Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities
書誌事項
- 公開日
- 2019-12-20
- 権利情報
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- https://creativecommons.org/licenses/by/4.0
- https://creativecommons.org/licenses/by/4.0
- DOI
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- 10.1038/s41467-019-13694-1
- 公開者
- Springer Science and Business Media LLC
説明
<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>
収録刊行物
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- Nature Communications
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Nature Communications 10 (1), 5808-, 2019-12-20
Springer Science and Business Media LLC
