Pleasants"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817417","@type":"Researcher","foaf:name":[{"@value":"Frederic Raymond"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817547","@type":"Researcher","foaf:name":[{"@value":"Avan A. Sayer"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817408","@type":"Researcher","foaf:name":[{"@value":"Chu Ming Sim"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817554","@type":"Researcher","foaf:name":[{"@value":"Jo Slater-Jefferies"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817556","@type":"Researcher","foaf:name":[{"@value":"Holly E. Syddall"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817565","@type":"Researcher","foaf:name":[{"@value":"Pei Fang Tan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817557","@type":"Researcher","foaf:name":[{"@value":"Philip Titcombe"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817567","@type":"Researcher","foaf:name":[{"@value":"Candida Vaz"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817538","@type":"Researcher","foaf:name":[{"@value":"Leo D. Westbury"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817546","@type":"Researcher","foaf:name":[{"@value":"Gerard Wong"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817410","@type":"Researcher","foaf:name":[{"@value":"Wu Yonghui"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817545","@type":"Researcher","foaf:name":[{"@value":"Cyrus Cooper"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817536","@type":"Researcher","foaf:name":[{"@value":"Allan Sheppard"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817550","@type":"Researcher","foaf:name":[{"@value":"Keith M. Godfrey"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817415","@type":"Researcher","foaf:name":[{"@value":"Karen A. Lillycrop"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817414","@type":"Researcher","foaf:name":[{"@value":"Neerja Karnani"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013172522817542","@type":"Researcher","foaf:name":[{"@value":"Jerome N. Feige"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"20411723"}],"prism:publicationName":[{"@value":"Nature Communications"}],"dc:publisher":[{"@value":"Springer Science and Business Media LLC"}],"prism:publicationDate":"2019-12-20","prism:volume":"10","prism:number":"1","prism:startingPage":"5808"},"reviewed":"false","dc:rights":["https://creativecommons.org/licenses/by/4.0","https://creativecommons.org/licenses/by/4.0"],"url":[{"@id":"https://www.nature.com/articles/s41467-019-13694-1.pdf"},{"@id":"https://www.nature.com/articles/s41467-019-13694-1"}],"createdAt":"2019-12-20","modifiedAt":"2022-12-17","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050294807656490496","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Reduced uremic metabolites are prominent feature of sarcopenia, distinct from antioxidative markers for frailty"}]},{"@id":"https://cir.nii.ac.jp/crid/1360294643863429632","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Role of muscle stem cells in sarcopenia"}]},{"@id":"https://cir.nii.ac.jp/crid/1360857593649100032","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Identification of a KLF5-dependent program and drug development for skeletal muscle atrophy"}]},{"@id":"https://cir.nii.ac.jp/crid/1360861288383835136","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Effect of Long-Term Supplementation with Acetic Acid on the Skeletal Muscle of Aging Sprague Dawley Rats"}]},{"@id":"https://cir.nii.ac.jp/crid/1360861707372297728","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Resveratrol, a SIRT1 activator, attenuates aging-associated alterations in skeletal muscle and heart in mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360869854354541056","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Dnmt3a overexpression disrupts skeletal muscle homeostasis, promotes an aging-like phenotype, and reduces metabolic elasticity"}]},{"@id":"https://cir.nii.ac.jp/crid/1360869855137564416","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Aging and putative frailty biomarkers are altered by spaceflight"}]},{"@id":"https://cir.nii.ac.jp/crid/1390025639960787072","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Beta-nicotinamide mononucleotide attenuates creatine kinase release in Duchenne muscular dystrophy model rats"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1038/s41467-019-13694-1"},{"@type":"CROSSREF","@value":"10.18632/aging.203498_references_DOI_S8l0RfTQaXngBfzhah2zneMfLSX"},{"@type":"CROSSREF","@value":"10.1292/jvms.25-0258_references_DOI_S8l0RfTQaXngBfzhah2zneMfLSX"},{"@type":"CROSSREF","@value":"10.1016/b978-0-12-822146-4.00009-0_references_DOI_S8l0RfTQaXngBfzhah2zneMfLSX"},{"@type":"CROSSREF","@value":"10.1073/pnas.2102895118_references_DOI_S8l0RfTQaXngBfzhah2zneMfLSX"},{"@type":"CROSSREF","@value":"10.3390/ijms23094691_references_DOI_S8l0RfTQaXngBfzhah2zneMfLSX"},{"@type":"CROSSREF","@value":"10.1016/j.jphs.2023.04.001_references_DOI_S8l0RfTQaXngBfzhah2zneMfLSX"},{"@type":"CROSSREF","@value":"10.1016/j.isci.2025.112144_references_DOI_S8l0RfTQaXngBfzhah2zneMfLSX"},{"@type":"CROSSREF","@value":"10.1038/s41598-024-57948-5_references_DOI_S8l0RfTQaXngBfzhah2zneMfLSX"}]}