Mitochondrial Oxidative Capacity and NAD Biosynthesis Are Reduced in Human Sarcopenia Across Ethnicities

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Dec 22

PMID 31862890

Citations 121

Authors

Eugenia Migliavacca

Stacey K H Tay

Harnish P Patel

Tanja Sonntag

Gabriele Civiletto

Craig McFarlane

Terence Forrester

Sheila J Barton

Melvin K Leow

Elie Antoun

Aline Charpagne

Yap Seng Chong

Patrick Descombes

Lei Feng

Patrice Francis-Emmanuel

Emma S Garratt

Maria Pilar Giner

Curtis O Green

Sonia Karaz

Narasimhan Kothandaraman

Julien Marquis

Sylviane Metairon

Sofia Moco

Gail Nelson

Sherry Ngo

Tony Pleasants

Frederic Raymond

Avan A Sayer

Chu Ming Sim

Jo Slater-Jefferies

Holly E Syddall

Pei Fang Tan

Philip Titcombe

Candida Vaz

Leo D Westbury

Gerard Wong

Wu Yonghui

Cyrus Cooper

Allan Sheppard

Keith M Godfrey

Karen A Lillycrop

Neerja Karnani

Jerome N Feige

Affiliations

Soon will be listed here.

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.

Citing Articles

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Multi-omic profiling of sarcopenia identifies disrupted branched-chain amino acid catabolism as a causal mechanism and therapeutic target.

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PrP Glycoprotein Is Indispensable for Maintenance of Skeletal Muscle Homeostasis During Aging.

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