Functional and structural decline of the neuromuscular system is a recognized cause of decreased strength, impaired performance of daily living activities, and loss of independence in the elderly. However, in mammals, including humans, age-related loss of strength is greater than loss of muscle mass, so the underlying mechanisms remain only partially understood. This review focuses on the mechanisms underlying impaired skeletal muscle function with aging, including external calcium-dependent skeletal muscle contraction; increased voltage-sensitive calcium channel Cav1.1 β1asubunit and junctional face protein JP-45 and decreased Cav1.1 (α1) expression, and the potential role of these and other recently discovered molecules of the muscle T-tubule/sarcoplasmic reticulum junction in excitation-contraction uncoupling. We also examined neural influences and trophic factors, particularly insulin-like growth factor-I (IGF-1). Better insight into the triad proteins involvement in muscle ECC and nerve/muscle interactions and regulation will lead to more rational interventions to delay or prevent muscle weakness with aging. The focus of this review is on the proteins mediating excitation-contraction coupling (ECC) and their expression and regulation in humans and rodent models of skeletal muscle functional decline with aging. Age-dependent changes in proteins other than those related to ECC, muscle composition, clinical assessment and interventions, have been extensively reviewed recently [1-3].
Keywords: skeletal muscle, aging, sarcopentia, insulin-like growth factor 1, excitation-contraction coupling, denervation, fatigue, protein kinases, motor neuron, spinal cord
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