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Elucidation of pathogenesis of sarcopenia based on the mechanism of metabolic changes of skeletal muscle

Research Project

Project/Area Number 16H03266
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied health science
Research InstitutionTokyo Metropolitan Geriatric Hospital and Institute of Gerontology

Principal Investigator

Shigemoto Kazuhiro  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 副所長 (40284400)

Co-Investigator(Kenkyū-buntansha) 森 秀一  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (30508677)
本橋 紀夫  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (50532727)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywordsサルコペニア / フレイル / 代謝変換 / 筋線維タイプ変化 / バイオマーカー / 早期診断 / 予防 / 筋萎縮 / 筋線維タイプ / 生体内因子 / 動物モデル / 骨格筋 / モデル動物
Outline of Final Research Achievements

In the process leading to sarcopenia and muscle atrophy, unidirectional skeletal muscle fiber type change (sarcopenia: fast muscle → slow muscle) occurs. We are conducting research with the aim of clarifying the causal relationship between muscle fiber type changes (metabolic changes) and the mechanism of sarcopenia and muscle atrophy, and linking it to the development of methods for preventing and treating sarcopenia and muscle atrophy. Each muscle fiber type has its own energy metabolic properties, and in this study different metabolic properties of mice. We have developed MusColor mice that allow all four types of muscle fiber types that have alive to be distinguished alive with different fluorescent proteins. Using this MusColor technology, we have found in vivo factors that induce muscle fiber type changes (metabolism conversion) and studied the mechanism.

Academic Significance and Societal Importance of the Research Achievements

MusColorマウス由来の筋幹細胞を用いて骨格筋線維の代謝変換を誘導する物質(生体内因子や薬物など)の同定に関する新技術(MusColor技術)の特許出願を果たし、日米の特許に加えて欧州特許が2018年5月に成立させた. このMusColor技術を使い、これまで、100 種類以上の市販の生体内因子・マイオカイン・薬物などを用いてMyHC-I,IIa, IIx或はIIbを発現する筋線維を顕著に誘導あるいは抑制する物質のスクリーニングを実行して候補分子を複数同定している. この新技術はサルコペニア・フレイルのメカニズム解明、早期診断法および有効な介入法の開発に有用であると期待される.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (44 results)

All 2018 2017 2016 Other

All Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (29 results) (of which Int'l Joint Research: 9 results,  Invited: 10 results) Remarks (2 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 2 results)

  • [Journal Article] Tbx1 regulates inherited metabolic and myogenic abilities of progenitor cells derived from slow- and fast-type muscle2018

    • Author(s)
      Motohashi Norio、Uezumi Akiyoshi、Asakura Atsushi、Ikemoto-Uezumi Madoka、Mori Shuuichi、Mizunoe Yuhei、Takashima Rumi、Miyagoe-Suzuki Yuko、Takeda Shin’ichi、Shigemoto Kazuhiro
    • Journal Title

      Cell Death & Differentiation

      Volume: 印刷中 Issue: 6 Pages: 1024-1036

    • DOI

      10.1038/s41418-018-0186-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Practical Anatomy of the Neuromuscular Junction in Health and Disease.2018

    • Author(s)
      Nishimune H and Shigemoto K.
    • Journal Title

      Neurologic Clinics.

      Volume: 36 Issue: 2 Pages: 231-240

    • DOI

      10.1016/j.ncl.2018.01.009

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] サルコペニア・フレイルのメカニズムと脳卒中.2018

    • Author(s)
      重本 和宏, 森 秀一, 本橋 紀夫, 高嶋 留美
    • Journal Title

      分子脳血管病

      Volume: 17 Pages: 119-122

    • Related Report
      2018 Annual Research Report
  • [Journal Article] サルコペニアの概念とその診断方法.2018

    • Author(s)
      重本 和宏, 森 秀一, 本橋 紀夫, 高嶋 留美
    • Journal Title

      臨床と病理

      Volume: 136 Pages: 128-134

    • Related Report
      2018 Annual Research Report
  • [Journal Article] サルコペニ・アフレイルの基礎研究の現状.2018

    • Author(s)
      重本 和宏, 森 秀一, 本橋 紀夫, 高嶋 留美
    • Journal Title

      日本臨床増刊号

      Volume: 上 Pages: 189-193

    • Related Report
      2018 Annual Research Report
  • [Journal Article] フレイルのバイオマーカー探索.2018

    • Author(s)
      重本 和宏, 森 秀一, 本橋 紀夫, 高嶋 留美
    • Journal Title

      最新医学別冊

      Volume: 別冊 Pages: 67-73

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Immunization of mice with LRP4 induces myasthenia similar to MuSK-associated myasthenia gravis.2017

    • Author(s)
      Mori S, Motohashi N, Takashima R, Kishi M, Nishimune H, Shigemoto K.
    • Journal Title

      Experimental Neurology

      Volume: 297 Pages: 158-167

    • DOI

      10.1016/j.expneurol.2017.08.006

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dual-color STED microscopy reveals a sandwitch structure of Bassoon and Piccolo in active zones of adult and aged mice.2016

    • Author(s)
      Nishimune H, Badwi Y, Mori S, Shigemoto K
    • Journal Title

      Scientific Report

      Volume: 6,27935 Issue: 1

    • DOI

      10.1038/srep27935

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] サルコペニア発症における神経経の関与2016

    • Author(s)
      重本 和宏、森 秀一, 本橋 紀夫
    • Journal Title

      最新醫學別冊 診断と治療のABC112

      Volume: 診断と治療のABC112 Pages: 40-46

    • Related Report
      2016 Annual Research Report
  • [Presentation] Identification of novel molecular mediators of muscle fiber-type switch2018

    • Author(s)
      Norio Motohashi, Shuuichi Mori, Rumi Takashima and Kazuhiro Shigemoto
    • Organizer
      Cell Symposia:Multifaceted Mitochondria
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A new ex vivo electrophysiological neuro-muscular evaluation of mouse; In case of Guillain-Barre syndrome.2018

    • Author(s)
      Kishi M, Mori S, Koga M, Shigemoto K, Konishi T, Sakakibara R, Tateno F, Aiba Y
    • Organizer
      14th International Congress of Neuroimmunology, Brisbane (Australia)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of screening system for identification of novel factors influencing muscle fiber types2018

    • Author(s)
      Norio Motohashi, Shuuichi Mori, Rumi Takashima and Kazuhiro Shigemoto
    • Organizer
      Molecular mechanisms of muscle wasting during aging and disease, Ascona, Switzerland
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Declining muscle plasticity in sarcopenia and frailty.2018

    • Author(s)
      Kazuhiro Shigemoto
    • Organizer
      4th Asian Conference For Frailty and Sarcopenia, Daling, China
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inter-muscular injection of m. triangularis sterni: A new ex vivo evaluation of mouse NMJ.2018

    • Author(s)
      Kishi M, Mori S, Shigemoto K, Sakakibara R, Tateno F, Aiba Y, Konishi T.
    • Organizer
      第59回日本神経学会学術大会, 札幌
    • Related Report
      2018 Annual Research Report
  • [Presentation] サルコペニア・フレイルを予防するためになぜ運動や栄養が大切か?2018

    • Author(s)
      重本 和宏
    • Organizer
      第87回愛宕臨床栄養研究会, 東京慈恵医科大学
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 筋線維タイプを識別できるMusColorマウスの開発2018

    • Author(s)
      本橋 紀夫, 森 秀一, 高嶋 留美, 重本 和宏
    • Organizer
      第4回日本筋学会, 岡山(倉敷)
    • Related Report
      2018 Annual Research Report
  • [Presentation] サルコペニア・フレイルのメカニズムの解明に向けて,2018

    • Author(s)
      重本 和宏
    • Organizer
      第40回臨床栄養学会総会、第39回臨床栄養協会総会、東京
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] NMJ由来タンパク質の血中バイオマーカーとしての有用性検討,2018

    • Author(s)
      森 秀一, 本橋 紀夫, 高嶋 留美, 重本 和宏
    • Organizer
      第73回日本体力医学会, 福井
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mouse Model of LRP4-MG.2017

    • Author(s)
      Mori S, Motohashi N, Takashima R, Kishi M and Nishimune H and Shigemoto K
    • Organizer
      13th International Conference on Myasthenia Gravis and Related Disorders conference.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impairment of presynaptic functions and structures of NMJ in mice with Lrp4 induced myasthenia.2017

    • Author(s)
      Shigemoto K, Mori S, Motohashi N, Takashima R, Kishi M and Nishimune H
    • Organizer
      XXII World Congress of Neurology.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of novel factors influencing muscle fiber type transition2017

    • Author(s)
      Motohashi N, Mori S, Takashima R and Shigemoto K.
    • Organizer
      2017 Keystone Symposia Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経筋接合部からみたサルコペニアのメカニズム研究について.2017

    • Author(s)
      重本 和宏
    • Organizer
      第3回日本筋学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] サルコペニア発症のメカニズム2017

    • Author(s)
      重本 和宏
    • Organizer
      第17回日本抗加齢医学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] フレイルのメカニズム研究の現状について2017

    • Author(s)
      重本 和宏
    • Organizer
      第30回日本老年学会/第40回日本基礎老化学会大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 抗Lrp4抗体陽性重症筋無力症の自己免疫動物モデルの作成2017

    • Author(s)
      森秀一, 本橋紀夫, 高嶋留美, 岸雅彦, 西宗裕史, 重本和宏
    • Organizer
      日本神経学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Lrp4の機能抑制による神経筋刺激伝達の変化2017

    • Author(s)
      森秀一, 本橋紀夫, 高嶋留美, 岸雅彦, 重本和宏
    • Organizer
      第72回日本体力医学会大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 骨格筋代謝制御因子の同定2017

    • Author(s)
      本橋 紀夫, 朝倉 淳, 森 秀一, 高嶋 留美, 上住円, 上住聡芳, 重本 和宏
    • Organizer
      第3回日本筋学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Super Resolution Microscopy Analysis of NMJ Active Zones in Adult and Aged Mice2016

    • Author(s)
      Badawi Y, Mori S, Shigemoto K, Nishimune H
    • Organizer
      Neuroscience 2016
    • Place of Presentation
      San Diego(USA)
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dying-back neuropathy as a cause and predictor of sarcopenia.2016

    • Author(s)
      Shigemoto K
    • Organizer
      2nd Asian Conference for Frailty and Sarcopenia
    • Place of Presentation
      Nagoya(Japan)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] サルコペニアの病態と薬物治療の可能性2016

    • Author(s)
      重本 和宏
    • Organizer
      第16回日本抗加齢医学会総会
    • Place of Presentation
      パシフィコ横浜会議センター(神奈川県・横浜)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 老化マウス神経筋シナプスのプレシナプス蛋白の構造解析2016

    • Author(s)
      重本 和宏
    • Organizer
      第39回日本基礎老化学会
    • Place of Presentation
      伊勢原市民文化会館(伊勢原市・神奈川県)
    • Related Report
      2016 Annual Research Report
  • [Presentation] STED顕微鏡によるマウス神経筋シナプスのプレシナプス蛋白の構造解析2016

    • Author(s)
      重本和宏, Yomma Badawi, 森秀一、Hiroshi Nishimune
    • Organizer
      第39回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜会議センター(神奈川県・横浜)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Structural analysis of active zone proteins in mouse NMJ using STED microscopy2016

    • Author(s)
      重本和宏, Yomma Badawi, 森秀一、Hiroshi Nishimune
    • Organizer
      第2回日本筋学会
    • Place of Presentation
      国立精神神経センター(東京都・小平市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] microRNAによる骨格筋幹細胞の維持機構2016

    • Author(s)
      本橋 紀夫, 森 秀一, 高嶋 留美, 重本 和宏
    • Organizer
      第71回日本体力医学会大会
    • Place of Presentation
      盛岡市民文化ホール(岩手県・盛岡市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 新規筋線維タイプ変換誘導因子の探索2016

    • Author(s)
      本橋 紀夫, 森 秀一, 山崎 綾乃, 高嶋 留美, 重本 和宏
    • Organizer
      第4回若手による骨格筋細胞研究会
    • Place of Presentation
      ウインクあいち(愛知県・名古屋市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 老化マウスの神経筋シナプスのプレシナプス蛋白の構造変化2016

    • Author(s)
      重本和宏、Yomma Badawi, 森秀一、Hiroshi Nishimune
    • Organizer
      第3回サルコペニアフレイル研究会
    • Place of Presentation
      今池ガスビルホール(愛知県・名古屋)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Structural analysis of active zones in NMJ of aged-mouse using STED microscopy2016

    • Author(s)
      Shigemoto K, Badawi Y, Mori S, and Nisnimune H
    • Organizer
      Frontiers in aging research toward healthy longevity
    • Place of Presentation
      丸の内MY PLAZAホール(東京都・千代田区)
    • Related Report
      2016 Annual Research Report
  • [Presentation] STED顕微鏡によるマウス神経筋シナプスのプレシナプス蛋白の構造解析2016

    • Author(s)
      重本和宏、Yomma Badawi, 森秀一、Hiroshi Nishimune
    • Organizer
      第39回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜会議センター(神奈川県・横浜市)
    • Related Report
      2016 Annual Research Report
  • [Remarks] 東京都健康長寿医療センター研究所 老年病態研究チーム運動器医学研究

    • URL

      https://www.tmghig.jp/research/team/rounenbyotai/undokiigaku/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 東京都健康長寿医療センター研究所老年病態研究チーム運動器医学

    • URL

      http://www.tmghig.jp/J_TMIG/kenkyu/team/undokiigaku.html

    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] Muscle Stem Cell Or Myoblast, Method For Screening Substances That Participate In Metabolic2018

    • Inventor(s)
      Kazuhiro Shigemoto
    • Industrial Property Rights Holder
      Tokyo Metro Inst of Gerontology
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Acquisition Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 筋幹細胞又は筋芽細胞、及びそれを用いた代謝変換に関与する物質のスクリーニング方法、並びにスクリーニング方法によって得られた物質を含む医薬組成物2016

    • Inventor(s)
      重本 和宏
    • Industrial Property Rights Holder
      地方独立行政法人東京都健康長寿医療センター
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016
    • Acquisition Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] MUSCLE STEM CELL OR MYOBLAST, METHOD FOR SCREENING SUBSTANCES THAT PARTICIPATE IN METABOLIC CONVERSION USING SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING SUBSTANCE OBTAINED FROM SAID2016

    • Inventor(s)
      重本 和宏
    • Industrial Property Rights Holder
      地方独立行政法人東京都健康長寿医療センター
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016
    • Acquisition Date
      2017
    • Related Report
      2017 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 加齢または筋萎縮の診断用バイオマーカー2016

    • Inventor(s)
      重本 和宏
    • Industrial Property Rights Holder
      地方独立行政法人東京都健康長寿医療センター
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016
    • Acquisition Date
      2017
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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