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Nat Commun ; 10(1): 5808, 2019 12 20.
Article in English | MEDLINE | ID: mdl-31862890

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.


Subject(s)
Aging/physiology , Mitochondria/pathology , Muscle, Skeletal/pathology , NAD/biosynthesis , Sarcopenia/pathology , Aged , Aged, 80 and over , Biopsy , Case-Control Studies , Energy Metabolism/physiology , Humans , Jamaica , Male , Middle Aged , Mitochondria/metabolism , Muscle, Skeletal/cytology , Muscle, Skeletal/metabolism , Oxidation-Reduction , Oxidative Phosphorylation , Oxidative Stress/physiology , Proteostasis , Sarcopenia/ethnology , Singapore , United Kingdom
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