A. M. Payne and Z. Zheng contributed equally to this work.
Motor neurone targeting of IGF-1 prevents specific force decline in ageing mouse muscle
Article first published online: 4 JAN 2006
The Journal of Physiology
Volume 570, Issue 2, pages 283–294, January 2006
How to Cite
Payne, A. M., Zheng, Z., Messi, M. L., Milligan, C. E., González, E. and Delbono, O. (2006), Motor neurone targeting of IGF-1 prevents specific force decline in ageing mouse muscle. The Journal of Physiology, 570: 283–294. doi: 10.1113/jphysiol.2005.100032
- Issue published online: 4 JAN 2006
- Article first published online: 4 JAN 2006
- (Resubmitted 12 October 2005; accepted after revision 11 November 2005; first published online 17 November 2005)
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.