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Understanding of the mechansism for clearance of senescent cells

Research Project

Project/Area Number 16K15238
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Johmura Yoshikazu  東京大学, 医科学研究所, 助教 (40616322)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords老化 / 細胞周期 / 脂質 / がん / 免疫 / クリアランス / 細胞膜 / 癌
Outline of Final Research Achievements

Accumulation of senescent cells has been proposed to be involved in various age-associated pathologies, but molecular basis underlying the accumulation has ramained unknown. In the present study, we found that ATP11C, a fllipase for phosphatidylserine,is down-regulatred in senescent cells.However, overexpression and down-regulation of ATP11-related genes do not affet the expression of phosphatidylserine on senescent cell surface.Furthermore, Inhibition of calcium signaling, an essential component for ATP11 fllipase, also does not affect the expression of phosphatidylserine on senescent cell surface. These results strongly suggest that there is an unique mechanism for clearance of senescent cells

Academic Significance and Societal Importance of the Research Achievements

細胞老化は、恒久的増殖停止を特徴とする細胞表現で、抗腫瘍機構として作用する。最近、早老症モデルマウスから老化細胞を人工的に除去すると、「老い」の進行が遅延することが報告され、細胞老化が個体老化の主な原因であることが示された。しかし、加齢に伴い老化細胞が蓄積する機構は不明である。本研究では、貪食シグナルとなるホスファチジルセリンが老化細胞の膜表面に露出する事を見出したが、未知のメカニズムにより制御されることが分かった。今後、その詳細なメカニズムを解明することで、老化細胞の貪食が個体老化や加齢性疾病発症に与える影響を明らかにできると考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 2017 2016

All Journal Article (10 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 10 results,  Open Access: 10 results,  Acknowledgement Compliant: 2 results) Presentation (1 results) (of which Invited: 1 results) Book (2 results)

  • [Journal Article] Cdk1-mediated DIAPH1 phosphorylation maintains metaphase cortical tension and inactivates the spindle assembly checkpoint at anaphase.2019

    • Author(s)
      Nishimura K, Johmura Y, Deguchi K, Jiang Z, Uchida KSK, Suzuki N, Shimada M, Chiba Y, Hirota T, Yoshimura SH, Kono K, Nakanishi M.
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41467-019-08957-w

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Isozyme-Specific Role of SAD-A in Neuronal Migration During Development of Cerebral Cortex2018

    • Author(s)
      Nakanishi Keiko、Niida Hiroyuki、Tabata Hidenori、Ito Tsuyoshi、Hori Yuki、Hattori Madoka、Johmura Yoshikazu、Yamada Chisato、Ueda Takashi、Takeuchi Kosei、Yamada Kenichiro、Nagata Koh-ichi、Wakamatsu Nobuaki、Kishi Masashi、Pan Y Albert、Ugawa Shinya、Shimada Shoichi、Sanes Joshua R、Higashi Yujiro、Nakanishi Makoto
    • Journal Title

      Cerebral Cortex

      Volume: 160 Issue: 9 Pages: 721-721

    • DOI

      10.1093/cercor/bhy253

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fbxo22-mediated KDM4B degradation determines selective estrogen receptor modulator activity in breast cancer.2018

    • Author(s)
      Johmura Y, Maeda I, Suzuki N, Wu W, Goda A,Morita M, Yamaguchi K, Yamamoto M, Nagasawa S, Kojima Y, Tsugawa K, Inoue N, Miyoshi Y, Osako T Akiyama F, Maruyama R, Inoue JI, Fukukawa Y, Ohta T, Nkanishi M.
    • Journal Title

      J Clin Invest.

      Volume: 128 Issue: 12 Pages: 5603-5619

    • DOI

      10.1172/jci121679

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The G2 checkpoint inhibitor CBP-93872 increases the sensitivity of colorectal and pancreatic cancer cells to chemotherapy.2017

    • Author(s)
      Iwata T, Uchino T, Koyama A, Johmura Y, Koyama K, Saito T, Ishiguro S, Arikawa T, Komatsu S, Miyachi M, Sano T, Nakanishi M, Shimada M.
    • Journal Title

      Plos one

      Volume: 12 Issue: 5 Pages: 1-13

    • DOI

      10.1371/journal.pone.0178221

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Usp7-dependent histone H3 deubiquitylation regulates maintenance of DNA methylation.2017

    • Author(s)
      Yamaguchi L, Nishiyama A, Misaki T, Johmura Y, Ueda J, Arita K, Nagao K, Obuse C, Nakanishi M
    • Journal Title

      Scientific reports

      Volume: 7 Issue: 1 Pages: 1-12

    • DOI

      10.1038/s41598-017-00136-5

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A combination of genetic and biochemical analyses for the diagnosis of PI3K-AKT-mTOR pathway-associated megalencephaly.2017

    • Author(s)
      Negishi Y, Miya F, Hattori A, Johmura Y, Nakagawa M, Ando N, Hori I, Togawa T, Aoyama K, Ohashi K, Fukumura S, Mizuno S, Umemura A, Kishimoto Y, Okamoto N, Kato M, Tsunoda T, Yamasaki M, Kanemura Y, Kosaki K, Nakanishi M, Saitoh S.
    • Journal Title

      BMC Med Genet.

      Volume: 18 Issue: 1 Pages: 4-4

    • DOI

      10.1186/s12881-016-0363-6

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HP1 regulates the localization of FANCJ at sites of DNA double-strand breaks.2016

    • Author(s)
      Wu W, Togashi Y, Johmura Y, Miyoshi Y, Nobuoka S, Nakanishi M, Ohta T.
    • Journal Title

      Cancer Sci.

      Volume: 107 Issue: 10 Pages: 1406-1415

    • DOI

      10.1111/cas.13008

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Multiple facets of p53 in senescence induction and maintenance.2016

    • Author(s)
      Johmura Y, Nakanishi M.
    • Journal Title

      Cancer Sci.

      Volume: 107 Issue: 11 Pages: 1550-1555

    • DOI

      10.1111/cas.13060

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Defective DNA repair increases susceptibility to senescence through extension of Chk1-mediated G2 checkpoint activation.2016

    • Author(s)
      Johmura Y, Yamashita E, Shimada M, Nakanishi K, Nakanishi M.
    • Journal Title

      Sci Rep.

      Volume: - Issue: 1 Pages: 31194-31194

    • DOI

      10.1038/srep31194

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural and functional insights into IZUMO1 recognition by JUNO in mammalian fertilization.2016

    • Author(s)
      Kato K, Satouh Y, Nishimasu H, Kurabayashi A, Morita J, Fujihara Y, Oji A, Ishitani R, Ikawa M, Nureki O.
    • Journal Title

      Nat Commun.

      Volume: 7 Issue: 1 Pages: 12198-12198

    • DOI

      10.1038/ncomms12059

    • NAID

      120006957420

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Challenging boundaries in healthspan: Mechanisms of cellular senescence induction and maintenance2019

    • Author(s)
      Yoshikazu Johmura
    • Organizer
      6th Symposium of the Smart-Aging Research Center
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] . アンチ・エイジング医学2018

    • Author(s)
      城村由和、中西真
    • Total Pages
      7
    • Publisher
      メディカルレビュー社
    • ISBN
      9784779221606
    • Related Report
      2018 Annual Research Report
  • [Book] 実験医学2017

    • Author(s)
      城村由和、中西真
    • Total Pages
      6
    • Publisher
      羊土社
    • ISBN
      9784758101677
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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