Excitation-Contraction Coupling Regulation in Aging Skeletal Muscle

Osvaldo Delbono

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Abstract
Aging is associated with decreasing strength that can lead to impaired performance of daily living activities in the elderly. Functional and structural decline in the neuromuscular system has been recognized as a cause of this impairment and loss of independence, but the age-related loss of strength is greater than the loss of muscle mass in mammals, including humans, and the underlying mechanisms remain only partially understood. This chapter focuses on skeletal muscle excitation-contraction uncoupling (ECU), external calcium-dependent skeletal muscle contraction, the role of JP-45 and other recently discovered molecules of the muscle T-tubule-sarcoplasmic reticulum junction (triad) in excitation-contraction coupling (ECC), the neural influence of skeletal muscle, and the role of trophic factorsparticularly insulin-like growth factor-I (IGF-1)in structural and functional modifications of the motor unit and the neuromuscular junction with aging. A better understanding of the triad proteins involved in muscle ECC and nerve/muscle interactions and their regulation will lead to more rational interventions to delay or prevent muscle weakness with aging.