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Elucidation of the mechanism of age-related decline in muscle regenerative capacity and development of suppression methods

Research Project

Project/Area Number 19K09614
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionThe University of Tokushima (2021-2022)
Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology (2019-2020)

Principal Investigator

UEZUMI Madoka  徳島大学, 大学院医歯薬学研究部(医学域), 特任講師 (70435866)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords骨格筋 / 老化 / 再生
Outline of Research at the Start

高齢者において転倒や骨折に伴う筋損傷からの回復の遅れは、要介護状態への進行の主要原因であり、健康寿命延長のために解決すべき重要課題である。我々は加齢に伴う筋再生能力の低下が骨格筋内環境の悪化に起因することを明らかにしており、老化及び若齢マウスの再生筋組織を用いた網羅的タンパク発現解析から、老化再生筋で発現が顕著に低下し、環境悪化に寄与し得る因子を同定した。本研究では、この因子の筋再生における機能を明らかにし、老化マウスへの補充により筋再生能力を改善できるか否か検証する。

Outline of Final Research Achievements

Delayed recovery from muscle injury caused by falls and fractures in the elderly is an important problem to be solved because it causes the transition to nursing care or bedridden status. To elucidate the cause of age-related decline in muscle regenerative capacity, we performed a comprehensive protein expression analysis using regenerating muscle of aged and young mice and identified a factor that is down-regulated in aged mice. Mice deficient in this factor showed delayed muscle regeneration. The factor was suggested to function in the removal of necrotic fibers, and the deficient mice showed decreased proliferation of skeletal muscle stem cells and decreased number of regenerating myofibers, suggesting that prolonged inflammation and residual necrotic fibers cause the delayed regeneration. This study elucidated one of the mechanisms of age-related decline in muscle regenerative capacity, and the results are expected to lead to the development of preventive and therapeutic methods.

Academic Significance and Societal Importance of the Research Achievements

現在、我が国では平均寿命と健康寿命の間に約10年の乖離があり、健康寿命を延伸させることが喫緊の課題となっている。高齢者において転倒や骨折に伴う筋損傷からの回復の遅れは、要介護や寝たきりへの移行原因となり、健康寿命延伸のために解決すべき重要課題である。しかしながら、筋再生能力低下の原因は未だ不明な点が多く、改善方法も確立されていない。本研究は、老齢及び若齢再生筋組織を用いた網羅的タンパク発現比較解析から、これまで筋再生への関与が知られていなかった分子を同定し、老化による筋再生能力低下機序の一端を解明するものであり、この成果は予防・治療法の開発へと発展が期待できる。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (16 results)

All 2023 2022 2021 2020 2019

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 10 results) Presentation (5 results) (of which Invited: 1 results)

  • [Journal Article] Analyses of Mesenchymal Progenitors in Skeletal Muscle by Fluorescence-Activated Cell Sorting and Tissue Clearing2023

    • Author(s)
      Ikemoto-Uezumi M, Kurosawa T, Minato K, Uezumi A
    • Journal Title

      Methods Mol Biol

      Volume: 2640 Pages: 117-127

    • DOI

      10.1007/978-1-0716-3036-5_9

    • ISBN
      9781071630358, 9781071630365
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Whole-mount immunofluorescence staining of mesenchymal progenitors in murine plantaris muscle.2022

    • Author(s)
      Kurosawa T, Ikemoto-Uezumi M, Kaneshige A, Fukada S, Uezumi A
    • Journal Title

      STAR Protocols

      Volume: 3(3) Issue: 3 Pages: 101593-101593

    • DOI

      10.1016/j.xpro.2022.101593

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of muscle stem cell-derived myonuclei in murine overloaded muscles2022

    • Author(s)
      Kaneshige A, Kaji T, Saito H, Higashimoto T, Nakamura A, Kurosawa T, Ikemoto-Uezumi M, Uezumi A, Fukada S
    • Journal Title

      STAR Protocols

      Volume: -

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tenogenic Induction From Induced Pluripotent Stem Cells Unveils the Trajectory Towards Tenocyte Differentiation2022

    • Author(s)
      Yoshimoto Yuki、Uezumi Akiyoshi、Ikemoto-Uezumi Madoka、Tanaka Kaori、Yu Xinyi、Kurosawa Tamaki、Yambe Shinsei、Maehara Kazumitsu、Ohkawa Yasuyuki、Sotomaru Yusuke、Shukunami Chisa
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 10 Pages: 780038-780038

    • DOI

      10.3389/fcell.2022.780038

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased MFG‐E8 at neuromuscular junctions is an exacerbating factor for sarcopenia‐associated denervation2021

    • Author(s)
      Ikemoto‐Uezumi Madoka、Zhou Heying、Kurosawa Tamaki、Yoshimoto Yuki、Toyoda Masashi、Kanazawa Nobuo、Nakazawa Tatsu、Morita Mitsuhiro、Tsuchida Kunihiro、Uezumi Akiyoshi
    • Journal Title

      Aging Cell

      Volume: 21 Issue: 1 Pages: 1-15

    • DOI

      10.1111/acel.13536

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relayed signaling between mesenchymal progenitors and muscle stem cells ensures adaptive stem cell response to increased mechanical load.2021

    • Author(s)
      Kaneshige A, Kaji T, Zhang L, Saito H, Nakamura A, Kurosawa T, Ikemoto-Uezumi M, Tsujikawa K, Seno S, Hori M, Saito Y, Matozaki T, Maehara K, Ohkawa Y, Potente M, Watanabe S, Braun T, Uezumi A, Fukada SI.
    • Journal Title

      Cell Stem Cell.

      Volume: 29 Issue: 2 Pages: 265-280

    • DOI

      10.1016/j.stem.2021.11.003

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Measurement of Lateral Transmission of Force in the Extensor Digitorum Longus Muscle of Young and Old Mice2021

    • Author(s)
      Minato K, Yoshimoto Y, Kurosawa T, Watanabe K, Kawashima H, Ikemoto-Uezumi M, Uezumi A
    • Journal Title

      Int J Mol Sci

      Volume: 22 Issue: 22 Pages: 12356-12356

    • DOI

      10.3390/ijms222212356

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transgenic Expression of Bmp3b in Mesenchymal Progenitors Mitigates Age-Related Muscle Mass Loss and Neuromuscular Junction Degeneration2021

    • Author(s)
      Kurosawa Tamaki、Minato Keitaro、Ikemoto-Uezumi Madoka、Hino Jun、Tsuchida Kunihiro、Uezumi Akiyoshi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 19 Pages: 10246-10246

    • DOI

      10.3390/ijms221910246

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Liver fibrosis-induced muscle atrophy is mediated by elevated levels of circulating TNFα2021

    • Author(s)
      Kurosawa Tamaki、Goto Momo、Kaji Noriyuki、Aikiyo Satoshi、Mihara Taiki、Ikemoto-Uezumi Madoka、Toyoda Masashi、Kanazawa Nobuo、Nakazawa Tatsu、Hori Masatoshi、Uezumi Akiyoshi
    • Journal Title

      Cell Death & Disease

      Volume: 12 Issue: 1 Pages: 11-11

    • DOI

      10.1038/s41419-020-03353-5

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mesenchymal Bmp3b expression maintains skeletal muscle integrity and decreases in age-related sarcopenia2021

    • Author(s)
      Uezumi Akiyoshi、Ikemoto-Uezumi Madoka、Zhou Heying、Kurosawa Tamaki、Yoshimoto Yuki、Nakatani Masashi、Hitachi Keisuke、Yamaguchi Hisateru、Wakatsuki Shuji、Araki Toshiyuki、Morita Mitsuhiro、Yamada Harumoto、Toyoda Masashi、Kanazawa Nobuo、Nakazawa Tatsu、Hino Jun、Fukada So-ichiro、Tsuchida Kunihiro
    • Journal Title

      Journal of Clinical Investigation

      Volume: 131 Issue: 1

    • DOI

      10.1172/jci139617

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Methods for Accurate Assessment of Myofiber Maturity During Skeletal Muscle Regeneration2020

    • Author(s)
      Yoshimoto Yuki、Ikemoto-Uezumi Madoka、Hitachi Keisuke、Fukada So-ichiro、Uezumi Akiyoshi
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 8 Pages: 267-267

    • DOI

      10.3389/fcell.2020.00267

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 神経筋接合部におけるMFG-E8の蓄積は加齢性脱神経の増悪因子である2023

    • Author(s)
      上住 円
    • Organizer
      第8回日本筋学会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 神経筋接合部から見る骨格筋老化のメカニズム2021

    • Author(s)
      上住円
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 神経筋接合部におけるMFG-E8の蓄積は加齢性脱神経の一因となる2020

    • Author(s)
      上住円、周赫英、吉本由紀、黒澤珠希、湊圭太郎、上住聡芳
    • Organizer
      第6回日本筋学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 神経筋接合部におけるMFG-E8の異常蓄積が骨格筋老化に及ぼす影響2019

    • Author(s)
      上住円、周赫英、黒澤珠希、吉本由紀、上住聡芳
    • Organizer
      第7回若手による骨格筋細胞研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] カルシトニン受容体の発現低下は加齢性の骨格筋幹細胞減少に寄与する2019

    • Author(s)
      上住円、上住聡芳、張礫丹、周赫英、橋下有弘、岡村菊夫、松井康素、塚崎晃士、細山徹、中谷直史、森田充浩、山田治基、土田邦博、深田宗一朗
    • Organizer
      第5回日本筋学会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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