Autophagy Impairment in Muscle Induces Neuromuscular Junction Degeneration and Precocious Aging

Silvia Carnio, Francesca LoVerso, MartinAndres Baraibar, Emanuela Longa, MuzamilMajid Khan, Manuela Maffei, Markus Reischl, Monica Canepari, Stefan Loefler, Helmut Kern, Bert Blaauw, Bertrand Friguet, Roberto Bottinelli, Rüdiger Rudolf, Marco Sandri

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1509-1521
Number of pages13
JournalCell Reports
Volume8
Issue number5
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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