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Potential mechanisms and therapeutic strategies of sarcopenia

Research Project

Project/Area Number 22390143
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General internal medicine (including Psychosomatic medicine)
Research InstitutionNagoya University

Principal Investigator

KUZUYA Masafumi  名古屋大学, 医学(系)研究科(研究院), 教授 (10283441)

Co-Investigator(Renkei-kenkyūsha) CHENG Xian Wu  名古屋大学, 医学系研究科, 特任准教授 (30378228)
Project Period (FY) 2010-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2012: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2010: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords老化 / サルコペニア / 動物 / 運動 / 骨髄移植 / 老化促進マウス / C2C12細胞 / beta-Hydroxy-beta-Methylbutyrate
Research Abstract

To examine the effect of bone marrow stem cells as well as exercise on the age-associated skeletal muscle atrophy and weakness (sarcopenia), senescence-accelerated-prone mouse (SAMP10) were transplanted with bone marrow of wild-type (C57BL/6) at 8 weeks of age. Control non-transplant and transplant SMAP10 were randomly assigned to 2 groups with or without exercise training (from 25 weeks of age). At 40 weeks of age, muscle weight, endurance capacity, and the tissue biochemical analysis were carried out.
These studies provide the evidences that the bone marrow-derived stem cells differentiate into skeletal muscle cells. Bone marrow transplantation of wild type mice improves the age-associated skeletal muscle atrophy and weakness (sarcopenia), suggesting that aging of bone marrow cells may contribute to the cause of sarcopenia of SAMP10. In addition, exercise can prevent sarcopenia through the prevention of muscle protein degradation and mitochondrial activation in SAMP10.

Report

(5 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (23 results)

All 2014 2013 2012 2011 2010 Other

All Journal Article (18 results) (of which Peer Reviewed: 15 results,  Open Access: 2 results) Presentation (5 results)

  • [Journal Article] β-Hydroxy-β- methylbutyrate facilitates PI3K/Aktdependent mammalian target of rapamycin and FoxO1/3a phosphorylations and alleviates tumor necrosis factor α/ interferon γ-induced MuRF-1 expression in C2C12 cells2014

    • Author(s)
      Kimura K, Cheng XW, Inoue A, Hu L, Koike T, Kuzuya M
    • Journal Title

      Nutr Res

      Volume: 34(4) Issue: 4 Pages: 368-74

    • DOI

      10.1016/j.nutres.2014.02.003

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] サルコぺニアー成因と対策病因 原発生ならびに二次性サルコぺニアと動物モデル2014

    • Author(s)
      葛谷 雅文
    • Journal Title

      医学のあゆみ

      Volume: 248(9) Pages: 696-700

    • Related Report
      2013 Final Research Report
  • [Journal Article] Cathepsin K-Mediated Notch1 Activation Contributes to Neovascularisation in Response to Hypoxia.2014

    • Author(s)
      Jiang H, Cheng XW, Shi GP, Hu L, Inoue A, Yamamura Y, Wu H, Takeshita K, Li X, Huang Z, Song H, Asai M, Hao CN, Unno K, Koike T, Oshida Y, Okumura K, Murohara T, Kuzuya M.
    • Journal Title

      Nature Communications.

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] β-Hydroxy-β-methylbutyrate facilitates PI3K/Akt-depednet mTOR and FoxO1/3 phosphorylations and alleviates TNF-1α/IFN-γ-induced MuRF expression in C2C12 Cells.2014

    • Author(s)
      Kimura K, Cheng XW, Inoue A, Hu L, Koike T ,Kuzuya M.
    • Journal Title

      Nutrition Research.

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endothelial cellular senescence is inhibited by liver X receptor activation with an additional mechanism for its atheroprotection in diabetes.2014

    • Author(s)
      Hayashi T, Kotani H, Yamaguchi T, Taguchi K, Iida M, Ina K, Maeda M, Kuzuya M, Hattori Y, Ignarro LJ.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 111(3) Issue: 3 Pages: 1168-1173

    • DOI

      10.1073/pnas.1322153111

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cathepsin K activity controls injury-related vascular repair in mice.2014

    • Author(s)
      Hu L, Cheng XW, Song H, Inoue A, Jiang H, Li X, Shi GP, Kozawa E, Okumura K, Kuzuya M.
    • Journal Title

      Hypertension.

      Volume: 63(3) Issue: 3 Pages: 607-615

    • DOI

      10.1161/hypertensionaha.113.02141

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] サルコペニアと栄養2013

    • Author(s)
      葛谷 雅文
    • Journal Title

      腎と骨代謝

      Volume: 26(2) Pages: 135-141

    • NAID

      130005067263

    • Related Report
      2013 Final Research Report
  • [Journal Article] Circulating cathepsin K as a potential novel biomarker of coronary artery disease.2013

    • Author(s)
      Cheng XW, Kikuchi R, Ishii H, Yoshikawa D, Hu L, Takahashi R, Shibata R, Ikeda N, Kuzuya M, Okumura K, Murohara T.
    • Journal Title

      Atherosclerosis.

      Volume: 228(1) Issue: 1 Pages: 211-216

    • DOI

      10.1016/j.atherosclerosis.2013.01.004

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Matrix metalloproteinase-2 deficiency impairs aortic atherosclerotic calcification in ApoE-deficient mice.2013

    • Author(s)
      Sasaki T, Nakamura K, Sasada K, Okada S, Cheng XW, Suzuki T, Murohara T, Sato K, Kuzuya M.
    • Journal Title

      Atherosclerosis.

      Volume: 227(1) Issue: 1 Pages: 43-50

    • DOI

      10.1016/j.atherosclerosis.2012.12.008

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] サルコペニア予防・治療と栄養の考え方(Q&A)2012

    • Author(s)
      葛谷 雅文
    • Journal Title

      医事新報

      Volume: No. 4600 56-57

    • Related Report
      2013 Final Research Report
  • [Journal Article] Role for cysteine protease cathepsins in heart disease: focus on biology and mechanisms with clinical implication2012

    • Author(s)
      Cheng XW
    • Journal Title

      Circulation

      Volume: 125 Pages: 1551-1562

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Osteoarthritic change is delayed in a Ctsk-knockout mouse model of osteoarthritis2012

    • Author(s)
      Kozawa E, Nishida Y, Cheng XW, Urakawa H, Arai E, Futamura N, Shi GP, Kuzuya M, Hu L, Sasaki T, Ishiguro N
    • Journal Title

      Arthritis Rheum

      Volume: 64 Issue: 2 Pages: 454-64

    • DOI

      10.1002/art.33398

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cysteine protease cathepsins in atherosclerosis-based vascular disease and its complications2011

    • Author(s)
      Cheng XW, Huang Z, Kuzuya M, Okumura K, Murohara T
    • Journal Title

      Hypertension

      Volume: 58 Issue: 6 Pages: 978-86

    • DOI

      10.1161/hypertensionaha.111.180935

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiotensin type 1 receptor blocker reduces intimal neovascularization and plaque growth in apolipoprotein E-deficient mice2011

    • Author(s)
      Cheng XW, Song H, Sasaki T, Hu L, Inoue A, Bando YK, Shi GP, Kuzuya M, Okumura K, Murohara T
    • Journal Title

      Hypertension

      Volume: 57 Issue: 5 Pages: 981-9

    • DOI

      10.1161/hypertensionaha.110.168385

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Matrix Metalloproteinase-2 (MMP-2) Regulates the Expression of Tissue Inhibitor of MMP-2 (TIMP-2)2010

    • Author(s)
      Kimura K, Cheng XW, Nakamura K, Inoue A, Hu L, Song H, Okumura K, Iguchi A, Murohara T, Kuzuya M
    • Journal Title

      Clin Exp Pharmacol Physiol

      Volume: 37 Pages: 1096-1101

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exercise training stimulates ischemia-induced neovascularization via phosphatidylinositol 3-kinase/Akt-dependent hypoxia-induced factor-1 alpha reactivation in mice of advanced age2010

    • Author(s)
      Cheng XW, Kuzuya M, Kim W, Song H, Hu L, Inoue A, Nakamura K, Di Q, Sasaki T, Tsuzuki M, Shi GP, Okumura K, Murohara T
    • Journal Title

      Circulation

      Volume: 122 Pages: 707-716

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ca2+ channel blocker benidipine promotes coronary angiogenesis and reduces both left ventricular diastolic stiffness and mortality in hypertensive rats2010

    • Author(s)
      Nishizawa T, Cheng XW, Jin Z, Obata K, Nagata K, Hirashiki A, Sasaki T, Noda A, Takeshita K, Izawa H, Shi GP, Kuzuya M, Okumura K, Murohara T
    • Journal Title

      J Hypertens

      Volume: 28 Pages: 1515-1526

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] AT1 Blockade Attenuates Atherosclerotic Plaque Destabilization Accompanied by the Suppression of Cathepsin S Activity in ApoE-Deficient Mice2010

    • Author(s)
      Sasaki T, Kuzuya M, Nakamura K, Cheng XW, Hayashi T, Song H, Hu L, Okumura K, Murohara T, Iguchi A, Sato K
    • Journal Title

      Atherosclerosis

      Volume: 210 Pages: 430-437

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] C2C12細胞におけるタンパク分解に対するHMB の効果atrogin-1,MuRFの発現とその制御に関して2014

    • Author(s)
      木村 薫, 成 憲武, 井上 愛子, 胡 麗娜, 葛谷 雅文
    • Organizer
      第29回日本静脈経腸栄養学会学術集会
    • Place of Presentation
      横浜市パシフィコ横浜
    • Year and Date
      2014-02-27
    • Related Report
      2013 Final Research Report
  • [Presentation] サルコペニアとは?そのoverview2013

    • Author(s)
      葛谷 雅文
    • Organizer
      第23回日本老年医学会九州地方会シンポジウム 「オムニバスシンポジオウム : 高齢者サルコペニアの病態と治療」
    • Place of Presentation
      福岡市 九州大学医学部百年講堂
    • Year and Date
      2013-03-09
    • Related Report
      2013 Final Research Report
  • [Presentation] シンポジウム高齢者の「サルコペニア」ならびに「虚弱」とその対策2012

    • Author(s)
      葛谷 雅文
    • Organizer
      第54回日本老年医学会学術集会
    • Place of Presentation
      東京都千代田区 東京国際フォーラム
    • Year and Date
      2012-06-28
    • Related Report
      2013 Final Research Report
  • [Presentation] サルコペニア診断基準とリスク要因の検討2012

    • Author(s)
      岡田希和子
    • Organizer
      第54回日本老年医学会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] 地域在住高齢者のサルコペニアと身体計測及び生活・運動機能の関係について

    • Author(s)
      白石成明
    • Organizer
      第54回日本老年医学会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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