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Updated: Jul 18, 2026
Preparation and Culture of Myogenic Precursor Cells/Primary Myoblasts from Skeletal Muscle of Adult and Aged Humans
Published on: February 16, 2017
Motor neuron targeting of IGF-1 attenuates age-related external Ca2+-dependent skeletal muscle contraction in
Anthony M Payne1, María Laura Messi, Zhenlin Zheng
1Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Abstract:
A population of fast muscle fibers from aging mice is dependent on external Ca(2+) to maintain tetanic force during repeated contractions. We hypothesized that age-related denervation in muscle fibers plays a role in initiating this contractile deficit, and that prevention of denervation by IGF-1 overexpression would prevent external Ca(2+)-dependent contraction in aging mice. IGF-1 overexpression in skeletal muscle prevents age-related denervation, and prevented external Ca(2+)-dependent contraction in this work. To determine if the effects of IGF-1 overexpression are on muscle or nerve, aging mice were injected with a tetanus toxin fragment-C (TTC) fusion protein that targets IGF-1 to spinal cord motor neurons. This treatment prevented external Ca(2+)-dependent contraction. We also show evidence that injections of the IGF-1-TTC fusion protein prevent age-related alterations to the nerve terminals at the neuromuscular junctions. We conclude that the slow age-related denervation of fast muscle fibers underlies dependence on external Ca(2+) to maintain tetanic force in a population of muscle fibers from senescent mice.
Insights
Aging fast muscle fibers lose force due to denervation, requiring external calcium. Insulin-like Growth Factor-1 (IGF-1) prevents this age-related denervation and calcium dependence, preserving muscle function.
Area of Science:
- Muscle physiology
- Neuroscience
- Aging research
Background:
- Aging muscle fibers exhibit reduced tetanic force during repeated contractions, showing a dependence on external calcium (Ca2+).
- Age-related denervation of muscle fibers is a potential cause for this contractile deficit.
Purpose of the Study:
- To investigate the role of age-related denervation in muscle fiber contractile deficits.
- To determine if Insulin-like Growth Factor-1 (IGF-1) overexpression can prevent denervation and subsequent calcium dependence in aging muscle.
Main Methods:
- Overexpression of IGF-1 in skeletal muscle of aging mice.
- Injection of tetanus toxin fragment-C (TTC) fusion protein targeting IGF-1 to spinal cord motor neurons.
- Assessment of tetanic force maintenance and neuromuscular junction integrity.
Main Results:
- IGF-1 overexpression prevented age-related denervation and external Ca2+-dependent contraction.
- Targeting IGF-1 to motor neurons via TTC fusion protein also prevented this calcium dependence.
- IGF-1 treatment preserved nerve terminals at neuromuscular junctions.
Conclusions:
- Slow, age-related denervation of fast muscle fibers contributes to their reliance on external Ca2+ for force maintenance.
- IGF-1 plays a crucial role in preventing age-related denervation and preserving neuromuscular junction integrity, thereby mitigating contractile deficits in aging muscle.
