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Autophagy Impairment in Muscle Induces Neuromuscular Junction Degeneration and Precocious Aging

The cellular basis of age-related tissue deterioration remains largely obscure. The ability to activate compensatory mechanisms in response to environmental stress is an important factor for survival and maintenance of cellular functions. Autophagy is activated both under short and prolonged stress...

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Autores principales: Carnio, Silvia, LoVerso, Francesca, Baraibar, Martin Andres, Longa, Emanuela, Khan, Muzamil Majid, Maffei, Manuela, Reischl, Markus, Canepari, Monica, Loefler, Stefan, Kern, Helmut, Blaauw, Bert, Friguet, Bertrand, Bottinelli, Roberto, Rudolf, Rüdiger, Sandri, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534571/
https://www.ncbi.nlm.nih.gov/pubmed/25176656
http://dx.doi.org/10.1016/j.celrep.2014.07.061
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author Carnio, Silvia
LoVerso, Francesca
Baraibar, Martin Andres
Longa, Emanuela
Khan, Muzamil Majid
Maffei, Manuela
Reischl, Markus
Canepari, Monica
Loefler, Stefan
Kern, Helmut
Blaauw, Bert
Friguet, Bertrand
Bottinelli, Roberto
Rudolf, Rüdiger
Sandri, Marco
author_facet Carnio, Silvia
LoVerso, Francesca
Baraibar, Martin Andres
Longa, Emanuela
Khan, Muzamil Majid
Maffei, Manuela
Reischl, Markus
Canepari, Monica
Loefler, Stefan
Kern, Helmut
Blaauw, Bert
Friguet, Bertrand
Bottinelli, Roberto
Rudolf, Rüdiger
Sandri, Marco
author_sort Carnio, Silvia
collection PubMed
description The cellular basis of age-related tissue deterioration remains largely obscure. The ability to activate compensatory mechanisms in response to environmental stress is an important factor for survival and maintenance of cellular functions. Autophagy is activated both under short and prolonged stress and is required to clear the cell of dysfunctional organelles and altered proteins. We report that specific autophagy inhibition in muscle has a major impact on neuromuscular synaptic function and, consequently, on muscle strength, ultimately affecting the lifespan of animals. Inhibition of autophagy also exacerbates aging phenotypes in muscle, such as mitochondrial dysfunction, oxidative stress, and profound weakness. Mitochondrial dysfunction and oxidative stress directly affect acto-myosin interaction and force generation but show a limited effect on stability of neuromuscular synapses. These results demonstrate that age-related deterioration of synaptic structure and function is exacerbated by defective autophagy.
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spelling pubmed-45345712015-08-13 Autophagy Impairment in Muscle Induces Neuromuscular Junction Degeneration and Precocious Aging Carnio, Silvia LoVerso, Francesca Baraibar, Martin Andres Longa, Emanuela Khan, Muzamil Majid Maffei, Manuela Reischl, Markus Canepari, Monica Loefler, Stefan Kern, Helmut Blaauw, Bert Friguet, Bertrand Bottinelli, Roberto Rudolf, Rüdiger Sandri, Marco Cell Rep Article The cellular basis of age-related tissue deterioration remains largely obscure. The ability to activate compensatory mechanisms in response to environmental stress is an important factor for survival and maintenance of cellular functions. Autophagy is activated both under short and prolonged stress and is required to clear the cell of dysfunctional organelles and altered proteins. We report that specific autophagy inhibition in muscle has a major impact on neuromuscular synaptic function and, consequently, on muscle strength, ultimately affecting the lifespan of animals. Inhibition of autophagy also exacerbates aging phenotypes in muscle, such as mitochondrial dysfunction, oxidative stress, and profound weakness. Mitochondrial dysfunction and oxidative stress directly affect acto-myosin interaction and force generation but show a limited effect on stability of neuromuscular synapses. These results demonstrate that age-related deterioration of synaptic structure and function is exacerbated by defective autophagy. Cell Press 2014-08-28 /pmc/articles/PMC4534571/ /pubmed/25176656 http://dx.doi.org/10.1016/j.celrep.2014.07.061 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Article
Carnio, Silvia
LoVerso, Francesca
Baraibar, Martin Andres
Longa, Emanuela
Khan, Muzamil Majid
Maffei, Manuela
Reischl, Markus
Canepari, Monica
Loefler, Stefan
Kern, Helmut
Blaauw, Bert
Friguet, Bertrand
Bottinelli, Roberto
Rudolf, Rüdiger
Sandri, Marco
Autophagy Impairment in Muscle Induces Neuromuscular Junction Degeneration and Precocious Aging
title Autophagy Impairment in Muscle Induces Neuromuscular Junction Degeneration and Precocious Aging
title_full Autophagy Impairment in Muscle Induces Neuromuscular Junction Degeneration and Precocious Aging
title_fullStr Autophagy Impairment in Muscle Induces Neuromuscular Junction Degeneration and Precocious Aging
title_full_unstemmed Autophagy Impairment in Muscle Induces Neuromuscular Junction Degeneration and Precocious Aging
title_short Autophagy Impairment in Muscle Induces Neuromuscular Junction Degeneration and Precocious Aging
title_sort autophagy impairment in muscle induces neuromuscular junction degeneration and precocious aging
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534571/
https://www.ncbi.nlm.nih.gov/pubmed/25176656
http://dx.doi.org/10.1016/j.celrep.2014.07.061
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