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A novel treatment for sarcopenia targeting mitochondrial dynamics and autophagy

Research Project

Project/Area Number 17K09309
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General internal medicine(including psychosomatic medicine)
Research InstitutionKagoshima University

Principal Investigator

Akasaki Yuichi  鹿児島大学, 医歯学域鹿児島大学病院, 助教 (00631920)

Co-Investigator(Kenkyū-buntansha) 池田 義之  鹿児島大学, 医歯学域医学系, 講師 (00573023)
大石 充  鹿児島大学, 医歯学域医学系, 教授 (50335345)
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsミトコンドリア / ミトコンドリア機能 / サルコペニア / 老化 / 酸化ストレス / アンジオテンシン / 骨格筋減少 / オートファジー / 内科 / 生理学 / シグナル伝達 / 発現制御
Outline of Final Research Achievements

Aging-related sarcopenia is regarded as a cause of deterioration of activity and metabolic capacity of the elderly. Since it is important to prevent this age-related muscle loss, we examined to clarify the cause and the therapeutic target of sarcopenia. Aging and oxidative stress caused mitochondrial dysfunction and suppressed skeletal muscle repair. These were improved by inhibiting angiotensin receptor, which suggested that this mechanism would be a therapeutic target for aging-related skeletal muscle loss.

Academic Significance and Societal Importance of the Research Achievements

加齢に伴う骨格筋減少は、高齢者の総死亡率についての予測因子になりうる。ミトコンドリアは、ミトコンドリアダイナミクスという、細胞環境に応じて別のミトコンドリアと融合すること(Fusion)や分離すること(Fission)で、バランスをとっている。老化に伴う骨格筋のミトコンドリア形態変化については、このバランス不均衡が骨格筋の加齢性機能低下に関与することが疑われている。本研究において、老化や酸化ストレスは、ミトコンドリアの機能異常を引き起こし、骨格筋修復を抑制していた。これらは、アンジオテンシン受容体への作用を阻害することで改善したため、この機序が骨格筋減少の治療標的になることが示唆された。

Report

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

    (38 results)

All 2020 2019 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (23 results) (of which Int'l Joint Research: 8 results) Book (10 results)

  • [Journal Article] Estrogen-SIRT1 Axis Plays a Pivotal Role in Protecting Arteries Against Menopause-Induced Senescence and Atherosclerosis2020

    • Author(s)
      Sasaki Y, Ikeda Y, Miyauchi T, Uchikado Y, Akasaki Y, Ohishi M.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 27 Issue: 1 Pages: 47-59

    • DOI

      10.5551/jat.47993

    • NAID

      130007779023

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2020-01-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Use of proton pump inhibitors is associated with an increase in adverse cardiovascular events in patients with hemodialysis: Insight from the kids registry2020

    • Author(s)
      Kosedo I, Tokushige A, Takumi T, Yoshikawa A, Teraguchi K, Takenouchi K, Shiraishi K, Ikeda D, Imamura M, Sonoda T, Kanda D, Ikeda Y, Ido A, Ohishi M.
    • Journal Title

      Eur J Intern Med

      Volume: 72 Issue: 4 Pages: 79-87

    • DOI

      10.1080/10641963.2019.1649685

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cerebrovascular and cardiovascular diseases caused by drugs of abuse.2020

    • Author(s)
      Akasaki Y, Ohishi M.
    • Journal Title

      Hypertens Res.

      Volume: - Issue: 5 Pages: 363-371

    • DOI

      10.1038/s41440-019-0367-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Questionnaire survey from the viewpoint of concordance in patient and physician satisfaction concerning hypertensive treatment in elderly patients-patients voice study.2018

    • Author(s)
      Ikeda Y, Sasaki T, Kuwahata S, Imamura M, Tanoue K, Komaki S, Hashiguchi M, Kuroda A, Akasaki Y, Hamada C, Ohishi M
    • Journal Title

      Circ J

      Volume: 82 Pages: 1051-1061

    • NAID

      130006528641

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Impact of Autophagy on Cardiovascular Senescence and Diseases2017

    • Author(s)
      Sasaki Y, Ikeda Y, Iwabayashi M, Akasaki Y, Ohishi M.
    • Journal Title

      International Heart Journal

      Volume: 58 Issue: 5 Pages: 666-673

    • DOI

      10.1536/ihj.17-246

    • NAID

      130006179212

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Metabolic stress causes sarcopenia via angiotensin II type I receptor signal-induced mitochondrial fission.2019

    • Author(s)
      Akasaki Y, Ikeda Y, Uchikado Y, Sasaki Y, Higuchi K, Ohishi M.
    • Organizer
      第83回 日本循環器学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Estrogen/Sirt1/LKB1/AMPK axis plays a crucial role in mediating Rab9-dependent mitophagy and retarding arterial senescence.2019

    • Author(s)
      Sasaki Y, Ikeda Y, Akasaki Y, Uchikado Y, Higuchi K, Ohishi M.
    • Organizer
      第83回 日本循環器学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Metabolic stress and angiotensin II causes vascular senescence via AT1R signal-mediate mitochondrial fission.2019

    • Author(s)
      Uchikado Y, Ikeda Y, Sasaki Y, Akasaki Y, Higuchi K, Ohishi M.
    • Organizer
      第83回 日本循環器学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] コントロール不良高血圧の要因分析 -垂水研究からの考察-2019

    • Author(s)
      赤﨑雄一、窪薗琢郎、杉浦剛、牧迫飛雄馬、田平隆行、桑波田聡、竹中俊宏、大石充
    • Organizer
      第8回臨床高血圧フォーラム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 未治療高血圧の要因分析 -垂水研究からの考察-2019

    • Author(s)
      赤﨑雄一、窪薗琢郎、杉浦剛、牧迫飛雄馬、田平隆行、桑波田聡、竹中俊宏、大石充
    • Organizer
      第8回臨床高血圧フォーラム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 高血圧治療における患者の理解や患者―医師間の満足度は前期高齢者と後期高齢者で異なる特徴をもつ.2019

    • Author(s)
      池田義之, 佐々木 健, 桑波田 聡, 今村正和, 赤﨑雄一, 大石 充.
    • Organizer
      第61回 日本老年医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 血圧・血圧変動とサルコペニア・軽度認知機能障害の関係:垂水研究.2019

    • Author(s)
      赤﨑雄一, 窪薗琢郎, 池田義之, 富岡一俊, 桑波田 聡, 竹中俊宏, 牧迫飛雄馬, 大石 充.
    • Organizer
      第61回 日本老年医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 生活習慣病による血管老化にAngiotensin2 Type1受容体を介したmitochondrial fissionは重要な役割を果たす.2019

    • Author(s)
      内門義博, 池田義之, 佐々木雄一, 赤﨑雄一, 大石 充.
    • Organizer
      第61回 日本老年医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] CAVI上昇は, 血圧変動の独立した危険因子である:超高齢者社会を迎えた鹿児島県垂水市における健康調査の結果から.2019

    • Author(s)
      赤﨑雄一, 窪薗琢郎, 池田義之, 大石 充.
    • Organizer
      第51回 日本動脈硬化学会総会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ox-LDLやAGEによる血管老化にAngiotensinII type1受容体を介したmitochondrial fissionは重要な役割を果たす.2019

    • Author(s)
      内門義博, 池田義之, 佐々木雄一, 赤﨑雄一, 大石 充.
    • Organizer
      第51回 日本動脈硬化学会総会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ox-LDLによる血管老化にAngiotensinⅡTypeⅠ受容体を介したmitochondrial fissionは重要な役割を果たす.2019

    • Author(s)
      内門義博, 池田義之, 佐々木雄一, 赤﨑雄一, 大石 充.
    • Organizer
      第67回 日本心臓病学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Oxidized Low Density Lipoprotein and Angiotensin II Causes Vascular Senescence Via AT1R Signal-mediate Mitochondrial Fission.2019

    • Author(s)
      Uchikado Y, Ikeda Y, Sasaki Y, Akasaki Y, Ohishi M.
    • Organizer
      AHA Basic Cardiovascular Science 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Estrogen Protects Artery from Senescence via Sirt1/AMPK/Rab9-mediated Mitophagy.2018

    • Author(s)
      Sasaki Y, Ikeda Y, Akasaki Y, Uchikado Y, Ohishi M
    • Organizer
      AHA Basic Cardiovascular Science 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Questionnaire survey from the viewpoint of concordance in patient and physician satisfaction concerning hypertensive treatment in elderly patients(patients voice study).2018

    • Author(s)
      Akasaki Y, Ikeda Y, Sasaki Y, Kuwahata S, Sasaki Y, Ohishi M
    • Organizer
      ISH 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Metabolic stress evokes mitochondrial dysfunction and vascular senescence via mitochondrial fission.2018

    • Author(s)
      Uchikado Y, Ikeda Y, Sasaki Y, Akasaki Y, Ohishi M
    • Organizer
      The 2nd JCS Council Forum on Basic Cardiovascular Research
    • Related Report
      2018 Research-status Report
  • [Presentation] Metabolic stress evokes muscular mitochondrial dysfunction and sarcopenia via angiotensin II type I receptor signal induced mitochondrial fission.2018

    • Author(s)
      Akasaki Y, Ikeda Y, Uchikado Y, Sasaki Y, Higuchi K, Ohishi M
    • Organizer
      American Heart Association Scientific Sessions 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Inhibition of angiotensin II type I receptor retards development of cellular senescence and atherosclerosis via augmentation of Rab9-dependent mitophagy.2018

    • Author(s)
      Sasaki Y, Ikeda Y, Iwabayashi M, Akasaki Y, Higuchi K, Miyata M, Ohishi M
    • Organizer
      第82回日本循環器学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Estrogen maintains mitochondrial function and retards vascular senescence via Rab9-dependent mitohpagy.2018

    • Author(s)
      Sasaki Y, Ikeda Y, Iwabayashi M, Akasaki Y, Higuchi K, Miyata M, Ohishi M
    • Organizer
      第82回日本循環器学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 高齢者における血圧変動と心血管疾患および身体機能の関係2018

    • Author(s)
      赤﨑雄一、大石 充
    • Organizer
      第41回日本高血圧学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Renin-angiotensin signal develops arterial senescence and atherosclerosis via modulation of mitochondrial dynamics.2017

    • Author(s)
      Ikeda Y, Iwabayashi M, Sasaki Y, Akasaki Y, Higuchi K, Miyata M, Ohishi M.
    • Organizer
      AHA Council on Hypertension 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Switching insufficient hypotensive monotherapy to ARB/CCB combination tablet in elderly patients increases both patient and physician satisfaction rates and contributes better patient-physician concordance (Patients Voice study).2017

    • Author(s)
      Ikeda Y, Sasaki T, Kuwahata S, Akasaki Y, Hamada C, Ohishi M.
    • Organizer
      AHA Council on Hypertension 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Selective estrogen receptor modulator retards arterial senescence and atherosclerosis via upregulation of eNOS/Sirt-1 pathway in post^menopause model mouse.2017

    • Author(s)
      Sasaki Y, Ikeda Y, Iwabayashi M, Miyauchi T, Akasaki Y, Higuchi K, Miyata M, Ohishi M.
    • Organizer
      The 8th Congress of the International Society for Gender Medicine
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Estrogen-induced alternative autophagy plays a crucial role in protecting artery from senescence and atherosclerosis.2017

    • Author(s)
      Sasaki Y, Ikeda Y, Iwabayashi M, Akasaki Y, Higuchi K, Miyata M, Ohishi M.
    • Organizer
      American Heart Association 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Book] 血圧2019

    • Author(s)
      赤﨑雄一、大石 充
    • Total Pages
      6
    • Publisher
      先端医学社
    • Related Report
      2019 Annual Research Report
  • [Book] 循環器内科2019

    • Author(s)
      赤﨑雄一、大石 充
    • Total Pages
      6
    • Publisher
      科学評論社
    • Related Report
      2019 Annual Research Report
  • [Book] Geriatric Medicine2019

    • Author(s)
      赤﨑雄一、大石 充
    • Total Pages
      4
    • Publisher
      ライフ・サイエンス
    • Related Report
      2019 Annual Research Report
  • [Book] 心臓2018

    • Author(s)
      赤﨑雄一、大石 充
    • Publisher
      日本医学出版
    • Related Report
      2018 Research-status Report
  • [Book] カレントテラピー2018

    • Author(s)
      赤﨑雄一、大石 充
    • Publisher
      ライフメディコム
    • Related Report
      2018 Research-status Report
  • [Book] 血圧2018

    • Author(s)
      赤﨑雄一、大石 充
    • Publisher
      先端医学社
    • Related Report
      2018 Research-status Report
  • [Book] 血圧2017

    • Author(s)
      赤﨑雄一、大石充
    • Publisher
      先端医学社
    • Related Report
      2017 Research-status Report
  • [Book] 1336専門家による私の治療2017

    • Author(s)
      赤﨑雄一、大石充
    • Publisher
      日本医事新報社
    • Related Report
      2017 Research-status Report
  • [Book] 診療ガイドラインUP-TO-DATE 2018-20192017

    • Author(s)
      赤﨑雄一、大石充
    • Publisher
      メディカルレビュー社
    • Related Report
      2017 Research-status Report
  • [Book] カレントテラピー2017

    • Author(s)
      赤﨑雄一、大石充
    • Publisher
      ライフメディコム
    • Related Report
      2017 Research-status Report

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

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