Muscle aging is associated with compromised Ca2+ spark signaling and segregated intracellular Ca2+ release.
Reduced homeostatic capacity for intracellular Ca2+ ([Ca2+]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.
Weisleder
Noah
N
Department of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Brotto
Marco
M
Komazaki
Shinji
S
Pan
Zui
Z
Zhao
Xiaoli
X
Nosek
Thomas
T
Parness
Jerome
J
Takeshima
Hiroshi
H
Ma
Jianjie
J
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002413:Cations, Divalent; D004558:Electric Stimulation; D006706:Homeostasis; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D009997:Osmotic Pressure; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism
D002413:Cations, Divalent; C111842:Mg29 protein, mouse; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D016708:Synaptophysin; D002118:Calcium