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Elucidation of the mechanism by which myokines regulate aging progress

Research Project

Project/Area Number 21H03360
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionKyushu University

Principal Investigator

Kinugawa Shintaro  九州大学, 医学研究院, 准教授 (60399871)

Co-Investigator(Kenkyū-buntansha) 佐邊 壽孝  北海道大学, 遺伝子病制御研究所, 客員教授 (40187282)
高田 真吾  北翔大学, 生涯スポーツ学部, 准教授 (60722329)
松島 将士  九州大学, 医学研究院, 助教 (80552869)
横田 卓  北海道大学, 大学病院, 特任講師 (90374321)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2023: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2022: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2021: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywordsマイオカイン / 骨格筋 / 老化 / サルコペニア / プロテオーム解析
Outline of Research at the Start

健康長寿達成のためには、老化に伴うサルコペニア・フレイルを含む種々の臓器障害の分子基盤の解明および予防法の確立が必要である。近年、骨格筋から分泌されるマイオカインが注目されているが、老化進展におけるマイオカインの産生・分泌の全体像は明らかにされていない。本研究では、加齢性のマイオカイン異常が老化進展の要因であるという仮説を検証する。網羅的に経時的な加齢マイオカインプロファイリングを行い、動的バイオマーカー理論に基づく解析により、不可逆的老化への臨界特異点を明らかにする。個々のマイオカイン機能解析を行い、マイオカインをターゲットとしたこれまでに新たなパラダイムに基づく老化遅延策の構築を目指す。

Outline of Final Research Achievements

A myokine library was created by analyzing proteins secreted from skeletal muscle using mass spectrometry. In addition, by comparing the results of mass spectrometry analysis of blood from aging mice, we identified myokines that change with age (aging myokine profiling). We revealed that the secretion of brain-derived neurotrophic factor, a myokine, was decreased with age and was closely related to mitochondrial function and exercise capacity. We succeeded in observing the secretion dynamics of brain-derived neurotrophic factor in real time using a confocal microscope. As a result of comprehensive analysis of Rab proteins, it became clear that two types of Rab proteins may be involved in the secretion of myokines from C2C12 cells.

Academic Significance and Societal Importance of the Research Achievements

加齢によるマイオカイン分泌の全体像を捉えることはこれまでになかった独自の研究であり、本研究の学術的意義は極めて高い。加齢によって特異的に変化するマイオカインおよびそれらの分泌機構を明らかにすることによって、マイオカインによる新規薬物治療法の開発研究へ発展する。このことは、老化の共通基盤である骨格筋の量的・質的変化を予防・治療することにつながり、今後の健康長寿社会の実現に大きく寄与すると考えられ、社会的意義は高い。

Report

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

    (24 results)

All 2024 2023 2022 2021

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 13 results) Presentation (10 results) (of which Invited: 10 results)

  • [Journal Article] Association of baseline electrocardiographic left ventricular hypertrophy with future renal function decline in the general population2024

    • Author(s)
      Ikeda Shota、Shinohara Keisuke、Tagawa Koshiro、Tohyama Takeshi、Kishimoto Junji、Kazurayama Masaya、Tanaka Shinji、Yamaizumi Masamitsu、Nagayoshi Hirokazu、Toyama Kensuke、Matsushima Shouji、Tsutsui Hiroyuki、Kinugawa Shintaro
    • Journal Title

      Scientific Reports

      Volume: 14 Issue: 1

    • DOI

      10.1038/s41598-023-51085-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ZBP1 Protects Against mtDNA-Induced Myocardial Inflammation in Failing Hearts2023

    • Author(s)
      Enzan Nobuyuki、Matsushima Shouji、Ikeda Soichiro、Okabe Kosuke、Ishikita Akihito、Yamamoto Taishi、Sada Masashi、...Tsutsui Hiroyuki
    • Journal Title

      Circulation Research

      Volume: - Issue: 9 Pages: 1110-1126

    • DOI

      10.1161/circresaha.122.322227

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced mitochondrial oxidative metabolism in peripheral blood mononuclear cells is associated with fatty liver in obese young adults2023

    • Author(s)
      Shirakawa Ryosuke、Nakajima Takayuki、Yoshimura Aya、Kawahara Yukako、Orito Chieko、Yamane Miwako、Handa Haruka、Takada Shingo、Furihata Takaaki、Fukushima Arata、Ishimori Naoki、Nakagawa Masao、Yokota Isao、Sabe Hisataka、Hashino Satoshi、Kinugawa Shintaro、Yokota Takashi
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 5203-5203

    • DOI

      10.1038/s41598-023-32549-w

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of deep-learning models for real-time anaerobic threshold and peak VO2 prediction during cardiopulmonary exercise testing2023

    • Author(s)
      Watanabe Tatsuya、Tohyama Takeshi、Ikeda Masataka、Fujino Takeo、Hashimoto Toru、Matsushima Shouji、Kishimoto Junji、Todaka Koji、Kinugawa Shintaro、Tsutsui Hiroyuki、Ide Tomomi
    • Journal Title

      European Journal of Preventive Cardiology

      Volume: 31 Issue: 4 Pages: 448-457

    • DOI

      10.1093/eurjpc/zwad375

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cross-disease communication between cancer and heart failure provides a rational approach to prevention and treatment of both diseases2022

    • Author(s)
      Takada Shingo、Kinugawa Shintaro、Handa Haruka、Yokota Takashi、Sabe Hisataka
    • Journal Title

      Frontiers in Oncology

      Volume: 12 Pages: 1-5

    • DOI

      10.3389/fonc.2022.1006322

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ergogenic effects of caffeine are mediated by myokines2022

    • Author(s)
      Takada Shingo、Fumoto Yoshizuki、Kinugawa Shintaro
    • Journal Title

      Frontiers in Sports and Active Living

      Volume: 4 Pages: 1-8

    • DOI

      10.3389/fspor.2022.969623

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective roles of MITOL against myocardial senescence and ischemic injury partly via Drp1 regulation2022

    • Author(s)
      Tokuyama T、Uosaki H、Sugiura A、Nishitai G、Takeda K、Nagashima S、Shiiba I、Ito N、Amo T、Mohri S、Nishimura A、Nishida M、Konno A、Hirai H、Ishido S、Yoshizawa T、Shindo T、Takada S、Kinugawa S、Inatome R、Yanagi S
    • Journal Title

      iScience

      Volume: 25 Issue: 7 Pages: 104582-104582

    • DOI

      10.1016/j.isci.2022.104582

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Succinyl-CoA-based energy metabolism dysfunction in chronic heart failure2022

    • Author(s)
      Takada Shingo、Maekawa Satoshi、Furihata Takaaki、Kakutani Naoya、Setoyama Daiki、Ueda Koji、Nambu Hideo、Hagiwara Hikaru、Handa Haruka、Fumoto Yoshizuki、Hata Soichiro、Masunaga Tomoka、Fukushima Arata、Yokota Takashi、Kang Dongchon、Kinugawa Shintaro、Sabe Hisataka
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 41 Pages: 1-9

    • DOI

      10.1073/pnas.2203628119

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of xanthine oxidase in the acute phase of myocardial infarction prevents skeletal muscle abnormalities and exercise intolerance2021

    • Author(s)
      Nambu H, Takada S, Maekawa S, Matsumoto J, Kakutani N, Furihata T, Shirakawa R, Katayama T, Nakajima T, Yamanashi K, Obata Y, Nakano I, Tsuda M, Saito A, Fukushima A, Yokota T, Nio-Kobayashi J, Yasui H, Higashikawa K, Kuge Y, Anzai T, Sabe H, Kinugawa S
    • Journal Title

      Cardiovasc Res

      Volume: 117 Pages: 805-819

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Brain-derived neurotrophic factor improves impaired fatty acid oxidation via the activation of AMPKα-PGC1α signaling in skeletal muscle of mice with heart failure2021

    • Author(s)
      Matsumoto J, Takada S, Furihata T, Nambu H, Kakutani N, Maekawa S, Mizushima W, Nakano I, Fukushima A, Yokota T, Tanaka S, Handa H, Sabe H, Kinugawa S
    • Journal Title

      Circ Heart Fail

      Volume: 14

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cardiac-specific loss of mitoNEET expression is linked with age-related heart failure2021

    • Author(s)
      Furihata T, Takada S, Kakutani N, Maekawa S, Tsuda M, Matsumoto J, Mizushima W, Fukushima A, Yokota T, Enzan N, Matsushima S, Handa H, Fumoto Y, Nio-Kobayashi J, Iwanaga T, Tanaka S, Tsutsui H, Sabe H, Kinugawa S
    • Journal Title

      Commun Biol

      Volume: 4 Pages: 138-138

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Systemic oxidative stress is associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in heart failure patients2021

    • Author(s)
      Yokota T, Kinugawa S, Hirabayashi K, Yamato M, Takada S, Suga T, Nakano I, Fukushima A, Matsushima S, Okita K, Tsutsui H
    • Journal Title

      Sci Rep

      Volume: 11 Pages: 2272-2272

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Premedication with pioglitazone is preventable from doxorubicin-induced left ventricular dysfunction in mice2021

    • Author(s)
      Furihata T, Maekawa S, Takada S, Kakutani N, Nambu H, Shirakawa R, Yokota T, Kinugawa S
    • Journal Title

      BMC Pharmacol Toxicol

      Volume: 22 Pages: 874-874

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Angiotensin-converting enzyme inhibitor prevents skeletal muscle fibrosis in diabetic mice2021

    • Author(s)
      Kakutani N, Takada S, Nambu H, Maekawa S, Hagiwara H, Yamanashi K, Obata Y, Nakano I, Fumoto Y, Hata S, Furihata T, Yokota T, Fukushima A, Kinugawa S
    • Journal Title

      Exp Physiol

      Volume: 106 Pages: 1785-1793

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 心不全の骨格筋異常-マイオカインの役割2023

    • Author(s)
      絹川真太郎、髙田真吾、麓佳月
    • Organizer
      第29回日本心臓リハビリテーション学会学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 心不全における栄養療法2023

    • Author(s)
      髙田真吾、絹川真太郎
    • Organizer
      第29回日本心臓リハビリテーション学会学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 心不全における交感神経活性と運動療法2023

    • Author(s)
      絹川真太郎、松島将士、篠原啓介、池田翔大
    • Organizer
      第27回日本心不全学会学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Skeletal muscle abnormalities and myokines in heart failure2022

    • Author(s)
      絹川真太郎
    • Organizer
      日本循環器学会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 心不全における骨格筋エネルギー代謝異常2022

    • Author(s)
      絹川真太郎
    • Organizer
      日本心不全学会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] サルコペニア予防を目指した心不全治療2022

    • Author(s)
      絹川真太郎
    • Organizer
      日本心臓リハビリテーション学会北陸地方会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 心不全と骨格筋の基礎2021

    • Author(s)
      絹川真太郎
    • Organizer
      日本心臓リハビリテーション学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 心疾患の超急性期における骨格筋異常発症機序2021

    • Author(s)
      髙田真吾、絹川真太郎
    • Organizer
      日本心臓リハビリテーション学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] マイオカインとミトコンドリア:加齢や疾患における摂道2021

    • Author(s)
      絹川真太郎、髙田真吾、佐邊壽孝
    • Organizer
      日本生化学学会大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 不全心筋におけるミトコンドリア代謝リプログラミング2021

    • Author(s)
      髙田真吾、絹川真太郎、佐邊壽孝
    • Organizer
      日本生化学学会大会
    • Related Report
      2021 Annual Research Report
    • Invited

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

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