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

Journal Publication ResearchOnline@JCU
Migliavacca, Eugenia;Tay, Stacey K.H.;Patel, Harnish P.;Sonntag, Tanja;Civiletto, Gabriele;McFarlane, Craig McFarlane;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;Wu, Yonghui;Cooper, Cyrus;Sheppard, Allan;Godfrey, Keith M.;Lillycrop, Karen;Karnani, Neerja;Feige, Jerome N.
Craig McFarlane
Abstract

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+ 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.

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Nature Communications

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10

ISBN/ISSN

2041-1723

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Pages Count

14

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Publisher

Nature Publishing Group

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DOI

10.1038/s41467-019-13694-1