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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Migliavacca 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,Kothandaram

doi

10.1038/s41467-019-13694-1

subject

Has Abstract

pub_date

2019-12-20 00:00:00

pages

5808

issue

1

issn

2041-1723

pii

10.1038/s41467-019-13694-1

journal_volume

10

pub_type

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