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Epigenetic mechanism of aged muscle atrophy and decreased regeneration

Research Project

Project/Area Number 18K18461
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Studies on the Super-Aging Society
Research InstitutionKyoto Prefectural University

Principal Investigator

Kamei Yasutomi  京都府立大学, 生命環境科学研究科, 教授 (70300829)

Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords骨格筋 / 筋萎縮 / エピジェネティクス / サルコペニア / 加齢 / 筋再生 / 筋サテライト細胞 / DNAメチル化
Outline of Final Research Achievements

During atrophy such as aging (sarcopenia), the muscle regeneration capacity after injury is known to be decreased, which leads to impaired muscle function as well as more severe sarcopenia with lower quality of life. In this study, we observed that DNA methyltransferase 3a (Dnmt3a) expression is decreased after muscle atrophy. The regeneration capacity after muscle injury was markedly decreased in Dnmt3a-KO mice. Dnmt3a-KO satellite cell, important for muscle regeneration, showed suppressed myotube differentiation. Expression of Gdf5 was markedly increased in Dnmt3a-KO mice. The DNA methylation level of the Gdf5 promoter was markedly decreased in Dnmt3a-KO satellite cells, suggesting Gdf5 expression is regulated by DNA methylation. Thus, Dnmt3a appears to regulate satellite cell differentiation via DNA methylation. This mechanism may play a role in the decreased regeneration capacity during atrophy such as in aged sarcopenia.

Academic Significance and Societal Importance of the Research Achievements

加齢により骨格筋内の遺伝子のDNAメチル化が大きく変わることが知られている。しかしながらそのメカニズムと生理的意義の詳細は不明な点が多い。本研究では、老化による骨格筋の性質変化(筋再生能低下)にDNAメチル化が関与する可能性を検証した。そして、老化に伴うDnmt3aの発現低下によって筋再生能が低下する分子機序を提示した。本研究はサルコペニアの予防改善のための分子標的同定の手がかりとなるものである。

Report

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

    (26 results)

All 2019 2018 Other

All Int'l Joint Research (4 results) Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 6 results) Remarks (2 results)

  • [Int'l Joint Research] University of Camerino(イタリア)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Miami Miller(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Maryland(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Chongqing Medical University(中国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Genistein, daidzein, and resveratrols stimulate PGC-1β-mediated gene expression2019

    • Author(s)
      Uchitomi Ran、Nakai Shiho、Matsuda Rintaro、Onishi Takumi、Miura Shinji、Hatazawa Yukino、Kamei Yasutomi
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 17 Pages: 51-55

    • DOI

      10.1016/j.bbrep.2018.11.009

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Screening dataset of food components that enhance transcriptional activity of PGC1-beta2019

    • Author(s)
      Nakai Shiho、Uchitomi Ran、Matsuda Rintaro、Onishi Takumi、Hatazawa Yukino、Kamei Yasutomi
    • Journal Title

      Data in Brief

      Volume: 23 Pages: 103814-103814

    • DOI

      10.1016/j.dib.2019.103814

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metabolomic analysis of skeletal muscle in aged mice.2019

    • Author(s)
      Uchitomi, R., Hatazawa, Y., Senoo, N., Yoshioka, K., Fujita, M., Shimizu, T., Miura, S., Ono, Y., and Kamei, Y.
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1 Pages: 10425-10425

    • DOI

      10.1038/s41598-019-46929-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metabolomic analysis of C2C12 myoblasts induced by the transcription factor FOXO 12019

    • Author(s)
      Matsuda Rintaro、Uchitomi Ran、Oyabu Mamoru、Hatazawa Yukino、Kamei Yasutomi
    • Journal Title

      FEBS Letters

      Volume: 593 Issue: 12 Pages: 1303-1312

    • DOI

      10.1002/1873-3468.13445

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of long-term physical exercise on skeletal muscles in senescence-accelerated mice (SAMP8)2018

    • Author(s)
      Takigawa Kaho、Matsuda Rintaro、Uchitomi Ran、Onishi Takumi、Hatazawa Yukino、Kamei Yasutomi
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 83 Issue: 3 Pages: 518-524

    • DOI

      10.1080/09168451.2018.1547625

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vitamin D Attenuates FOXO1-Target Atrophy Gene Expression in C2C12 Muscle Cells2018

    • Author(s)
      HIROSE Yuma、ONISHI Takumi、MIURA Shinji、HATAZAWA Yukino、KAMEI Yasutomi
    • Journal Title

      Journal of Nutritional Science and Vitaminology

      Volume: 64 Issue: 3 Pages: 229-232

    • DOI

      10.3177/jnsv.64.229

    • NAID

      130007413183

    • ISSN
      0301-4800, 1881-7742
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epigenetic modulation of Fgf21 in the perinatal mouse liver ameliorates diet-induced obesity in adulthood2018

    • Author(s)
      X Yuan, K Tsujimoto, K Hashimoto, K Kawahori, N Hanzawa, M Hamaguchi, T Seki, M Nawa, T Ehara, Y Kitamura, I Hatada, M Konishi, N Itoh, Y Nakagawa, H Shimano, T Takai-Igarashi, Y Kamei, Y Ogawa.
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 636-636

    • DOI

      10.1038/s41467-018-03038-w

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PGC-1α regulates alanine metabolism in muscle cells.2018

    • Author(s)
      Hatazawa Y, Qian K, Gong DW, Kamei Y.
    • Journal Title

      PLoS One

      Volume: 13(1) Issue: 1 Pages: e0190904-e0190904

    • DOI

      10.1371/journal.pone.0190904

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration2018

    • Author(s)
      Hatazawa Yukino、Ono Yusuke、Hirose Yuma、Kanai Sayaka、Fujii Nobuharu L.、Machida Shuichi、Nishino Ichizo、Shimizu Takahiko、Okano Masaki、Kamei Yasutomi、Ogawa Yoshihiro
    • Journal Title

      The FASEB Journal

      Volume: 32 Issue: 3 Pages: 1452-1467

    • DOI

      10.1096/fj.201700573r

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 骨格筋萎縮における遺伝子発現制御2019

    • Author(s)
      亀井康富
    • Organizer
      日本外科代謝栄養学会 第56回学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Vitamin D attenuates FOXOl-target muscle atrophy gene expression2019

    • Author(s)
      Yasutomi Kamei, Takumi Onishi, Rintaro Matsuda, Ran Uchitomi, Yukino Hatazawa
    • Organizer
      Asian Congress of Nutrition 2019 (ACN2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 老齢マウス骨格筋の代謝変動2019

    • Author(s)
      亀井康富
    • Organizer
      日本基礎老化学会シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration2019

    • Author(s)
      Yasutomi Kamei
    • Organizer
      International Conference on Food Factors 2019 (ICoFF2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 骨格筋機能におけるビタミンDの役割2019

    • Author(s)
      亀井康富
    • Organizer
      第10回 栄養学を志す若手のためのフォーラム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 大豆イソフラボンはPGC-1βを活性化し筋細胞で脂肪酸酸化酵素遺伝子の発現を増加させる2019

    • Author(s)
      亀井康富、中井志帆、内富蘭、畑澤幸乃
    • Organizer
      日本肥満学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 筋萎縮時にDNAメチル化酵素Dnmt3aの低下は筋再生を抑制する2018

    • Author(s)
      亀井康富、畑澤幸乃、小野悠介、岡野正樹、小川佳宏
    • Organizer
      第72回日本栄養・食糧学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 遺伝子改変マウスを用いた骨格筋アミノ酸代謝の解析2018

    • Author(s)
      亀井康富、畑澤幸乃、三浦進司
    • Organizer
      日本筋学会第4回学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 老化促進モデルマウス(SAMP8)の筋機能低下に対する長期的な運動の効果2018

    • Author(s)
      亀井康富、瀧川花穂、松田凛太郎、畑澤幸乃
    • Organizer
      第33回老化促進モデルマウス(SAM)学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] サルコペニアの筋再生低下におけるDNAメチル化制御2018

    • Author(s)
      亀井康富、畑澤幸乃、瀧川花穂、岡野正樹、小野悠介、小川佳宏
    • Organizer
      第39回日本肥満学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Reduced Dnmt3a Increases Gdf5 Expression with Suppressed Satellite Cell Differentiation and Impaired Skeletal Muscle Regeneration2018

    • Author(s)
      亀井康富
    • Organizer
      Asia Pacific Nutrigenomics Nutrigenetics Organisation 2018 Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 京都府立大学大学院生命環境科学研究科分子栄養学研究室

    • URL

      http://nutrition.life.kpu.ac.jp/

    • Related Report
      2019 Annual Research Report
  • [Remarks]

    • URL

      http://nutrition.life.kpu.ac.jp/

    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2021-02-19  

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