Muscle aging is associated with compromised Ca²⁺ spark signaling and segregated intracellular Ca²⁺ release

Reduced homeostatic capacity for intracellular Ca²⁺ ([Ca ²⁺]_i) movement may underlie the progression of sarcopenia and contractile dysfunction during muscle aging. We report two alterations to Ca²⁺ homeostasis in skeletal muscle that are associated with aging. Ca²⁺ sparks, which are the elemental units of Ca²⁺ release from sarcoplasmic reticulum, are silent under resting conditions in young muscle, yet activate in a dynamic manner upon deformation of membrane structures. The dynamic nature of Ca²⁺ sparks appears to be lost in aged skeletal muscle. Using repetitive voltage stimulation on isolated muscle preparations, we identify a segregated [Ca²⁺]_i reserve that uncouples from the normal excitation-contraction process in aged skeletal muscle. Similar phenotypes are observed in adolescent muscle null for a synaptophysin-family protein named mitsugumin-29 (MG29) that is involved in maintenance of muscle membrane ultrastructure and Ca²⁺ signaling. This finding, coupled with decreased expression of MG29 in aged skeletal muscle, suggests that MG29 expression is important in maintaining skeletal muscle Ca²⁺ homeostasis during aging.