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Article Dans Une Revue Cell Reports Année : 2014

Autophagy Impairment in Muscle Induces Neuromuscular Junction Degeneration and Precocious Aging

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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 auto-phagy 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 neuro-muscular synapses. These results demonstrate that age-related deterioration of synaptic structure and function is exacerbated by defective autophagy.
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hal-01311635 , version 1 (04-05-2016)

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Silvia Carnio, Francesca Loverso, Martin Andres Baraibar, Emanuela Longa, Muzamil Majid Khan, et al.. Autophagy Impairment in Muscle Induces Neuromuscular Junction Degeneration and Precocious Aging. Cell Reports, 2014, 8 (5), pp.1509-1521. ⟨10.1016/j.celrep.2014.07.061⟩. ⟨hal-01311635⟩
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