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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

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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Verlagsausgabe §
DOI: 10.5445/IR/1000049203
Veröffentlicht am 21.03.2018
DOI: 10.1016/j.celrep.2014.07.061
Zitationen: 196
Zitationen: 225
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Angewandte Informatik (IAI)
Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2014
Sprache Englisch
Identifikator ISSN: 2211-1247
KITopen-ID: 1000049203
HGF-Programm 47.01.01 (POF II, LK 01) Biologische Schlüselmoleküle ITG
Erschienen in Cell Reports
Verlag Cell Press
Band 8
Heft 5
Seiten 1509-1521
Nachgewiesen in Scopus
Web of Science
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