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

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_9D3D5972CC46
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Mitochondrial oxidative capacity and NAD(+) biosynthesis are reduced in human sarcopenia across ethnicities.
Périodique
Nature communications
Auteur⸱e⸱s
Migliavacca Eugenia, Tay Stacey K. H., Patel Harnish P., Sonntag Tanja, Civiletto Gabriele, McFarlane Craig, Forrester Terence, Barton Sheila J., Leow Melvin K., Antoun Elie, Charpagne Aline, Seng Chong Yap, Descombes Patrick, Feng Lei, Francis-Emmanuel Patrice, Garratt Emma S., Giner Maria Pilar, Green Curtis O., Karaz Sonia, Kothandaraman Narasimhan, Marquis Julien, Metairon Sylviane, Moco Sofia, Nelson Gail, Ngo Sherry, Pleasants Tony, Raymond Frederic, Sayer Avan A., Ming Sim Chu, Slater-Jefferies Jo, Syddall Holly E., Fang Tan Pei, Titcombe Philip, Vaz Candida, Westbury Leo D., Wong Gerard, Yonghui Wu, Cooper Cyrus, Sheppard Allan, Godfrey Keith M., Lillycrop Karen A., Karnani Neerja, Feige Jerome N.
Statut éditorial
Publié
Date de publication
12/2019
Volume
10
Numéro
1
Pages
5808
Langue
anglais
Résumé
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-1alpha/ERRalpha 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.
Pubmed
Création de la notice
19/02/2020 12:23
Dernière modification de la notice
29/04/2021 15:31
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