Identification of muscular senescence-related genes

• Project/Area Number: 22659066
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: TAKESHIMA Hiroshi 京都大学, 大学院・薬学研究科, 教授 (70212024)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,090,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: 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

Research Abstract

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.

Research Products

• [Journal Article] Endogenously determined restriction of food intake overcomes excitation-contraction uncoupling in JP45KO mice with aging (2012)
  • Author(s): Delbono, O., Messi M. L., Wang, Z., Treves, S., Mosca, B., Bergamelli, L., Nishi, M., Takeshima, H., Shi H., Xue B. & Zorzato, F
  • Journal Title: Exp. Gerontol Volume: 4 Issue: 4 Pages: 304-316
  • DOI: 10.1016/j.exger.2012.01.004
  • Peer Reviewed
• [Journal Article] Sarcalumenin plays a critical role in age-related cardiac dysfunction due to decreases in SERCA2a expression and activity. (2012)
  • Author(s): Jiao Q, et al.
  • Journal Title: Cell Calcium. Volume: 51 Issue: 1 Pages: 31-39
  • DOI: 10.1016/j.ceca.2011.10.003
  • Peer Reviewed
• [Journal Article] Imparied Orai1-mediateded resting Ca2+ entry reduces the cytosolic[Ca2+] and SR Ca2+ loading in quitescent junctophilin1 knockout myotubes (2010)
  • Author(s): Li, H., Ding, X., Lopez, J. R., Takeshima, H., Ma, J., Allen, P. D. & Eltit, J. M.
  • Journal Title: J. Biol. Chem Volume: 285 Issue: 50 Pages: 39171-39179
  • DOI: 10.1074/jbc.m110.149690
  • Peer Reviewed
• [Journal Article] Impaired Orail-mediated resting Ca^<2+> entry reduces the cytosolic [Ca^<2+>] and SR Ca^<2+> loading in quitescent junctophilin1 knockout myotubes. (2010)
  • Author(s): Li H, Ding X, Lopez JR, Takeshima H, Ma J, Allen PD, Eltit JM.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 39171-39179
  • Peer Reviewed
• [Remarks] 研究室ホームページ
  • URL: http://www.pharm.kyoto-u.ac.jp/biochem/
• [Remarks]
  • URL: http://www.pharm.kyoto-u.ac.jp/biochem/