NDLI: Elderly mouse skeletal muscle fibres have a diminished capacity to upregulate NCAM production in response to denervation

Content Provider	Springer Nature Link
Author	Gillon, Ashley Sheard, Philip
Copyright Year	2015
Abstract	Sarcopenia is a major contributor to the loss of independence and deteriorating quality of life in elderly individuals, it manifests as a decline in skeletal muscle mass and strength beyond the age of 65. Muscle fibre atrophy is a major contributor to sarcopenia and the most severely atrophic fibres are commonly found in elderly muscles to have permanently lost their motor nerve input. By contrast with elderly fibres, when fibres in young animals lose their motor input they normally mount a response to induce restoration of nerve contact, and this is mediated in part by upregulated expression of the nerve cell adhesion molecule (NCAM). Therefore, skeletal muscles appear to progressively lose their ability to become reinnervated, and here we have investigated whether this decline occurs via loss of the muscle’s ability to upregulate NCAM in response to denervation. We performed partial denervation (by peripheral nerve crush) of the extensor digitorum longus muscle of the lower limb in both young and elderly mice. We used immunohistochemistry to compare relative NCAM levels at denervated and control innervated muscle fibres, focused on measurements at neuromuscular junctional, extra-junctional and cytoplasmic locations. Muscle fibres in young animals responded to denervation with significant (32.9 %) increases in unpolysialylated NCAM at extra-junctional locations, but with no change in polysialylated NCAM. The same partial denervation protocol applied to elderly animals resulted in no significant change in either polysialylated or unpolysialylated NCAM at junctional, extra-junctional or cytoplasmic locations, therefore muscle fibres in young mice upregulated NCAM in response to denervation but fibres in elderly mice failed to do so. Elevation of NCAM levels is likely to be an important component of the muscle fibre’s ability to attract or reattract a neural input, so we conclude that the presence of increasing numbers of long-term denervated fibres in elderly muscles is due, at least in part, to the fibre’s declining ability to mount a normal response to loss of motor input.
Starting Page	811
Ending Page	823
Page Count	13
File Format	PDF
ISSN	13895729
Journal	Biogerontology
Volume Number	16
Issue Number	6
e-ISSN	15736768
Language	English
Publisher	Springer Netherlands
Publisher Date	2015-09-18
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Aging muscle NCAM Sarcopenia Denervation Re-innervation Cell Biology Geriatrics/Gerontology Developmental Biology
Content Type	Text
Resource Type	Article
Subject	Aging Gerontology Geriatrics and Gerontology

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