Migliavacca ETay SKHPatel HPSonntag TCiviletto GMcFarlane CForrester TBarton SJLeow MKAntoun ECharpagne ASeng Chong YDescombes PFeng LFrancis-Emmanuel PGarratt ESGiner MPGreen COKaraz SKothandaraman NMarquis JMetairon SMoco SNelson GNgo SPleasants TRaymond FSayer AAMing Sim CSlater-Jefferies JSyddall HEFang Tan PTitcombe PVaz CWestbury LDWong GYonghui WCooper CSheppard AGodfrey KMLillycrop KAKarnani NFeige JN2024-10-102024-10-102019-12-20Migliavacca 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-).2041-1723https://mro.massey.ac.nz/handle/10179/71684The 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.(c) 2019 The Author/sCC BY 4.0https://creativecommons.org/licenses/by/4.0/AgedAged, 80 and overAgingBiopsyCase-Control StudiesEnergy MetabolismHumansJamaicaMaleMiddle AgedMitochondriaMuscle, SkeletalNADOxidation-ReductionOxidative PhosphorylationOxidative StressProteostasisSarcopeniaSingaporeUnited KingdomJournal article10.1038/s41467-019-13694-12041-1723journal-article5808-https://www.ncbi.nlm.nih.gov/pubmed/31862890580810.1038/s41467-019-13694-1