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

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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925228/
https://www.ncbi.nlm.nih.gov/pubmed/31862890
http://dx.doi.org/10.1038/s41467-019-13694-1
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author 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.
author_facet 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.
author_sort Migliavacca, Eugenia
collection PubMed
description 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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spelling pubmed-69252282019-12-22 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. Nat Commun Article 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. Nature Publishing Group UK 2019-12-20 /pmc/articles/PMC6925228/ /pubmed/31862890 http://dx.doi.org/10.1038/s41467-019-13694-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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.
Mitochondrial oxidative capacity and NAD(+) biosynthesis are reduced in human sarcopenia across ethnicities
title Mitochondrial oxidative capacity and NAD(+) biosynthesis are reduced in human sarcopenia across ethnicities
title_full Mitochondrial oxidative capacity and NAD(+) biosynthesis are reduced in human sarcopenia across ethnicities
title_fullStr Mitochondrial oxidative capacity and NAD(+) biosynthesis are reduced in human sarcopenia across ethnicities
title_full_unstemmed Mitochondrial oxidative capacity and NAD(+) biosynthesis are reduced in human sarcopenia across ethnicities
title_short Mitochondrial oxidative capacity and NAD(+) biosynthesis are reduced in human sarcopenia across ethnicities
title_sort mitochondrial oxidative capacity and nad(+) biosynthesis are reduced in human sarcopenia across ethnicities
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925228/
https://www.ncbi.nlm.nih.gov/pubmed/31862890
http://dx.doi.org/10.1038/s41467-019-13694-1
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