Muscle aging is associated with compromised Ca2+ spark signaling and segregated intracellular Ca2+ release
Muscle aging is associated with compromised Ca2+ spark signaling and segregated intracellular Ca2+ release
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DOI：
10.1083/jcb.200604166
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发表时间：
2006-08-28
影响因子：
7.8
通讯作者：
Ma, Jianjie
中科院分区：
文献类型：
--
作者：
Weisleder, Noah;Brotto, Marco;Ma, Jianjie
细胞内Ca 2+（[Ca 2 +]（i））运动的稳态能力降低可能是肌肉老化过程中肌肉减少症和收缩功能障碍进展的基础。我们报告了与衰老相关的骨骼肌Ca 2+稳态的两种变化。Ca 2+火花，这是从肌浆网释放Ca 2+的基本单位，在年轻肌肉的静息条件下是沉默的，但在膜结构变形时以动态方式激活。在老年骨骼肌中，Ca 2+火花的动态性质似乎丢失。使用重复的电压刺激分离的肌肉制备，我们确定了一个隔离的[Ca 2 +] i储备，从正常的兴奋-收缩过程中，在老年骨骼肌解耦。在青少年肌肉中观察到类似的表型，其中一种名为mitsugumin-29（MG 29）的突触素家族蛋白质缺失，该蛋白质参与维持肌肉膜超微结构和Ca 2+信号传导。这一发现，加上MG 29在老年骨骼肌中的表达减少，表明MG 29的表达在维持骨骼肌Ca 2+稳态老化过程中是重要的。
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.