Potential mechanisms and therapeutic strategies of sarcopenia

• Project/Area Number: 22390143
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General internal medicine (including Psychosomatic medicine)
• Research Institution: Nagoya 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: ¥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.

Research Products

• [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 cells (2014)
  • 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
  • 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
• [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
  • 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
  • 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
  • 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
  • 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
• [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
  • 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
  • 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
• [Journal Article] Role for cysteine protease cathepsins in heart disease: focus on biology and mechanisms with clinical implication (2012)
  • Author(s): Cheng XW
  • Journal Title: Circulation Volume: 125 Pages: 1551-1562
  • Peer Reviewed
• [Journal Article] Osteoarthritic change is delayed in a Ctsk-knockout mouse model of osteoarthritis (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Cysteine protease cathepsins in atherosclerosis-based vascular disease and its complications (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Angiotensin type 1 receptor blocker reduces intimal neovascularization and plaque growth in apolipoprotein E-deficient mice (2011)
  • 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
  • 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
  • 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 age (2010)
  • 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
  • Peer Reviewed
• [Journal Article] Ca2+ channel blocker benidipine promotes coronary angiogenesis and reduces both left ventricular diastolic stiffness and mortality in hypertensive rats (2010)
  • 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
  • Peer Reviewed
• [Journal Article] AT1 Blockade Attenuates Atherosclerotic Plaque Destabilization Accompanied by the Suppression of Cathepsin S Activity in ApoE-Deficient Mice (2010)
  • 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
  • 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
• [Presentation] サルコペニアとは?そのoverview (2013)
  • 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
• [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
• [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
• [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