Identification of muscular senescence-related genes

肌肉减少症是肌肉质量和力量随着年龄的增长而减少。尽管一些研究者已经报道了衰老肌肉标本中肌浆网（SR）的Ca^2+处理受损，但肌肉减少症的直接原因仍有待彻底研究。本研究旨在通过比较成年小鼠和老年小鼠肌肉标本中基因表达的差异，寻找与肌肉减少症相关的SR蛋白。基因芯片和生化分析发现，老年小鼠肌钙素（sarcalumenin，Sar）和肌质/内质网Ca^<2+>-ATP酶（sarco/endoplasmic reticulum Ca^<2+>-ATPase，SERCA）含量均显著降低。Sar是主要的SR Ca^<2+>结合蛋白，而SERCA负责SR Ca^<2+>摄取。基于先前的观察，即Sar和SERCA定位于心肌和骨骼肌细胞SR的纵向区域，我们合理地预测Sar可能与SERCA有功能关系。虽然我们以前已经建立了SAR基因敲除小鼠品系，突变小鼠没有表现出严重的心脏和肌肉缺陷。在Sar敲除的心脏中，SERCA含量降低，并且在小鼠衰老期间进一步降低。我们的观察结果表明，衰老过程中Sar含量的减少可能会使SERCA不稳定，从而损害SR中的Ca^2+处理性能。另一方面，我们还在老年小鼠中检测了SR膜蛋白junctophilin和JP 45。不幸的是，在我们的分析中没有检测到SR蛋白和肌肉减少症之间的关系。

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.