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Gene regulatory network of supercentenarians reveals resilience agains hypoxia stress

Research Project

Project/Area Number 26640126
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Medical genome science
Research InstitutionNational Institute of Genetics

Principal Investigator

Inoue Ituro  国立遺伝学研究所, 総合遺伝研究系, 教授 (00192500)

Research Collaborator HIROSE Nobuyoshi  
ARAI Yasumichi  
Casingal Cristine R.  
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords超長寿者 / ミトコンドリア変異 / 次世代シーケンサー / ヒトゲノム配列再解析
Outline of Final Research Achievements

Supercentenarians (SC, ages 110-119 years) are individuals who exhibit exceptional longevity (EL). EL is rare and is thought to be a combined influence of environmental and genetic factors, where genetic contribution is approximately 20-30%. It is likely that the molecular mechanisms of EL are shared with those of healthy aging - being free of age-related diseases and functionally independent in daily life activities.
To explore the genetic contributions of SC, we utilized RNA sequencing and iPSC technology to differentiate gene expression profiles of SC from the control (CTRL) subjects in the hypoxia condition. iPSC-EC from SC has the following characteristics: (1) a more robust stress response mechanism; (2) responds faster in the presence of stress; (3) shows resilience to stress; (4) and exhibits transcriptional stability. These characteristics might contribute to exceptional longevity.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (8 results)

All 2016 2015

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus.2016

    • Author(s)
      Nakaoka H, Gurumurthy A, Hayano T, Ahmadloo S, Omer WH, Yoshihara K, Yamamoto A, Kurose K, Enomoto T, Akira S, Hosomichi K,, Inoue I.
    • Journal Title

      PLoS Genet.

      Volume: 1 Issue: 4 Pages: 1-23

    • DOI

      10.1371/journal.pgen.1005893

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel kinase fusion transcripts found in endometrial cancer.2015

    • Author(s)
      Tamura R, Yoshihara K, Yamawaki K, Suda K, Ishiguro T, Adachi S, Okuda S, Inoue I, Verhaak RG, Enomoto T.
    • Journal Title

      Sci Rep.

      Volume: 5 Issue: 1 Pages: 18657-18657

    • DOI

      10.1038/srep18657

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of novel exonic mobile element insertions in epithelial ovarian cancers.2015

    • Author(s)
      Hayano,T., Yamada,S., Hosomichi,K., Nakaoka,H., Yoshihara,K., Adachi.S. Kashima,K., Tanaka, K and Enomoto,T.& Inoue,I.
    • Journal Title

      Human Genome Variation

      Volume: 2 Issue: 1 Pages: 15030-15030

    • DOI

      10.1038/hgv.2015.30

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The impact of next-generation sequencing technologies on HLA research.2015

    • Author(s)
      Hosomichi K, Shiina T, Tajima A, Inoue I.
    • Journal Title

      Journal of human genetics

      Volume: 60 Issue: 11 Pages: 665-673

    • DOI

      10.1038/jhg.2015.102

    • NAID

      40020655134

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distribution of HLA haplotypes across Japanese Archipelago: similarity, difference and admixture.2015

    • Author(s)
      Nakaoka H, Inoue I.
    • Journal Title

      Journal of human genetics

      Volume: 60 Issue: 11 Pages: 683-690

    • DOI

      10.1038/jhg.2015.90

    • NAID

      40020655147

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Unique characteristics of the Ainu population in Northern Japan2015

    • Author(s)
      Jinam TA, Kanzawa-Kiriyama H, Inoue I, Tokunaga K, Omoto K, Saitou N
    • Journal Title

      Journal of Human Genetics

      Volume: 60 Issue: 10 Pages: 565-571

    • DOI

      10.1038/jhg.2015.79

    • NAID

      40020621361

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aggregation of rare/low-frequency variants of the mitochondria respiratory chain-related proteins in rheumatoid arthritis patients.2015

    • Author(s)
      Mitsunaga S, Hosomichi K, Okudaira Y, Nakaoka H, Suzuki Y, Kuwana M, Sato S, Kaneko Y, Homma Y, Oka A, Shiina T, Inoko H, Inoue I.
    • Journal Title

      J Hum Genet

      Volume: 60 Issue: 8 Pages: 449-454

    • DOI

      10.1038/jhg.2015.50

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] RNA sequencing reveals stress responses of iPSC-derived endothelial cells isolated from peripheral blood mononuclear cells of supercentenarians2016

    • Author(s)
      Cristine R. Casingal
    • Organizer
      The 13th International Congress of Human Genetics
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2016-04-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research

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Published: 2014-04-04   Modified: 2017-05-10  

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