Denervated muscle fibers induce mitochondrial peroxide generation in neighboring innervated fibers: Role in muscle aging

Pollock, Natalie ORCID: 0000-0002-4969-5486, Staunton, Caroline A ORCID: 0000-0003-0647-3063, Vasilaki, Aphrodite ORCID: 0000-0002-5652-0895, McArdle, Anne and Jackson, Malcolm J ORCID: 0000-0003-3683-8297
(2017) Denervated muscle fibers induce mitochondrial peroxide generation in neighboring innervated fibers: Role in muscle aging. FREE RADICAL BIOLOGY AND MEDICINE, 112. pp. 84-92.

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Disruption of neuromuscular junctions and denervation of some muscle fibers occurs in ageing skeletal muscle and contribute to loss of muscle mass and function. Aging is associated with mitochondrial dysfunction and loss of redox homeostasis potentially occurs through increased mitochondrial generation of reactive oxygen species (ROS). No specific link between increased mitochondrial ROS generation and denervation has been defined in muscle ageing. To address this, we have examined the effect of experimental denervation of all fibers, or only a proportion of the fibers, in the mouse tibialis anterior (TA) muscle on muscle mitochondrial peroxide generation. Transection of the peroneal nerve of mice caused loss of pre-synaptic axons within 1–3 days with no significant morphological changes in post-synaptic structures up to 10 days post-surgery when decreased TA mass and fiber size were apparent. Mitochondria in the denervated muscle showed increased peroxide generation by 3 days post-transection. Use of electron transport chain (ETC) substrates and inhibitors of specific pathways indicated that the ETC was unlikely to contribute to increased ROS generation, but monoamine oxidase B, NADPH oxidase and phospholipase enzymes were implicated. Transection of one of the 3 branches of the peroneal nerve caused denervation of some TA muscle fibers while others retained innervation, but increased mitochondrial peroxide generation occurred in both denervated and innervated fibers. Thus the presence of recently denervated fibers leads to increased ROS generation by mitochondria in neighboring innervated fibers providing a novel explanation for the increased mitochondrial oxidative stress and damage seen with aging in skeletal muscles.

Item Type: Article
Uncontrolled Keywords: Hydrogen peroxide, Denervation, Skeletal muscle, Sarcopenia
Depositing User: Symplectic Admin
Date Deposited: 04 Aug 2017 10:34
Last Modified: 19 Jan 2023 06:58
DOI: 10.1016/j.freeradbiomed.2017.07.017
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