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

Author

Listed:
  • Eugenia Migliavacca

    (Nestle Research, EPFL Innovation Park)

  • Stacey K. H. Tay

    (KTP-National University Children’s Medical Institute, National University Hospital
    National University of Singapore)

  • Harnish P. Patel

    (University of Southampton
    National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust
    , University of Southampton)

  • Tanja Sonntag

    (Nestle Research, EPFL Innovation Park
    Ecole Polytechnique Federale de Lausanne)

  • Gabriele Civiletto

    (Nestle Research, EPFL Innovation Park)

  • Craig McFarlane

    (James Cook University)

  • Terence Forrester

    (University of West Indies)

  • Sheila J. Barton

    (University of Southampton)

  • Melvin K. Leow

    (Singapore Institute for Clinical Sciences (A*STAR)
    Tan Tock Seng Hospital
    Nanyang Technological University)

  • Elie Antoun

    (Institute of Developmental Sciences, University of Southampton
    University of Southampton)

  • Aline Charpagne

    (Nestle Research, EPFL Innovation Park)

  • Yap Seng Chong

    (Singapore Institute for Clinical Sciences (A*STAR)
    National University of Singapore)

  • Patrick Descombes

    (Nestle Research, EPFL Innovation Park)

  • Lei Feng

    (National University of Singapore)

  • Patrice Francis-Emmanuel

    (University of West Indies)

  • Emma S. Garratt

    (National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust
    Institute of Developmental Sciences, University of Southampton)

  • Maria Pilar Giner

    (Nestle Research, EPFL Innovation Park)

  • Curtis O. Green

    (University of West Indies)

  • Sonia Karaz

    (Nestle Research, EPFL Innovation Park)

  • Narasimhan Kothandaraman

    (Singapore Institute for Clinical Sciences (A*STAR))

  • Julien Marquis

    (Nestle Research, EPFL Innovation Park)

  • Sylviane Metairon

    (Nestle Research, EPFL Innovation Park)

  • Sofia Moco

    (Nestle Research, EPFL Innovation Park)

  • Gail Nelson

    (University of West Indies)

  • Sherry Ngo

    (Liggins Institute, University of Auckland)

  • Tony Pleasants

    (Liggins Institute, University of Auckland)

  • Frederic Raymond

    (Nestle Research, EPFL Innovation Park)

  • Avan A. Sayer

    (, University of Southampton
    Institute of Neuroscience, Faculty of Medical Sciences, Newcastle University
    Newcastle upon-Tyne NHS Foundation Trust and Newcastle University)

  • Chu Ming Sim

    (Singapore Institute for Clinical Sciences (A*STAR))

  • Jo Slater-Jefferies

    (Institute of Developmental Sciences, University of Southampton)

  • Holly E. Syddall

    (University of Southampton)

  • Pei Fang Tan

    (Singapore Institute for Clinical Sciences (A*STAR))

  • Philip Titcombe

    (University of Southampton)

  • Candida Vaz

    (Singapore Institute for Clinical Sciences (A*STAR))

  • Leo D. Westbury

    (University of Southampton)

  • Gerard Wong

    (Singapore Institute for Clinical Sciences (A*STAR))

  • Wu Yonghui

    (Singapore Institute for Clinical Sciences (A*STAR))

  • Cyrus Cooper

    (University of Southampton
    National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust
    National Institute for Health Research Musculoskeletal Biomedical Research Unit, University of Oxford)

  • Allan Sheppard

    (Liggins Institute, University of Auckland)

  • Keith M. Godfrey

    (University of Southampton
    National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust
    Institute of Developmental Sciences, University of Southampton)

  • Karen A. Lillycrop

    (National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust
    Institute of Developmental Sciences, University of Southampton
    University of Southampton)

  • Neerja Karnani

    (Singapore Institute for Clinical Sciences (A*STAR)
    National University of Singapore)

  • Jerome N. Feige

    (Nestle Research, EPFL Innovation Park
    Ecole Polytechnique Federale de Lausanne)

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.

Suggested Citation

  • 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, 2019. "Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13694-1
    DOI: 10.1038/s41467-019-13694-1
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    Cited by:

    1. Marc Beltrà & Noora Pöllänen & Claudia Fornelli & Kialiina Tonttila & Myriam Y. Hsu & Sandra Zampieri & Lucia Moletta & Samantha Corrà & Paolo E. Porporato & Riikka Kivelä & Carlo Viscomi & Marco Sand, 2023. "NAD+ repletion with niacin counteracts cancer cachexia," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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