Identification of muscular senescence-related genes

肌肉衰老相关基因的鉴定

• 批准号: 22659066
• 负责人: TAKESHIMA Hiroshi
• 金额: $ 1.98万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659066/
• 关键词: サルコペニア; 筋老化; 筋萎縮; 筋小胞体; Ca^<2+>ハンドリング; サルカルメニン; 小胞体Ca2+ポンプ; 加齢骨格筋; 心不全; Ca2+ハンドリング; 筋委縮; 遺伝子発現; 病態マーカー; microRNA

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.

肌肉减少症是指随着年龄的增长肌肉质量和力量的减少。肌少症的直接原因仍有待深入研究，尽管一些研究人员已经报道了衰老肌肉制剂中肌浆网（SR）的Ca^<2+>处理受损。我们设计通过比较青壮年和老年小鼠肌肉制剂的基因表达来寻找与肌肉减少症相关的SR蛋白。我们的基因芯片和生化分析发现，老年小鼠的sarcalumenin（Sar）和sarco/内质网Ca^<2+>- atp酶（SERCA）含量显著降低。Sar是主要的SR Ca^<2+>结合蛋白，SERCA负责SR Ca^<2+>摄取。根据之前的观察，Sar和SERCA都定位于心脏和骨骼肌细胞SR的纵向区域，我们合理地预测Sar可能与SERCA有功能关系。虽然我们之前已经建立了敲除sar的小鼠系，但突变小鼠没有表现出严重的心脏和肌肉缺陷。在敲除sar的心脏中，SERCA含量降低，并在小鼠衰老过程中进一步降低。我们的观察结果表明，衰老过程中Sar含量的降低可能会使SERCA不稳定，从而损害SR中Ca^<2+>的处理性能。另一方面，我们也在老年小鼠中检测了SR膜蛋白junctophilin和JP45。不幸的是，在我们的分析中没有发现SR蛋白与肌肉减少症之间的关系。

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Impaired Orail-mediated resting Ca^<2+> entry reduces the cytosolic [Ca^<2+>] and SR Ca^<2+> loading in quitescent junctophilin1 knockout myotubes.

受损的Orail介导的静息Ca^2进入减少了静止的junctophilin1敲除肌管中的胞质[Ca^2]和SR Ca^2负载。

• 发表时间: 2010
• 期刊: J.Biol.Chem.
• 作者: Li H;Ding X;Lopez JR;Takeshima H;Ma J;Allen PD;Eltit JM.
• 通讯作者: Eltit JM.

Endogenously determined restriction of food intake overcomes excitation-contraction uncoupling in JP45KO mice with aging.

• DOI: 10.1016/j.exger.2012.01.004
• 发表时间: 2012-04
• 期刊: EXPERIMENTAL GERONTOLOGY
• 影响因子: 3.9
• 作者: Delbono, Osvaldo;Messi, Maria Laura;Wang, Zhong-Min;Treves, Susan;Mosca, Barbara;Bergamelli, Leda;Nishi, Miyuki;Takeshima, Hiroshi;Shi, Hang;Xue, Bingzhong;Zorzato, Francesco
• 通讯作者: Zorzato, Francesco