TY - JOUR
T1 - Autophagy Impairment in Muscle Induces Neuromuscular Junction Degeneration and Precocious Aging
AU - Carnio, Silvia
AU - LoVerso, Francesca
AU - Baraibar, MartinAndres
AU - Longa, Emanuela
AU - Khan, MuzamilMajid
AU - Maffei, Manuela
AU - Reischl, Markus
AU - Canepari, Monica
AU - Loefler, Stefan
AU - Kern, Helmut
AU - Blaauw, Bert
AU - Friguet, Bertrand
AU - Bottinelli, Roberto
AU - Rudolf, Rüdiger
AU - Sandri, Marco
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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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U2 - 10.1016/j.celrep.2014.07.061
DO - 10.1016/j.celrep.2014.07.061
M3 - Article
C2 - 25176656
AN - SCOPUS:84922545106
VL - 8
SP - 1509
EP - 1521
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 5
ER -