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Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities.
Migliavacca, Eugenia; Tay, Stacey K H; Patel, Harnish P; Sonntag, Tanja; Civiletto, Gabriele; McFarlane, Craig; Forrester, Terence; Barton, Sheila J; Leow, Melvin K; Antoun, Elie; Charpagne, Aline; Seng Chong, Yap; Descombes, Patrick; Feng, Lei; Francis-Emmanuel, Patrice; Garratt, Emma S; Giner, Maria Pilar; Green, Curtis O; Karaz, Sonia; Kothandaraman, Narasimhan; Marquis, Julien; Metairon, Sylviane; Moco, Sofia; Nelson, Gail; Ngo, Sherry; Pleasants, Tony; Raymond, Frederic; Sayer, Avan A; Ming Sim, Chu; Slater-Jefferies, Jo; Syddall, Holly E; Fang Tan, Pei; Titcombe, Philip; Vaz, Candida; Westbury, Leo D; Wong, Gerard; Yonghui, Wu; Cooper, Cyrus; Sheppard, Allan; Godfrey, Keith M; Lillycrop, Karen A; Karnani, Neerja; Feige, Jerome N.
Afiliação
  • 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; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • Sonntag T; Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
  • Civiletto G; National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
  • McFarlane C; Academic Geriatric Medicine, , University of Southampton, Southampton, UK.
  • Forrester T; Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Barton SJ; EPFL school of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland.
  • Leow MK; Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Antoun E; Department of Molecular & Cell Biology, College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, Queensland, Australia.
  • Charpagne A; UWI Solutions for Developing Countries, UWI SODECO, University of West Indies, Kingston, Jamaica.
  • Seng Chong Y; Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
  • Descombes P; Singapore Institute for Clinical Sciences (A*STAR), Singapore, Singapore.
  • Feng L; Department of Endocrinology, Tan Tock Seng Hospital, Singapore, Singapore.
  • Francis-Emmanuel P; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
  • Garratt ES; Institute of Developmental Sciences, University of Southampton, Southampton, UK.
  • Giner MP; Centre for Biological Sciences, University of Southampton, Southampton, UK.
  • Green CO; Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Karaz S; Singapore Institute for Clinical Sciences (A*STAR), Singapore, Singapore.
  • Kothandaraman N; Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • Marquis J; Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Metairon S; Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • Moco S; UWI Solutions for Developing Countries, UWI SODECO, University of West Indies, Kingston, Jamaica.
  • Nelson G; National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
  • Ngo S; Institute of Developmental Sciences, University of Southampton, Southampton, UK.
  • Pleasants T; Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Raymond F; UWI Solutions for Developing Countries, UWI SODECO, University of West Indies, Kingston, Jamaica.
  • Sayer AA; Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Ming Sim C; Singapore Institute for Clinical Sciences (A*STAR), Singapore, Singapore.
  • Slater-Jefferies J; Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Syddall HE; Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Fang Tan P; Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Titcombe P; UWI Solutions for Developing Countries, UWI SODECO, University of West Indies, Kingston, Jamaica.
  • Vaz C; Liggins Institute, University of Auckland, Auckland, New Zealand.
  • Westbury LD; Liggins Institute, University of Auckland, Auckland, New Zealand.
  • Wong G; Nestle Research, EPFL Innovation Park, Lausanne, Switzerland.
  • Yonghui W; Academic Geriatric Medicine, , University of Southampton, Southampton, UK.
  • Cooper C; AGE Research Group, Institute of Neuroscience, Faculty of Medical Sciences, Newcastle University, Newcastle, UK.
  • Sheppard A; NIHR Newcastle Biomedical Research Centre, Newcastle upon-Tyne NHS Foundation Trust and Newcastle University, Newcastle, UK.
  • Godfrey KM; Singapore Institute for Clinical Sciences (A*STAR), Singapore, Singapore.
  • Lillycrop KA; Institute of Developmental Sciences, University of Southampton, Southampton, UK.
  • Karnani N; Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
  • Feige JN; Singapore Institute for Clinical Sciences (A*STAR), Singapore, Singapore.
Nat Commun ; 10(1): 5808, 2019 12 20.
Article em En | MEDLINE | ID: mdl-31862890
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Observational_studies Limite: Aged / Aged80 / Humans / Male / Middle aged País/Região como assunto: Asia / Caribe ingles / Europa / Jamaica Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Observational_studies Limite: Aged / Aged80 / Humans / Male / Middle aged País/Região como assunto: Asia / Caribe ingles / Europa / Jamaica Idioma: En Ano de publicação: 2019 Tipo de documento: Article