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