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Development of therapies for sarcopenia focusing on novel cell death mechanisms

Research Project

Project/Area Number 21K21271
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0909:Sports sciences, physical education, health sciences, and related fields
Research InstitutionNagasaki International University

Principal Investigator

Eshima Hiroaki  長崎国際大学, 人間社会学部, 講師 (80759259)

Project Period (FY) 2021-08-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords骨格筋 / 活性酸素 / サルコペニア / 筋力 / 過酸化脂質 / 細胞死 / 治療法
Outline of Research at the Start

超高齢化社会をむかえたわが国では、加齢による筋量・筋力の減少(サルコペニア)を予
防することが健康寿命に直結する。本研究は、サルコペニア発症時における新規細胞死機構の関連性を明らかにすることを目的とし、骨格筋における新規細胞死機構の予防がサルコペニア発症の防止に繋がるか否か検証する。本研究の成果は、新規細胞死機構を評価指標としたサルコペニアに対する予防法・治療法の新展開に繋がることが期待できる。

Outline of Final Research Achievements

This study investigated whether ferroptosis, a novel cell death mechanism, is associated with sarcopenia. We firts found that glutathione reductase 4 (Gpx4), a ferroptosis-related molecule, was significantly decreased at the protein level in skeletal muscle of aged mice compared to young mice. We also found Gpx4 overexpressed muscle significantly higher muscle mass and muscle strength during aging. Therefore, we clarified that ferroptosis is a novel mechanism for sarcopenia.

Academic Significance and Societal Importance of the Research Achievements

超高齢化社会をむかえたわが国では、加齢による筋量・筋力の減少(サルコペニア)を予防することが健康寿命に直結する。本研究はサルコペニアの原因となる活性酸素の新たな中枢機構を見出し、サルコペニアの新規治療法となる機構を発見した。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (6 results)

All 2023 2022 2021 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Remarks (1 results)

  • [Journal Article] Lipid hydroperoxides promote sarcopenia through carbonyl stress2023

    • Author(s)
      Eshima Hiroaki、Shahtout Justin L、Siripoksup Piyarat、Funai Katsuhiko et al.
    • Journal Title

      eLife

      Volume: 12

    • DOI

      10.7554/elife.85289

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impaired fatigue resistance, sarcoplasmic reticulum function, and mitochondrial activity in soleus muscle of db/db mice2022

    • Author(s)
      Yamamoto H, Eshima H, Kakehi S, Kawamori R, Watada H, Tamura Y.
    • Journal Title

      Physiol Rep.

      Volume: 10 Issue: 18

    • DOI

      10.14814/phy2.15478

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metformin and leucine increase satellite cells and collagen remodeling during disuse and recovery in aged muscle2021

    • Author(s)
      Petrocelli Jonathan J.、Mahmassani Ziad S.、Fix Dennis K.、Montgomery Jessie A.、Reidy Paul T.、McKenzie Alec I.、Hart Naomi M.、Ferrara Patrick J.、Kelley Joshua J.、Eshima Hiroaki、Funai Katsuhiko、Drummond Micah J.
    • Journal Title

      The FASEB Journal

      Volume: 35 Issue: 9

    • DOI

      10.1096/fj.202100883r

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Low lysophosphatidylcholine induces skeletal muscle myopathy that is aggravated by high‐fat diet feeding2021

    • Author(s)
      Ferrara Patrick J.、Verkerke Anthony R. P.、Maschek J. Alan、Shahtout Justin L.、Siripoksup Piyarat、Eshima Hiroaki、Johnson Jordan M.、Petrocelli Jonathan J.、Mahmassani Ziad S.、Green Thomas D.、McClung Joseph M.、Cox James E.、Drummond Micah J.、Funai Katsuhiko
    • Journal Title

      The FASEB Journal

      Volume: 35 Issue: 10

    • DOI

      10.1096/fj.202101104r

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Influence of Obesity and Type 2 Diabetes on Calcium Handling by Skeletal Muscle: Spotlight on the Sarcoplasmic Reticulum and Mitochondria2021

    • Author(s)
      Eshima Hiroaki
    • Journal Title

      Frontiers in Physiology

      Volume: 12 Pages: 758316-758316

    • DOI

      10.3389/fphys.2021.758316

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Remarks] 江島研究室

    • URL

      http://eshimahiroaki.com/

    • Related Report
      2021 Research-status Report

URL: 

Published: 2021-10-22   Modified: 2024-01-30  

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