Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities

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dc.citation.issue1
dc.citation.volume10
dc.contributor.authorMigliavacca E
dc.contributor.authorTay SKH
dc.contributor.authorPatel HP
dc.contributor.authorSonntag T
dc.contributor.authorCiviletto G
dc.contributor.authorMcFarlane C
dc.contributor.authorForrester T
dc.contributor.authorBarton SJ
dc.contributor.authorLeow MK
dc.contributor.authorAntoun E
dc.contributor.authorCharpagne A
dc.contributor.authorSeng Chong Y
dc.contributor.authorDescombes P
dc.contributor.authorFeng L
dc.contributor.authorFrancis-Emmanuel P
dc.contributor.authorGarratt ES
dc.contributor.authorGiner MP
dc.contributor.authorGreen CO
dc.contributor.authorKaraz S
dc.contributor.authorKothandaraman N
dc.contributor.authorMarquis J
dc.contributor.authorMetairon S
dc.contributor.authorMoco S
dc.contributor.authorNelson G
dc.contributor.authorNgo S
dc.contributor.authorPleasants T
dc.contributor.authorRaymond F
dc.contributor.authorSayer AA
dc.contributor.authorMing Sim C
dc.contributor.authorSlater-Jefferies J
dc.contributor.authorSyddall HE
dc.contributor.authorFang Tan P
dc.contributor.authorTitcombe P
dc.contributor.authorVaz C
dc.contributor.authorWestbury LD
dc.contributor.authorWong G
dc.contributor.authorYonghui W
dc.contributor.authorCooper C
dc.contributor.authorSheppard A
dc.contributor.authorGodfrey KM
dc.contributor.authorLillycrop KA
dc.contributor.authorKarnani N
dc.contributor.authorFeige JN
dc.coverage.spatialEngland
dc.date.accessioned2024-10-10T22:00:10Z
dc.date.available2024-10-10T22:00:10Z
dc.date.issued2019-12-20
dc.description.abstractThe 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+ levels through perturbed NAD+ 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.
dc.description.confidentialfalse
dc.edition.edition2019
dc.format.pagination5808-
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/31862890
dc.identifier.citationMigliavacca E, Tay SKH, Patel HP, Sonntag T, Civiletto G, McFarlane C, Forrester T, Barton SJ, Leow MK, Antoun E, Charpagne A, Seng Chong Y, Descombes P, Feng L, Francis-Emmanuel P, Garratt ES, Giner MP, Green CO, Karaz S, Kothandaraman N, Marquis J, Metairon S, Moco S, Nelson G, Ngo S, Pleasants T, Raymond F, Sayer AA, Ming Sim C, Slater-Jefferies J, Syddall HE, Fang Tan P, Titcombe P, Vaz C, Westbury LD, Wong G, Yonghui W, Cooper C, Sheppard A, Godfrey KM, Lillycrop KA, Karnani N, Feige JN. (2019). Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities.. Nat Commun. 10. 1. (pp. 5808-).
dc.identifier.doi10.1038/s41467-019-13694-1
dc.identifier.eissn2041-1723
dc.identifier.elements-typejournal-article
dc.identifier.issn2041-1723
dc.identifier.number5808
dc.identifier.pii10.1038/s41467-019-13694-1
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/71684
dc.languageeng
dc.publisherSpringer Nature Limited
dc.publisher.urihttps://www.nature.com/articles/s41467-019-13694-1
dc.relation.isPartOfNat Commun
dc.rights(c) 2019 The Author/s
dc.rightsCC BY 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectAging
dc.subjectBiopsy
dc.subjectCase-Control Studies
dc.subjectEnergy Metabolism
dc.subjectHumans
dc.subjectJamaica
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectMitochondria
dc.subjectMuscle, Skeletal
dc.subjectNAD
dc.subjectOxidation-Reduction
dc.subjectOxidative Phosphorylation
dc.subjectOxidative Stress
dc.subjectProteostasis
dc.subjectSarcopenia
dc.subjectSingapore
dc.subjectUnited Kingdom
dc.titleMitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities
dc.typeJournal article
pubs.elements-id428895
pubs.organisational-groupOther
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