Muscle aging is associated with compromised Ca(2+) spark signaling and segregated intracellular Ca(2+) release

Reduced homeostatic capacity for intracellular Ca(2+) ([Ca(2+)](i)) movement may underlie the progression of sarcopenia and contractile dysfunction during muscle aging. We report two alterations to Ca(2+) homeostasis in skeletal muscle that are associated with aging. Ca(2+) sparks, which are the elemental units of Ca(2+) 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 Ca(2+) sparks appears to be lost in aged skeletal muscle. Using repetitive voltage stimulation on isolated muscle preparations, we identify a segregated [Ca(2+)](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 Ca(2+) signaling. This finding, coupled with decreased expression of MG29 in aged skeletal muscle, suggests that MG29 expression is important in maintaining skeletal muscle Ca(2+) homeostasis during aging.