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This Article Full Text Full Text (PDF) All Versions of this Article: 570/2/283    most recent jphysiol.2005.100032v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Payne, A. M. Articles by Delbono, O. Search for Related Content PubMed PubMed Citation Articles by Payne, A. M. Articles by Delbono, O. Related Collections Cellular

¹ Department of Physiology and Pharmacology
² Department of Neurobiology & Anatomy
³ Department of Internal Medicine, Section on Gerontology
⁴ Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA

IGF-1 is a potent growth factor for both motor neurones and skeletal muscle. Muscle IGF-1 is known to provide target-derived trophic effects on motor neurones. Therefore, IGF-1 overexpression in muscle is effective in delaying or preventing deleterious effects of ageing in both tissues. Since age-related decline in muscle function stems partly from motor neurone loss, a tetanus toxin fragment-C (TTC) fusion protein was created to target IGF-1 to motor neurones. IGF-1–TTC retains IGF-1 activity as indicated by [³H]thymidine incorporation into L6 myoblasts. Spinal cord motor neurones effectively bound and internalized the IGF-1–TTC in vitro. Similarly, IGF-1–TTC injected into skeletal muscles was taken up and retrogradely transported to the spinal cord in vivo, a process prevented by denervation of injected muscles. Three monthly IGF-1–TTC injections into muscles of ageing mice did not increase muscle weight or muscle fibre size, but significantly increased single fibre specific force over aged controls injected with saline, IGF-1, or TTC. None of the injections changed muscle fibre type composition, but neuromuscular junction post-terminals were larger and more complex in muscle fibres injected with IGF-1–TTC, compared to the other groups, suggesting preservation of muscle fibre innervation. This work demonstrates that induced overexpression of IGF-1 in spinal cord motor neurones of ageing mice prevents muscle fibre specific force decline, a hallmark of ageing skeletal muscle.

(Received 12 October 2005; accepted after revision 11 November 2005; first published online 17 November 2005)
Corresponding author O. Delbono: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, 1 Medical Center Boulevard, Winston-Salem, NC 27157, USA. Email: odelbono{at}wfubmc.edu

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