Identification of muscular senescence-related genes

骨质疏松症是指肌肉质量和力量随着年龄的增长而丧失。尽管几位研究人员已经报道了老化肌肉制剂中肌浆网(SR)的钙质处理受损，但石棺减少的直接原因仍有待彻底调查。我们设计通过比较年轻和老年小鼠肌肉标本的基因表达来寻找与肌质疏松症相关的SR蛋白。我们的基因芯片和生化分析发现，衰老小鼠的肌钙蛋白(Sarcalumenin，SAR)和肌浆/内质网钙(SERCA)含量均显著降低。SAR是一种主要的SR钙结合蛋白，SERCA负责SR钙摄取。根据以往的研究结果，SAR和SERCA在心肌和骨骼肌细胞中均定位于SR的纵向区域，我们合理地推测SAR可能与SERCA有功能关系。虽然我们之前已经建立了sar基因敲除小鼠品系，但突变小鼠没有表现出严重的心脏和肌肉缺陷。在Sar基因敲除的心脏中，SERCA含量减少，并在小鼠衰老过程中进一步下降。我们的观察表明，老化过程中SAR含量的减少可能会使SERCA不稳定，从而损害SR中的钙处理性能。另外，还检测了老年小鼠SR膜蛋白JP45和JP45的表达。不幸的是，在我们的分析中，没有发现SR蛋白与石棺减少之间的关系。

Sarcopenia is the loss of muscle mass and strength with age. The direct cause of sarcopenia remains to be exhaustively investigated, although several researchers have reported impaired Ca^<2+> handling of the sarcoplasmic reticulum(SR) in aged muscle preparations. We designed to search sarcopenia-related SR proteins by comparing gene expression between young-adult and aged mouse muscle preparations. Our gene chip and biochemical analyses found that both sarcalumenin(Sar) and sarco/endoplasmic reticulum Ca^<2+>-ATPase(SERCA) contents are significantly reduced in aged mice. Sar is a major SR Ca^<2+>-binding protein and SERCA is responsible for SR Ca^<2+> uptake. Based on the previous observations that Sar and SERCA are localized at the longitudinal region of the SR in both cardiac and skeletal muscle cells, we reasonably predicted that Sar may have functional relation with SERCA. Although we have previously established Sar-knockout mouse lines, the mutant mice exhibit no severe cardiac and muscular defects. In the Sar-knockout heart, SERCA content is reduced, and further decreased during mouse aging. Our observations suggest the possibility that reduced Sar content during aging may unstabilize SERCA to impair Ca^<2+>-handing performance in the SR. On the other hand, the SR membrane proteins junctophilin and JP45 were also examined in aged mice. Unfortunately, no relation between the SR proteins and sarcopenia was detected in our analysis.