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

Elucidation of aging phenomenom based on the assessment of tRNA aminoacylation.

Research Project

Project/Area Number 22K19414
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 48:Biomedical structure and function and related fields
Research InstitutionOsaka University (2023-2024)
National Institutes of Biomedical Innovation, Health and Nutrition (2022)

Principal Investigator

Kimura Tomonori  大阪大学, 大学院医学系研究科, 招へい准教授 (00631300)

Co-Investigator(Kenkyū-buntansha) 塚本 悠介  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 難治性疾患研究開発・支援センター, 特任研究員 (60838944)
Project Period (FY) 2022-06-30 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2024: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordstRNA / D-アミノ酸 / D-アラニン / グルタミン / チャージ / 概日リズム / 糖代謝 / 生活習慣病 / 加齢 / アミノ酸 / 腎臓病 / キラリティ / 代謝 / トランスファーRNA / タンパク質 / 老化 / 疾患 / アミノアシル化
Outline of Research at the Start

tRNAは細胞内タンパク質翻訳の際にアミノ酸を供給する分子であるが、tRNAにアミノ酸がついているかどうか(アミノアシル化状態)を評価するのが困難であり研究開発が進んでいなかった。本研究開発において、我々はtRNAのチャージ率(アミノアシル化率)を網羅的に評価する手法を開発し、この技術を基に、tRNAチャージ率の老化や難病における意義について検討する。

Outline of Final Research Achievements

tRNA is a crucial molecule involved in protein synthesis, transporting amino acids. This research revealed that the charging rate of tRNA reflects the nutritional status of cells and serves as a starting point for intracellular signaling. Notably, the charging rate of tRNA(Gln) reflects the intracellular glutamine concentration, and when it decreases, a mechanism is activated to maintain the charging rate.
On the other hand, D-alanine is a type of D-amino acid present in trace amounts in organisms, and it has been found to contribute to the regulation of circadian rhythms and the maintenance of homeostasis in the body. D-alanine influences circadian rhythms, which are involved in various biological responses such as carbohydrate metabolism, immune responses, and aging. Specifically, D-alanine controls the production of carbohydrates to keep blood sugar levels stable.

Academic Significance and Societal Importance of the Research Achievements

tRNAとD-アラニンの役割解明は、生命の根源的なメカニズムを理解する上で重要な発見です。これらの分子がどのように生命現象に関与しているのかをさらに研究することで、様々な疾患の病態解明や創薬研究に貢献できる可能性があります。例えば、tRNAのチャージ率を制御することで、細胞の代謝やタンパク質合成を調節し、がんや神経疾患の治療に繋がる可能性があります。また、D-アラニンの概日リズムへの影響を理解することで、睡眠障害や生活習慣病の予防や治療法の開発に役立つと考えられます。
これらの研究成果は、健康な生活を送るための新たな知見をもたらし、社会全体の健康増進に貢献する可能性を秘めています。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (26 results)

All 2025 2024 2023 2022 Other

All Journal Article (18 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 18 results,  Open Access: 18 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Book (1 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] d-Alanine, a Circadian Metabolite that Regulates Glucose Metabolism and Viral Infection2025

    • Author(s)
      Kimura Tomonori、Sakai Shinsuke、Isaka Yoshitaka
    • Journal Title

      ChemBioChem

      Volume: 26 Issue: 7

    • DOI

      10.1002/cbic.202500018

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of Fast Decliner of Diabetic Kidney Disease Using Chiral Amino Acid Profiling: A Pilot Study2025

    • Author(s)
      Hirakawa Yosuke、Kimura Tomonori、Sakai Shinsuke、Mizui Masayuki、Mita Masashi、Isaka Yoshitaka、Nangaku Masaomi、Inagi Reiko
    • Journal Title

      Chemistry & Biodiversity

      Volume: NA Issue: 6

    • DOI

      10.1002/cbdv.202403332

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kinetic analysis of D-Alanine upon oral intake in humans2024

    • Author(s)
      Kimura Tomonori、Sakai Shinsuke、Horio Masaru、Takahara Shiro、Ishigo Shoto、Nakane Maiko、Negishi Eiichi、Imoto Hiroshi、Mita Masashi、Hamase Kenji、Higa-Maekawa Yoko、Kakuta Yoichi、Mizui Masayuki、Isaka Yoshitaka
    • Journal Title

      Amino Acids

      Volume: 56 Issue: 1 Pages: 61-61

    • DOI

      10.1007/s00726-024-03421-6

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum D-asparagine concentration adjusted for eGFR could serve as a novel screening tool for urothelial carcinoma2024

    • Author(s)
      Yamamoto Akinaru,Kawashima Atsunari,Sakai Shinsuke,Mita Masashi,Sassi Nesrine,Inoguchi Shunsuke,Horibe Yuki,Yoshimura Akihiro,Tani Masaru,Yutong Liu,Okuda Yohei,Oka Toshiki,Uemura Toshihiro,Yamamichi Gaku,Ishizuya Yu,Hayashi Takuji,Yamamoto Yoshiyuki, Imamura Ryoichi,Kimura Tomonori,Nonomura Norio etc.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 733 Pages: 150701-150701

    • DOI

      10.1016/j.bbrc.2024.150701

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Plasma d-asparagine and the d/l-serine ratio reflect chronic kidney diseases in children regardless of physique2024

    • Author(s)
      Morishita Toshimasa、Nishizaki Naoto、Taniguchi Sakiko、Sakai Shinsuke、Kimura Tomonori、Mita Masashi、Nakagawa Mayu、Endo Amane、Ohtomo Yoshiyuki、Yasui Masato、Shimizu Toshiaki、Sasabe Jumpei
    • Journal Title

      Amino Acids

      Volume: 56 Issue: 1 Pages: 38-38

    • DOI

      10.1007/s00726-024-03400-x

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Viral entry and translation in brain endothelia provoke influenza-associated encephalopathy2024

    • Author(s)
      Kimura-Ohba Shihoko、Kitamura Mieko、Tsukamoto Yusuke、Kogaki Shigetoyo、Sakai Shinsuke、Fushimi Hiroaki、Matsuoka Keiko、Takeuchi Makoto、Itoh Kyoko、Ueda Keiji、Kimura Tomonori
    • Journal Title

      Acta Neuropathologica

      Volume: 147 Issue: 1 Pages: 77-77

    • DOI

      10.1007/s00401-024-02723-z

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of individual variation of D-amino acids in human plasma by a two-dimensional LC-MS/MS system and application to the early diagnosis of chronic kidney disease2024

    • Author(s)
      Chiharu ISHII, Takeyuki AKITA, Tomonori KIMURA, Shinsuke SAKAI, Masashi MITA, Tomomi IDE, Yoshitaka ISAKA, Kenji HAMASE
    • Journal Title

      Analytical Chemistry

      Volume: 96 Issue: 12 Pages: 4876-4883

    • DOI

      10.1021/acs.analchem.3c05309

    • Related Report
      2024 Annual Research Report 2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of a three-dimensional HPLC system for the determination of serine, threonine and allo-threonine enantiomers in the plasma of patients with chronic kidney disease2024

    • Author(s)
      Mai OYAIDE, Chiharu ISHII, Takeyuki AKITA, Tomonori KIMURA, Shinsuke SAKAI, Masayuki MIZUI, Masashi MITA, Tomomi IDE, Yoshitaka ISAKA, Kenji HAMASE
    • Journal Title

      Journal of Chromatography A

      Volume: 1719 Pages: 464739-464739

    • DOI

      10.1016/j.chroma.2024.464739

    • Related Report
      2024 Annual Research Report 2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A multi-hierarchical approach reveals d-serine as a hidden substrate of sodium-coupled monocarboxylate transporters2024

    • Author(s)
      Wiriyasermkul Pattama、Moriyama Satomi、Suzuki Masataka、Kongpracha Pornparn、Nakamae Nodoka、Takeshita Saki、Tanaka Yoko、Matsuda Akina、Miyasaka Masaki、Hamase Kenji、Kimura Tomonori、Mita Masashi、Sasabe Jumpei、Nagamori Shushi
    • Journal Title

      eLife

      Volume: 12

    • DOI

      10.7554/elife.92615

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] d-Alanine Affects the Circadian Clock to Regulate Glucose Metabolism in the Kidney2023

    • Author(s)
      Sakai Shinsuke、Tanaka Youichi、Tsukamoto Yusuke、Kimura-Ohba Shihoko、Hesaka Atsushi、Hamase Kenji、Hsieh Chin-Ling、Kawakami Eiryo、Ono Hiraku、Yokote Kotaro、Yoshino Mitsuaki、Okuzaki Daisuke、Matsumura Hiroyo、Fukushima Atsuko、Mita Masashi、Nakane Maiko、Doi Masao、Isaka Yoshitaka、Kimura Tomonori
    • Journal Title

      Kidney360

      Volume: 5 Issue: 2 Pages: 237-251

    • DOI

      10.34067/kid.0000000000000345

    • Related Report
      2024 Annual Research Report 2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GCN2-kinase‐mediated upregulation of ubiquitin C maintains intracellular glutamine level and tRNA Gln(CUG) charging under amino acid starvation2023

    • Author(s)
      Tsukamoto Yusuke、Nakamura Yumi、Hirata Makoto、Okuzaki Daisuke、Sakate Ryuichi、Kimura Tomonori
    • Journal Title

      FEBS Letters

      Volume: 597 Issue: 12 Pages: 1638-1650

    • DOI

      10.1002/1873-3468.14628

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] D-Asparagine is an Ideal Endogenous Molecule for Measuring the Glomerular Filtration Rate2023

    • Author(s)
      Taniguchi Ayumu、Kawamura Masataka、Sakai Shinsuke、Kimura-Ohba Shihoko、Tanaka Yoko、Fukae Shota、Tanaka Ryo、Nakazawa Shigeaki、Yamanaka Kazuaki、Horio Masaru、Takahara Shiro、Nonomura Norio、Isaka Yoshitaka、Imamura Ryoichi、Kimura Tomonori
    • Journal Title

      Kidney International Reports

      Volume: 8 Issue: 6 Pages: 1192-1200

    • DOI

      10.1016/j.ekir.2023.03.009

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel in silico scaffold-hopping method for drug repositioning in rare and intractable diseases2023

    • Author(s)
      Tanabe Mao、Sakate Ryuichi、Nakabayashi Jun、Tsumura Kyosuke、Ohira Shino、Iwato Kaoru、Kimura Tomonori
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1

    • DOI

      10.1038/s41598-023-46648-1

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] d-Serine as a sensor and effector of the kidney2023

    • Author(s)
      Kimura Tomonori、Sakai Shinsuke、Isaka Yoshitaka
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 27 Issue: 11 Pages: 891-900

    • DOI

      10.1007/s10157-023-02384-4

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] d-Alanine as a biomarker and a therapeutic option for severe influenza virus infection and COVID-192023

    • Author(s)
      Kimura-Ohba Shihoko、Asaka Masamitsu N.、Utsumi Daichi、Takabatake Yoshitsugu、Takahashi Atsushi、Yasutomi Yasuhiro、Isaka Yoshitaka、Kimura Tomonori
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

      Volume: 1869 Issue: 1 Pages: 166584-166584

    • DOI

      10.1016/j.bbadis.2022.166584

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blood levels of d-amino acids reflect the clinical course of COVID-192023

    • Author(s)
      Kimura-Ohba Shihoko、Takabatake Yoshitsugu、Takahashi Atsushi、Tanaka Yoko、Sakai Shinsuke、Isaka Yoshitaka、Kimura Tomonori
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 34 Pages: 101452-101452

    • DOI

      10.1016/j.bbrep.2023.101452

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Profiling of kidney involvement in systemic lupus erythematosus by deep learning using the National Database of Designated Incurable Diseases of Japan2023

    • Author(s)
      Kimura Tomonori、Ikeuchi Hidekazu、Yoshino Mitsuaki、Sakate Ryuichi、Maruyama Shoichi、Narita Ichiei、Hiromura Keiju
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 27 Issue: 6 Pages: 519-527

    • DOI

      10.1007/s10157-023-02337-x

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] i-tRAP (individual tRNA acylation PCR): a convenient method for selective quantification of tRNA charging2022

    • Author(s)
      Yusuke Tsukamoto, Yumi Nakamura, Makoto Hirata, Ryuichi Sakate, Tomonori Kimura
    • Journal Title

      RNA

      Volume: - Issue: 1 Pages: 111-122

    • DOI

      10.1261/rna.079323.122

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Effects and dynamics of D-alanine under diabetic conditions2024

    • Author(s)
      Kimura T, Sakai S, Mita M, Mizui M, Isaka Y
    • Organizer
      アメリカ腎臓学会
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of kidney and viral diseases using D-amino acids2024

    • Author(s)
      Kimura T
    • Organizer
      国際D-アミノ酸研究会
    • Related Report
      2024 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 難治性腎疾患におけるリバーストランスレーショナル研究のupdateと今後の展望について2023

    • Author(s)
      木村友則
    • Organizer
      第46回 IgA腎症研究会学術集会
    • Related Report
      2023 Research-status Report
    • Invited
  • [Presentation] 難治性腎疾患に対する今後の展開について2023

    • Author(s)
      木村友則
    • Organizer
      第66回 日本腎臓学会学術総会 イブニングセミナー1
    • Related Report
      2023 Research-status Report
    • Invited
  • [Book] 腎臓から広がったD-アミノ酸の疾患横断的研究の展開2024

    • Author(s)
      木村友則
    • Total Pages
      5
    • Publisher
      東京 : 北隆館
    • Related Report
      2024 Annual Research Report
  • [Remarks] 正体不明だったアミノ酸に驚きの新発見! “体内時計”を整えて体調を良くするD-アミノ酸

    • URL

      https://resou.osaka-u.ac.jp/ja/research/2024/20240124_1

    • Related Report
      2024 Annual Research Report
  • [Remarks] トランスファーRNAの新たな評価方法の開発。難病や老化の病態解明研究での活用に期待。

    • URL

      https://www.nibiohn.go.jp/KAGAMI/news/2022/rnarnatrna.html

    • Related Report
      2022 Research-status Report
  • [Patent(Industrial Property Rights)] 生物学的および生理学的プロセスを感知するRNAの測定方法2022

    • Inventor(s)
      木村友則、塚本悠介
    • Industrial Property Rights Holder
      木村友則、塚本悠介
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2023 Research-status Report

URL: 

Published: 2022-07-05   Modified: 2026-01-16  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi