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Molecular Mechanisms of Muscle Redox Signaling in Exercise and Injury

Research Project

Project/Area Number 19K11560
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59020:Sports sciences-related
Research InstitutionNippon Medical School

Principal Investigator

Wolf Alexander  日本医科大学, 医学部, 講師 (20434136)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Discontinued (Fiscal Year 2020)
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsレドックス / 酸化ストレス / 運動 / redox / exercise / injury / roGFP / imaging / in vivo imaging
Outline of Research at the Start

Exercise remains the most powerful intervention to increase health span in humans, slowing down or even preventing functional decline in old age.
The key scientific question here is to determine the molecular mechanism(s) of redox signalling during exercise, and if these can be manipulated beneficially in vivo. Redox signaling is reportedly defective in aging, blunting the benefits of exercise in the elderly. Restoring redox signaling might be a crucial factor in reaping the benefits of exercise in elderly individuals.

Outline of Annual Research Achievements

Exercise remains the most powerful intervention to increase health span in humans and is widely advocated to slow down or even prevent the functional decline occurring in old age. Exercise builds muscle mass, which prevents frailty, increases mobility, as a consequence, quality of life. Nevertheless, the molecular mechanisms by which exercise builds muscle mass are not well understood. Oxidative stress has long been seen as a negative consequence of exercise, but more recent results suggest that reducing oxidative stress can prevents the beneficial effects of exercise, underscoring its importance in signaling during training.
Using transgenic mice expressing a ratiometric redox-sensitive fluorescent protein (roGFP) in mitochondrial or cytosol, we will record the spatio-temporal dynamics of cellular redox state in skeletal muscle of live animals using in vivo imaging. We already found that muscle fiber injury plays an important role in redox signaling during exercise and accompanying muscle fiber injury, but did not yet identify the pathway(s) transmitting this signal. We will work towards identifying the danger associated molecular patterns (DAMPs) released by injured muscle fibers and the receptors causing the observed redox transients in adjacent tissue. Suitable in vitro models will also be employed, with the overall goal of gaining insights that might help design interventions that increase the positive effects of exercise.

One publication and one book chapter was published during parental leave.

Current Status of Research Progress
Current Status of Research Progress

4: Progress in research has been delayed.

Reason

The principal investigator was on parental leave until December 2020. The project was restarted in March 2021, when the principal investigator returned to work. No funds were used during the reporting period.

研究代表者が交付決定の時点で5人目の子供の誕生で育児休業を取得しその後育児休業を2020年12月まで延長したので当該年度に大半で研究が中断中でした。
育児休業の開始年月日及び終了年月日: 平成3 0 年1 2 月2 7 日 ~ 令和2 年12 月2 6 日
研究代表者が2021年3月1日から復職し、主に論文作成に当たりました。

Strategy for Future Research Activity

これから論文作成を続けます。

Report

(2 results)
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (2 results)

All 2021 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Book (1 results)

  • [Journal Article] MtDNA mutations and aging - not a closed case after all?2021

    • Author(s)
      Wolf Alexander M.
    • Journal Title

      Signal Transduction and Targeted Therapy

      Volume: 6 Issue: 1 Pages: 56-56

    • DOI

      10.1038/s41392-021-00479-6

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Book] 最新皮膚エイジングメカニズムと高機能性シワ改善化粧品の開発 - ブルーライトによる光老化のメカニズムと予防2020

    • Author(s)
      ウォルフ アレクサンダー M.
    • Total Pages
      310
    • Publisher
      シーエムシー出版
    • ISBN
      4781315127
    • Related Report
      2020 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2021-12-27  

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