Journal article

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

  • Migliavacca E Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Tay SKH KTP-National University Children's Medical Institute, National University Hospital, Singapore, Singapore.
  • Patel HP Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
  • Sonntag T Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Civiletto G Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • McFarlane C Department of Molecular & Cell Biology, College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, Queensland, Australia.
  • Forrester T UWI Solutions for Developing Countries, UWI SODECO, University of West Indies, Kingston, Jamaica.
  • Barton SJ Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
  • Leow MK Singapore Institute for Clinical Sciences (A*STAR), Singapore, Singapore.
  • Antoun E Institute of Developmental Sciences, University of Southampton, Southampton, UK.
  • Charpagne A Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Seng Chong Y Singapore Institute for Clinical Sciences (A*STAR), Singapore, Singapore.
  • Descombes P Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Feng L Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • Francis-Emmanuel P UWI Solutions for Developing Countries, UWI SODECO, University of West Indies, Kingston, Jamaica.
  • Garratt ES National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
  • Giner MP Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Green CO UWI Solutions for Developing Countries, UWI SODECO, University of West Indies, Kingston, Jamaica.
  • Karaz S Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Kothandaraman N Singapore Institute for Clinical Sciences (A*STAR), Singapore, Singapore.
  • Marquis J Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Metairon S Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Moco S Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Nelson G UWI Solutions for Developing Countries, UWI SODECO, University of West Indies, Kingston, Jamaica.
  • Ngo S Liggins Institute, University of Auckland, Auckland, New Zealand.
  • Pleasants T Liggins Institute, University of Auckland, Auckland, New Zealand.
  • Raymond F Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Sayer AA Academic Geriatric Medicine, , University of Southampton, Southampton, UK.
  • Ming Sim C Singapore Institute for Clinical Sciences (A*STAR), Singapore, Singapore.
  • Slater-Jefferies J Institute of Developmental Sciences, University of Southampton, Southampton, UK.
  • Syddall HE Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
  • Fang Tan P Singapore Institute for Clinical Sciences (A*STAR), Singapore, Singapore.
  • Titcombe P Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
  • Vaz C Singapore Institute for Clinical Sciences (A*STAR), Singapore, Singapore.
  • Westbury LD Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
  • Wong G Singapore Institute for Clinical Sciences (A*STAR), Singapore, Singapore.
  • Yonghui W Singapore Institute for Clinical Sciences (A*STAR), Singapore, Singapore.
  • Cooper C Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
  • Sheppard A Liggins Institute, University of Auckland, Auckland, New Zealand.
  • Godfrey KM Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK. kmg@mrc.soton.ac.uk.
  • Lillycrop KA National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK. K.A.Lillycrop@soton.ac.uk.
  • Karnani N Singapore Institute for Clinical Sciences (A*STAR), Singapore, Singapore. neerja_karnani@sics.a-star.edu.sg.
  • Feige JN Nestle Research, EPFL Innovation Park, Lausanne, Switzerland. Jerome.feige@rd.nestle.com.
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  • 2019-12-22
Published in:
  • Nature communications. - 2019
English 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.
Language
  • English
Open access status
gold
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Persistent URL
https://sonar.ch/global/documents/212288
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