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Mechanisms of skeletal muscle remodeling processes activated by exercise and attenuated by aging

Research Project

Project/Area Number 21K08530
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionThe University of Tokushima (2023)
Kobe University (2021-2022)

Principal Investigator

NOMURA Kazuhiro  徳島大学, 大学院医歯薬学研究部(医学域), 講師 (70450236)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords骨格筋 / 肥満 / エネルギー代謝 / アドレナリンシグナル / サルコペニア / 運動 / 加齢 / 骨格筋リモデリング
Outline of Research at the Start

骨格筋組織では収縮に伴い機械的損傷が生じ、回復再生を絶えず繰り返している。このような骨格筋のリモデリングプロセスには骨格筋細胞、筋衛星細胞、炎症細胞、さらにこれらの細胞から分泌される液性因子が筋損傷部位において統合的協調的に関与していると考えられている。これらのメカニズムは運動で活性化される一方、加齢とともに低下することが知られているが、運動時のいかなるシグナルが寄与しているのかその実体は明らかではない。本研究では、サルコペニアの新規治療法の開発を念頭に、運動によって活性化され、加齢とともに低下する骨格筋リモデリングプロセスの起点となるシグナルの実体を明らかにする。

Outline of Final Research Achievements

In skeletal muscle of aging mice, the accumulation of inflammatory cells is known to be delayed during the repair and remodeling process of damaged muscle, but this delayed accumulation of inflammatory cells is ameliorated in mice that that undergo training exercise. In "exercise-resistant" skeletal muscle-specific β2-adrenergic receptor-deficient mice, the accumulation of inflammatory cells during the repair and remodeling process of damaged muscle was delayed, and no improvement was observed with exercise. These results led to the identification of several candidate factors involved in signals that are attenuated by aging and activated by exercise.

Academic Significance and Societal Importance of the Research Achievements

本研究では運動によって活性化され、加齢によって減弱する骨格筋リモデリングプロセスの起点となるシグナルに関わる候補因子の同定に至った。このような因子の解析をさらにすすめることで、サルコペニアの新規な治療法・治療薬の開発に発展させることが期待できる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (24 results)

All 2023 2022 2021 Other

All Int'l Joint Research (6 results) Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (15 results) (of which Int'l Joint Research: 5 results,  Invited: 6 results) Remarks (2 results)

  • [Int'l Joint Research] Karolinska Institutet(スウェーデン)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Columbia University/New York University(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Karolinska Institutet(スウェーデン)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Columbia University/New York University(米国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Karolinska Institutet(スウェーデン)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Columbia University/New York University(米国)

    • Related Report
      2021 Research-status Report
  • [Journal Article] A Piezo1/KLF15/IL-6 axis mediates immobilization-induced muscle atrophy2022

    • Author(s)
      Yu Hirata, Kazuhiro Nomura, Daisuke Kato, Yoshihisa Tachibana, Takahiro Niikura, Kana Uchiyama, Tetsuya Hosooka, Tomoaki Fukui, Keisuke Oe, Ryosuke Kuroda, Yuji Hara, Takahiro Adachi, Koji Shibasaki, Hiroaki Wake, Wataru Ogawa
    • Journal Title

      Journal of Clinical Investigation

      Volume: - Issue: 10 Pages: 1-13

    • DOI

      10.1172/jci154611

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 脳内炎症は骨格筋のC/EBP経路を介してストレス性筋萎縮を促進する2023

    • Author(s)
      内山奏、平田悠、野村和弘、Hendy Wijaya、谷口将之、北岡志保、古屋敷智之、小川渉
    • Organizer
      第66回糖尿病学会年次学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 不動化における筋量制御のメカニズム2023

    • Author(s)
      平田悠、野村和弘、小川渉
    • Organizer
      第96回日本内分泌学会学術総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 骨格筋による新たな体温維持機構の発見とその制御分子の同定2023

    • Author(s)
      和泉優奈、藤本紗織、谷口萌々花、大村皐月、志内哲也、岡松優子、米代武司、黒田雅士、野村和弘、堤理恵、阪上浩
    • Organizer
      第9回日本筋学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 脳内炎症は骨格筋のC/EBP経路を介してストレス性筋萎縮を促進する2023

    • Author(s)
      内山 奏、平田悠、野村和弘、Hendy Wijaya、谷口 将之、北岡 志保、古屋敷 智之、小川渉
    • Organizer
      第58回日本臨床分子医学会学術総会
    • Related Report
      2023 Annual Research Report
  • [Presentation] A Piezo1/KLF15/IL-6 axis mediates immobilization-induced muscle atrophy2023

    • Author(s)
      Hirata Y, Nomura K, Ogawa W
    • Organizer
      The 50th European Muscle Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Role of myofiber Piezo1 in skeletal muscle hypertrophy induced by mechanical load2023

    • Author(s)
      Inoue T, Hirata Y, Nomura K, Ogawa W
    • Organizer
      The 50th European Muscle Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mental stress induces muscle atrophy through brain inflammation and the C/EBPβδ pathway in skeletal muscle2023

    • Author(s)
      Uchiyama K, Hirata Y, Nomura K, Wijaya H, Taniguchi M, Kitaoka S, Furuyashiki T, Ogawa W
    • Organizer
      The 50th European Muscle Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of Imeglimin on Mitochondrial Function, AMPK Activation, and Gene Expression in Hepatocytes and Myocytes2023

    • Author(s)
      Hozumi K, Sugawara K, Hirata Y, Nomura K, Ogawa W
    • Organizer
      The 50th European Muscle Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 糖尿病による筋量減少の分子機構2022

    • Author(s)
      小川 渉、平田 悠、野村 和弘
    • Organizer
      第95回日本内分泌学会学術総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 運動による骨格筋リモデリングの活性化と加齢による破綻メカニズム2022

    • Author(s)
      野村和弘、小川渉
    • Organizer
      第65回日本糖尿病学会年次学術集会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 高血糖および不動化における筋量制御のメカニズム2022

    • Author(s)
      平田悠、野村和弘、小川渉
    • Organizer
      第65回日本糖尿病学会年次学術集会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] ストレスはC/EBP-KLF15経路を介して筋萎縮を促進する2022

    • Author(s)
      内山奏、平田悠、野村和弘、Hendy Wijaya、谷口将之、北岡志保、古屋敷智之、小川渉
    • Organizer
      第65回日本糖尿病学会年次学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 運動による代謝改善とその破綻メカニズム -ヒト骨格筋のエピゲノム解析も踏まえて-2021

    • Author(s)
      野村和弘、小川渉
    • Organizer
      第64回日本糖尿病学会年次学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 高血糖および不動化における筋量制御のメカニズム2021

    • Author(s)
      平田悠、野村和弘、小川渉
    • Organizer
      第64回日本糖尿病学会年次学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Changes in Skeletal Muscle DNA Methylation in Rats Following Concurrent High-Fat Diet and Exercise Training2021

    • Author(s)
      Katayama M, Nomura K, Mudry J, Chibalin A, Krook A, Zierath J
    • Organizer
      Meeting of the Scandinavian Physiological Society 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Remarks] 神戸大学大学院医学研究科 糖尿病・内分泌内科学

    • URL

      http://www.med.kobe-u.ac.jp/im2/

    • Related Report
      2023 Annual Research Report 2022 Research-status Report 2021 Research-status Report
  • [Remarks] 徳島大学大学院医歯薬学研究部 代謝栄養学分野

    • URL

      https://taishaeiyo.jimdofree.com/

    • Related Report
      2023 Annual Research Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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