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Glycobiology-based cellular slow cycling for the development of anti-ageing drugs

Research Project

Project/Area Number 22K19712
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research InstitutionKagawa University

Principal Investigator

Akira Nishiyama  香川大学, 医学部, 教授 (10325334)

Project Period (FY) 2022-06-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords老化 / 細胞周期 / 希少糖
Outline of Research at the Start

近年、老化を「細胞で生じる疾患」と捉え、細胞老化 (cellular senescence) の分子機構の解明が世界レベルで進んでいるが、有効な老化予防法は開発されていない。これに対して申請者は最近、単糖類である希少糖・ D-alloseが、ヒト細胞周期を停止(静止)させることなく、周期速度を減速させることを発見した。そこで本研究では、香川大学の持つグリコバイオロジーの知と技術を集結させ、D-allose によって生じる「細胞周期の減速(細胞スローサイクリング)」が、細胞老化を抑制することを細胞・生体レベルで実証し、全く新しい視点の老化予防薬開発につなげることに挑戦する。

Outline of Final Research Achievements

In this study, we attempted to demonstrate that the 'cell cycle deceleration' caused by the monosaccharide D-allose, a rare sugar, inhibits cellular senescence, thereby offering a new perspective for the development of anti-aging drugs. As a result, we proved that D-allose slows down the cultured human cell cycle without arresting it, and applied for a patent. Furthermore, we identified D-allose uptake into the cell and its effects on intracellular energy metabolism in mitochondrial respiration and glycolysis. The results of this research provide data strongly suggesting a preventive effect of D-allose on cellular aging via 'cellular slow cycling' at the cellular and biological level, which should lead to the development of a new concept of anti-aging drugs.

Academic Significance and Societal Importance of the Research Achievements

近年、老化を「細胞レベルで生じる疾患」と捉え、細胞老化 (cellular senescence) の分子機構の解明が世界レベルで進んでいるものの、有効な老化予防法は開発されていない。これに対して本研究は、単糖類である希少糖・D-allose によって生じる「細胞周期の減速(細胞スローサイクリング)」が、細胞老化を抑制することを実証したものであることから、全く新しい視点の老化予防薬開発につなげるきっかけとなるものであると考えられ、大きな学術的意義と社会的意義を持つ研究成果であると考えられる。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (20 results)

All 2023 2022 Other

All Int'l Joint Research (1 results) Journal Article (12 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] University of California, Merced(米国)

    • Related Report
      2022 Research-status Report
  • [Journal Article] Possible contribution of phosphate to the pathogenesis of chronic kidney disease in dolphins.2023

    • Author(s)
      Nourin Jahan, Hiroyuki Ohsaki, Kiyoko Kaneko, Asadur Rahman, Takeshi Nishiyama, Makoto Koizumi, Shuichiro Yamanaka, Kento Kitada, Yuki Sugiura, Kenji Matsui, Takashi Yokoo, Takayuki Hamano, Makoto Kuro-O, Takuya Itou, Miwa Suzuki, Keiichi Ueda, Akira Nishiyama
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 5161-5161

    • DOI

      10.1038/s41598-023-32399-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possible renoprotective mechanisms of SGLT2 inhibitors.2023

    • Author(s)
      Akira Nishiyama, Kento Kitada
    • Journal Title

      Frontiers in Medicine

      Volume: 10 Pages: 1115413-1115413

    • DOI

      10.3389/fmed.2023.1115413

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antiproliferative effects of D-allose associated with reduced cell division frequency in glioblastoma2023

    • Author(s)
      Suzuki Kenta、Ogawa Daisuke、Kanda Takahiro、Fujimori Takeshi、Shibayama Yuki、Rahman Asadur、Ye Juanjuan、Ohsaki Hiroyuki、Akimitsu Kazuya、Izumori Ken、Tamiya Takashi、Nishiyama Akira、Miyake Keisuke
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 19515-19515

    • DOI

      10.1038/s41598-023-46796-4

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Klotho supplementation reverses renal dysfunction and interstitial fibrosis in remnant kidney.2023

    • Author(s)
      Takenaka Tsuneo、Hasan Arif、Marumo Takeshi、Inoue Tsutomu、Miyazaki Takashi、Suzuki Hiromichi、Kurosaki Yoshifumi、Ishii Naohito、Nishiyama Akira、Hayashi Matsuhiko
    • Journal Title

      Kidney and Blood Pressure Research

      Volume: 1 Issue: 1 Pages: 1-1

    • DOI

      10.1159/000530469

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Simultaneous SGLT2 inhibition and caloric restriction improves insulin resistance and kidney function in OLETF rats2023

    • Author(s)
      Cornejo Manuel A.、Jardines Eira、Nishiyama Akira、Nakano Daisuke、Ortiz Rudy M.
    • Journal Title

      Molecular and Cellular Endocrinology

      Volume: 560 Pages: 111811-111811

    • DOI

      10.1016/j.mce.2022.111811

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Glucose emission spectra through mid-infrared passive spectroscopic imaging of the wrist for non-invasive glucose sensing2022

    • Author(s)
      Kitazaki Tomoya、Morimoto Yusuke、Yamashita So、Anabuki Daichi、Tahara Shiori、Nishiyama Akira、Wada Kenji、Ishimaru Ichiro
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 20558-20558

    • DOI

      10.1038/s41598-022-25161-x

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exposing intracellular molecular changes during the differentiation of human-induced pluripotent stem cells into erythropoietin-producing cells using Raman spectroscopy and imaging2022

    • Author(s)
      Ishigaki M, Hitomi H, Ozaki Y, Nishiyama A.
    • Journal Title

      Sci Rep.

      Volume: 12 Issue: 1 Pages: 20454-20454

    • DOI

      10.1038/s41598-022-24725-1

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Angiotensin receptor blockade with olmesartan alleviates brain pathology in obese <scp>OLETF</scp> rats2022

    • Author(s)
      Rodriguez‐Ortiz Carlos J.、Thorwald Max A.、Rodriguez Ruben、Mejias‐Ortega Marina、Kieu Zanett、Maitra Neilabjo、Hawkins Charlesice、Valenzuela Joanna、Peng Marcus、Nishiyama Akira、Ortiz Rudy M.、Kitazawa Masashi
    • Journal Title

      Clinical and Experimental Pharmacology and Physiology

      Volume: 50 Issue: 3 Pages: 228-237

    • DOI

      10.1111/1440-1681.13738

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Contributions of renal water loss and skin water conservation to blood pressure elevation in spontaneously hypertensive rats2022

    • Author(s)
      Ogura Takahiro、Kitada Kento、Morisawa Norihiko、Fujisawa Yoshihide、Kidoguchi Satoshi、Nakano Daisuke、Kobara Hideki、Masaki Tsutomu、Titze Jens、Nishiyama Akira
    • Journal Title

      Hypertension Research

      Volume: 46 Issue: 1 Pages: 32-39

    • DOI

      10.1038/s41440-022-01044-6

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association of Antihypertensive Effects of Esaxerenone with the Internal Sodium Balance in Dahl Salt-Sensitive Hypertensive Rats2022

    • Author(s)
      Hattori Mai、Rahman Asadur、Kidoguchi Satoshi、Jahan Nourin、Fujisawa Yoshihide、Morisawa Norihiko、Ohsaki Hiroyuki、Kobara Hideki、Masaki Tsutomu、Hossain Akram、Steeve Akumwami、Nishiyama Akira
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 16 Pages: 8915-8915

    • DOI

      10.3390/ijms23168915

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blood pressure adaptation in vertebrates: comparative biology2022

    • Author(s)
      Nishiyama Akira、Kitada Kento、Suzuki Miwa
    • Journal Title

      Kidney International

      Volume: 102 Issue: 2 Pages: 242-247

    • DOI

      10.1016/j.kint.2022.03.032

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tolvaptan induces body fluid loss and subsequent water conservation in normal rats2022

    • Author(s)
      Kidoguchi Satoshi、Kitada Kento、Fujisawa Yoshihide、Nakano Daisuke、Yokoo Takashi、Titze Jens、Nishiyama Akira
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 149 Issue: 3 Pages: 115-123

    • DOI

      10.1016/j.jphs.2022.04.008

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 神経膠芽腫に対する希少糖D-alloseの効果とエネルギー代謝との関連2023

    • Author(s)
      西山 成、菅田 峻光、北田 研人、ラフマン アサダ、三宅 啓介.
    • Organizer
      第143回日本薬理学会近畿部会
    • Related Report
      2023 Annual Research Report
  • [Presentation] New salt concept and significance of MR inhibition2022

    • Author(s)
      Nishiyama A.
    • Organizer
      The 29th Scientific Meeting of the International Society of Hypertension.
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Onco-Hypertension.2022

    • Author(s)
      Nishiyama A.
    • Organizer
      International SHR meeting 2022.
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 香川大学医学部薬理学ホームページ

    • URL

      http://www.kms.ac.jp/%7Eyakuri/index.html

    • Related Report
      2023 Annual Research Report
  • [Remarks] 香川大学医学部薬理学ホームページ

    • URL

      http://www.kms.ac.jp/%7Eyakuri/

    • Related Report
      2022 Research-status Report
  • [Patent(Industrial Property Rights)] 細胞増殖遅延剤、それを含む化粧品、及び細胞増殖を遅延させる方法2023

    • Inventor(s)
      西山 成、他
    • Industrial Property Rights Holder
      西山 成、他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2023
    • Related Report
      2023 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 細胞増殖遅延剤、それを含む化粧品、及び細胞増殖を 遅延させる方法2022

    • Inventor(s)
      西山成
    • Industrial Property Rights Holder
      西山成
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-004569
    • Filing Date
      2022
    • Related Report
      2022 Research-status Report

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Published: 2022-07-05   Modified: 2025-01-30  

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