Older mice show decreased regeneration of neuromuscular junctions following lengthening contraction-induced injury

Paul, Thomas A, Macpherson, Peter C, Janetzke, Tara L, Davis, Carol S, Jackson, Malcolm J ORCID: 0000-0003-3683-8297, McArdle, Anne and Brooks, Susan V
(2023) Older mice show decreased regeneration of neuromuscular junctions following lengthening contraction-induced injury. GEROSCIENCE, 45 (3). pp. 1899-1912.

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Progressive muscle atrophy and loss of muscle strength associated with old age have been well documented. Although age-associated impairments in skeletal muscle regeneration following injury have been demonstrated, less is known about whether aging impacts the regenerative response of neuromuscular junctions (NMJ) following contraction-induced injury. Reduced ability of NMJs to regenerate could lead to increased numbers of denervated muscle fibers and therefore play a contributing role to age-related sarcopenia. To investigate the relationship between age and NMJ regeneration following injury, extensor digitorum longus (EDL) muscles of middle-aged (18-19 months) and old mice (27-28 months) were subjected to a protocol of lengthening contractions (LC) that resulted in an acute force deficit of ~55% as well as functional and histological evidence of a similar magnitude of injury 3 days post LCs that was not different between age groups. After 28 days, the architecture and innervation of the NMJs were evaluated. The numbers of fragmented endplates increased and of fully innervated NMJs decreased post-injury for the muscle of both middle-aged and old mice and for contralateral uninjured muscles of old compared with uninjured muscles of middle-aged controls. Thus, the diminished ability of the skeletal muscle of old mice to recover following injury may be due in part to an age-related decrease in the ability to regenerate NMJs in injured muscles. The impaired ability to regenerate NMJs may be a triggering factor for degenerative changes at the NMJ contributing to muscle fiber weakness and loss in old age.

Item Type: Article
Uncontrolled Keywords: Aging, Injury, Innervation, Lengthening contractions, Muscle, Neuromuscular junction, Regeneration, Sarcopenia
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 26 Sep 2023 08:36
Last Modified: 26 Sep 2023 08:36
DOI: 10.1007/s11357-023-00774-w
Open Access URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10400...
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3170319