• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Anti-senescence therapy for the treatment of age-associated cardiovascular and metabolic diseases

Research Project

Project/Area Number 17390226
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionChiba University

Principal Investigator

MINAMINO Tohru  Chiba University Hospital, Cardiovascular Medicine, 医学部附属病院, 助手 (90328063)

Co-Investigator(Kenkyū-buntansha) KOMURO Issei  Chiba University Graduate School of Medicine, Department of Cardiovascular Science and Medicine, Professor, 大学院医学研究院, 教授 (30260483)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥9,100,000 (Direct Cost: ¥9,100,000)
Fiscal Year 2006: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2005: ¥4,700,000 (Direct Cost: ¥4,700,000)
Keywordsclock gene / telomere / celluar senescence / 血管再生 / サイトカイン / 筋再生 / 日内変動リズム
Research Abstract

Epidemiological studies have shown that age is the dominant risk factor for atherosclerotic cardiovascular diseases. However, the molecular mechanisms underlying the increased risk of such diseases that is conferred by aging remain unclear. Vascular cells have a finite lifespan when cultured in vitro and eventually enter an irreversible growth arrest called "cellular senescence." Human primary cultures derived from the patients with premature aging syndromes, such as Werner syndrome and Bloom syndrome, are known to have shorter lifespan than the cultures from age-matched healthy populations, suggesting a relationship between cellular senescence and aging. We demonstrated the presence of senescent vascular cells in human atherosclerotic lesions but not non-atherosclerotic lesions. Moreover, these cells expressed increased levels of proinflammatory molecules and decreased levels of endothelial nitric oxide synthase, suggesting that cellular senescence in vivo contributes to the pathogene … More sis of human atherosclerosis and vascular aging. We showed a critical role of telomere function in regulating vascular function as well as lifespan of vascular cells. We also found that telomere-independent pathways, such as AngII/Ras and insulin/Akt pathways, were crucial for vascular cell senescence and vascular complication associated with aging.
Aging alters a broad spectrum of physiological, endocrine, and behavioral rhythms. We report here that cellular senescence impairs circadian rhythmicity both in vitro and in vivo. Circadian expression of clock genes in serum-stimulated senescent cells was significantly weaker compared with that in young cells. Introduction of telomerase completely prevented this reduction of clock gene expression associated with senescence. When young cells were implanted into young mice or old mice, the implanted cells were effectively entrained by the circadian rhythm of the recipients. In contrast, the entrainment of implanted senescent cells was markedly impaired. These results suggest that senescence decreases the ability of cells to transmit circadian signals to their clocks and that regulation of clock gene expression may be a novel strategy for the treatment of age-associated impairment of circadian rhythmicity. Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (23 results)

All 2007 2006 2005

All Journal Article (21 results) Book (2 results)

  • [Journal Article] Vascular senescence : Contribution to atherosclerosis2007

    • Author(s)
      Minamino T
    • Journal Title

      Cirs Res 100

      Pages: 15-26

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Vascular senescence : Contribution to atherosclerosis2007

    • Author(s)
      Minamino T
    • Journal Title

      Circ Res. 100

      Pages: 15-26

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Vascular senescence : Contribution to atherosclerosis2007

    • Author(s)
      Minamino T
    • Journal Title

      Circ Res 100

      Pages: 15-26

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cellular senescence impairs circadian expression of clock genes in vitro and in vivo.2006

    • Author(s)
      Kunieda T
    • Journal Title

      Circ Res 98

      Pages: 532-539

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Critical roles of muscle-secreted angiogenic factors in therapeutic neovascularization.2006

    • Author(s)
      Tateno K
    • Journal Title

      Cirs Res 98

      Pages: 1194-1202

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Angiotensin II induces premature senescence of vascular smooth muscle cells and accelerates the development of atherosclerosis via a p21-dependent pathway.2006

    • Author(s)
      Kunieda T
    • Journal Title

      Circulation 114

      Pages: 953-960

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Upregulation of Heat Shock Transcription Factor 1 Plays a Critical Role in Adaptive Cardiac Hypertrophy.2006

    • Author(s)
      Sakamoto M
    • Journal Title

      Circ Res 99

      Pages: 1411-1418

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Regeneration of the endothelium as a novel therapeutic strategy for acute lung injury.2006

    • Author(s)
      Minamino T
    • Journal Title

      J Clin Invest 116

      Pages: 2316-2319

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Cellular senescence impairs circadian expression of clock genes in vitro and in vivo.2006

    • Author(s)
      Kunieda T
    • Journal Title

      Circ Res. 98

      Pages: 532-539

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Critical roles of muscle-secreted angiogenic factors in therapeutic neovascularization.2006

    • Author(s)
      Tateno K
    • Journal Title

      Circ Res. 98

      Pages: 1194-1202

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Upregulation of Heat Shock Transcription Factor 1 Plays a Critical Role in Adaptive Cardiac Hypertrophy.2006

    • Author(s)
      Sakamoto M
    • Journal Title

      Circ Res. 99

      Pages: 1411-1418

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Regeneration of the endothelium as a novel therapeutic strategy for acute lung injury.2006

    • Author(s)
      Minamino T
    • Journal Title

      J Clin Invest. 116

      Pages: 2316-2319

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Antisenescence as a novel therapeutic strategy for vascular aging.2006

    • Author(s)
      Minamino T
    • Journal Title

      Nippon Ronen Igakkai Zasshi. 43

      Pages: 347-350

    • NAID

      10018178576

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Critical roles of muscle-secreted angiogenic factors in therapeutic neovascularization.2006

    • Author(s)
      Tateno K
    • Journal Title

      Circ Res 98

      Pages: 1194-1202

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cellular senescence impairs circadian expression of clock genes In vitro and In vivo.2006

    • Author(s)
      Kunieda T
    • Journal Title

      Circ Res 98

      Pages: 532-539

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Phosphatidylinositol 3-Kinase-Akt Pathway Plays a Critical Role in Early Cardiomyogenesis by Regulating Canonical Wnt Signaling.2005

    • Author(s)
      Naito AT
    • Journal Title

      Circ Res 22

      Pages: 144-151

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] G-CSF prevents cardiac Remodeling after myocardial infarction by activating Jak/Stat in cardiomyocytes.2005

    • Author(s)
      Harada M
    • Journal Title

      Nat Med 11

      Pages: 305-311

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Phosphatidylinositol 3-Kinase-Akt Pathway Plays a Critical Role in Early Cardiomyogenesis by Regulating Canonical Wnt Signaling.2005

    • Author(s)
      Naito AT
    • Journal Title

      Cirs Res. 22

      Pages: 144-151

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] G-CSF prevents cardiac Remodeling after myocardial infarction by activating Jak/Stat in cardiomyocytes.2005

    • Author(s)
      Harada M
    • Journal Title

      Nat Med. 11

      Pages: 305-311

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Phosphatidylinositol 3-kinase-Akt pathway plays a critical role in earl cardiomyogenesis by regulating canonical Wnt signaling.2005

    • Author(s)
      Naito AT
    • Journal Title

      Circ Res 22

      Pages: 144-151

    • Related Report
      2005 Annual Research Report
  • [Journal Article] G-CSF prevents cardiac remodeling after myocardial infarction by activating Jak/Stat in cardiomyocytes.2005

    • Author(s)
      Harada M
    • Journal Title

      Nat Med 11

      Pages: 305-311

    • Related Report
      2005 Annual Research Report
  • [Book] 血管壁細胞の老化2006

    • Author(s)
      南野 徹
    • Total Pages
      8
    • Publisher
      日本老年医学会
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 血管壁細胞の老化2006

    • Author(s)
      南野徹
    • Total Pages
      8
    • Publisher
      日本老年医学会
    • Related Report
      2006 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi