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Molecular mechanism of autophagy-dependent functional defect in sarcopenia

Research Project

Project/Area Number 17K01755
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Sports science
Research InstitutionTokyo Institute of Technology

Principal Investigator

Sakuma Kunihiro  東京工業大学, リベラルアーツ研究教育院, 教授 (60291176)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsオートファジー / サルコペニア / 骨格筋 / マイトファジー / 筋線維 / 加齢 / 除神経 / 筋萎縮 / 萎縮
Outline of Final Research Achievements

Autophagy dysfunction occurs in sarcopenia (age-related myopathy). Using age-related and denervated muscles, we compared the manner of adaptive changes of mitophagy (mitochondrial autophagy: Parkin) and chaperone-mediated autophagy (Bag3) and aimed to develop a shorter, more convenient model of autophagy dysfunction in sarcopenia. Our result shows that the changes in autophagy-related modulation of ageing muscles occurs in the denervated muscles. It was found to be partially reproducible.

Academic Significance and Societal Importance of the Research Achievements

最近筋萎縮の分野で注目を浴びているのは、ノーベル医学生理学賞を受賞したオートファジー(自食)という機構である。高齢マウスの大腿四頭筋の筋線維において、オートファジー関連物質 (p62)の免疫活性が異常に亢進していることを以前我々は証明した (Sakuam K et al., JCSM, 2016)。すなわちサルコペニア(加齢性筋減弱症)おいてオートファジーの機能不全が認められるが、この現象の短期間モデルがこれまで開発できていなかった。本研究の結果から、加齢筋で特徴的なオートファジー機能不全は、除神経筋において部分的に再現できることが明らかになった。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (21 results)

All 2019 2018 2017

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 7 results) Book (7 results)

  • [Journal Article] Secreted Protein Acidic and Rich in Cysteine (SPARC) improves glucose tolerance via AMP-activated protein kinase activation2019

    • Author(s)
      Aoi, W., Hirano, N., Lassiter, D.G., Björnholm, M., Chibalin, A.V., Sakuma, K., Tanimura, Y., Mizushima, K., Takagi, T., Naito, Y., Zierath, J.R., Krook, A.
    • Journal Title

      FASEB J.

      Volume: 33 Issue: 9 Pages: 10551-10652

    • DOI

      10.1096/fj.201900453r

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] タンパク分解とサルコペニアの機構2019

    • Author(s)
      佐久間邦弘
    • Journal Title

      Geriatric Medicine

      Volume: 57 Pages: 775-779

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 高齢者にアミノ酸の摂取は有効か2019

    • Author(s)
      佐久間邦弘
    • Journal Title

      介護予防・健康づくり

      Volume: 6 Pages: 47-48

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Recent advances in pharmacological, hormonal, nutritional intervention for sarcopenia2018

    • Author(s)
      Sakuma K, Yamaguchi A
    • Journal Title

      Pflugers Archiv

      Volume: 470 Issue: 3 Pages: 449-460

    • DOI

      10.1007/s00424-017-2077-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Resveratrol attenuates denervation-induced muscle atrophy due to the blockade of atrogin-1 and p62 accumulation2018

    • Author(s)
      Asami Y, Aizawa M, Kinoshita M, Ishikawa J, Sakuma K
    • Journal Title

      International Journal of Medical Sciences

      Volume: 15 Issue: 6 Pages: 628-637

    • DOI

      10.7150/ijms.22723

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] サルコペニア発症の分子機構2017

    • Author(s)
      佐久間邦弘
    • Journal Title

      日本サルコペニア・フレイル学会雑誌

      Volume: 1 Pages: 19-22

    • Related Report
      2017 Research-status Report
  • [Journal Article] Molecular mechanism of sarcopenia and cachexia: recent research advances.2017

    • Author(s)
      Sakuma K, Aoi W, Yamaguchi A
    • Journal Title

      Pflugers Archiv

      Volume: 印刷中 Issue: 5-6 Pages: 573-591

    • DOI

      10.1007/s00424-016-1933-3

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 加齢筋におけるオートファジー機能不全と肥満による影響2019

    • Author(s)
      佐久間邦弘
    • Organizer
      第6回日本サルコペニア・フレイル学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] サルコペニアの分子メカニズムとその軽減方法2019

    • Author(s)
      佐久間邦弘
    • Organizer
      第74回日本体力医学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] オートファジー機能不全によるサルコペニア2018

    • Author(s)
      佐久間邦弘.
    • Organizer
      第5回日本サルコペニアフレイル学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] サルコペニアのメカニズムとリハ栄養の可能性2018

    • Author(s)
      佐久間邦弘
    • Organizer
      第8回日本リハビリテーション栄養学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] シンポジウム3 専門外でもよくわかるサルコペニアの分子生物学・細胞生物学 "オートファジー機能不全によるサルコペニア"2017

    • Author(s)
      佐久間邦弘
    • Organizer
      第4回日本サルコペニア・フレイル学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] シンポジウム1 サルコペニア研究の基礎科学と臨床の間にあるもの. サルコペニアの発症メカニズム:オートファジー機能不全に着目して2017

    • Author(s)
      佐久間邦弘
    • Organizer
      第72回日本体力医学会大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Autophagy-dependent Signaling in Sarcopenic Muscle2017

    • Author(s)
      Kunihiro Sakuma
    • Organizer
      3rd Asian Conference for Frailty and Sarcopenia
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] Sarcopenia: Molecular, Cellular, and Nutritional Aspects, 1st Edition2019

    • Author(s)
      Kunihiro Sakuma, Hidetaka Wakabayashi, Akihiko Yamaguchi
    • Total Pages
      432
    • Publisher
      CRC Press
    • ISBN
      9781498765138
    • Related Report
      2019 Annual Research Report
  • [Book] Muscular Dystrophies2019

    • Author(s)
      Kunihiro Sakuma
    • Total Pages
      117
    • Publisher
      InTech Open
    • ISBN
      9781789238464
    • Related Report
      2019 Annual Research Report
  • [Book] Muscle Atrophy2018

    • Author(s)
      Sakuma K, Yamaguchi A
    • Total Pages
      624
    • Publisher
      Springer Nature
    • ISBN
      9789811314346
    • Related Report
      2018 Research-status Report
  • [Book] Muscle Cell and Tissue: Current Status of Research Field2018

    • Author(s)
      Sakuma K
    • Total Pages
      358
    • Publisher
      InTech Open
    • ISBN
      9781789840063
    • Related Report
      2018 Research-status Report
  • [Book] Frailty and Sarcopenia - Onset, Development and Clinical Challenges2017

    • Author(s)
      Kotomi S, Sakuma K
    • Total Pages
      243
    • Publisher
      InTech
    • ISBN
      9789535134831
    • Related Report
      2017 Research-status Report
  • [Book] The Plasticity of Skeletal Muscle-from Molecular Mechanism to Clinical Applications-2017

    • Author(s)
      Sakuma K, Aizawa M, Wakabayashi H, Yamaguchi A
    • Total Pages
      292
    • Publisher
      Springer Nature
    • ISBN
      9789811032912
    • Related Report
      2017 Research-status Report
  • [Book] Physical Disabilities- Therapeutic Implications2017

    • Author(s)
      Iida Y, Sakuma K
    • Total Pages
      168
    • Publisher
      InTech
    • ISBN
      9789535132486
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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