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Study of aging metabolites for remodeling of super-aging society

Research Project

Project/Area Number 20K20658
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Studies on the Super-Aging Society
Research InstitutionKyoto University

Principal Investigator

Kondoh Hiroshi  京都大学, 医学研究科, 准教授 (80402890)

Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Keywordsメタボローム / メタボライト / バイオマーカー / フレイル / サルコペニア / 老化 / 認知症
Outline of Research at the Start

「老化の多様性・恒常性」の理解の鍵として、我々は「メタボライトの個人差(多様性)」を見出し、新規老化マーカーや、飢餓マーカー発見の実績・ノウハウを積んできた。これら老化関連メタボライトをさらに他の加齢性疾患(フレイル、サルコペニア、骨粗鬆症)で検証すると同時に、その臨床介入応用を目指す。

Outline of Final Research Achievements

Metabolomics is one of newly-developed methods for detecting and analyzing small molecule metabolites by LC-MS and other methods, which is useful for elucidating the pathophysiology of diseases and searching for diagnostic biomarkers. Using our proprietary whole-blood metabolome technology, we searched for age-related disease biomarkers. 15 frailty markers and 22 sarcopenia markers were identified. The former includes mainly a decline in the antioxidants, while the latter comprises a decrease in the mitochondrial and muscular metabolites. Among the latter, 20 metabolites were ones elevated with renal impairment. Although the similarity of the clinical features between frailty and sarcopenia were noticed, distinct, non-overlapping profiles for metabolite markers for these two diseases were disclosed. Thirty-three dementia markers, classified into 5 subgroups, were also identified in our study.

Academic Significance and Societal Importance of the Research Achievements

「老化の多様性」に直面しつつある本邦では、寝たきりの手前の状態であるフレイルや、サルコペニア、認知症も増加している。本研究でのメタボロームからの加齢性疾患の検証は、新たな病態理解に有効であった。さらにこれを基盤として、将来、予後予測、診断マーカー、予防・治療モダリティへの応用が期待される。ひいては、高齢社会の再構築及び健康増進による国民および世界の幸福に寄与する。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (46 results)

All 2022 2021 2020 Other

All Journal Article (22 results) (of which Int'l Joint Research: 12 results,  Peer Reviewed: 22 results,  Open Access: 19 results) Presentation (19 results) (of which Int'l Joint Research: 2 results,  Invited: 12 results) Book (2 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Cellular Senescence in Diabetes Mellitus: Distinct Senotherapeutic Strategies for Adipose Tissue and Pancreatic β Cells.2022

    • Author(s)
      Takaaki Murakami, Nobuya Inagaki, Hiroshi Kondoh.
    • Journal Title

      Frontiers in Endocrinology

      Volume: 13 Pages: 869414-869414

    • DOI

      10.3389/fendo.2022.869414

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] RNA-binding proteins: underestimated contributors in tumorigenesis.2022

    • Author(s)
      Zhao Y, Mir C, Garcia-Mayea Y, Paciucci R, Kondoh H, and LLeonart ME
    • Journal Title

      Seminars in Cancer Biology

      Volume: S1044 Pages: 20-7

    • DOI

      10.1016/j.semcancer.2022.01.010

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Targeting p21 for diabetes: Another choice of senotherapy.2022

    • Author(s)
      Hiroshi Kondoh and Eiji Hara.
    • Journal Title

      Cell metabolism

      Volume: 34 Issue: 1 Pages: 5-7

    • DOI

      10.1016/j.cmet.2021.12.008

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reply to Zheng et al.: Clinical metabolomics: Detailed analysis by nontargeted method is complementary to large-scale studies.2022

    • Author(s)
      Hiroshi Kondoh, Takayuki Teruya, Yung-Ju Chen, Yasuhide Fukuji, Mitsuhiro Yanagida.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 119 Issue: 5

    • DOI

      10.1073/pnas.2120693119

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Decline of ergothioneine in frailty and cognition impairment2022

    • Author(s)
      Kondoh Hiroshi、Teruya Takayuki、Kameda Masahiro、Yanagida Mitsuhiro
    • Journal Title

      FEBS Letters

      Volume: 596 Issue: 10 Pages: 1270-1278

    • DOI

      10.1002/1873-3468.14299

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Metabolic shift to serine biosynthesis through 3-PG accumulation and PHGDH induction promotes tumor growth in pancreatic cancer2021

    • Author(s)
      Itoyama R, Yasuda-Yoshihara N, Kitamura F, Yasuda T, Bu L, Yonemura A, Uchihara T, Arima K, Hu X, Jun Z, Okamoto Y, Akiyama T, Yamashita K, Nakao Y, Yusa T, Kitano Y, Higashi T, Miyata T, Imai K, Hayashi H, Yamashita Y, Mikawa T, Kondoh H, Baba H, Ishimoto T
    • Journal Title

      Cancer Letters

      Volume: 523 Pages: 29-42

    • DOI

      10.1016/j.canlet.2021.09.007

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reduced uremic metabolites are prominent feature of sarcopenia, distinct from antioxidative markers for frailty2021

    • Author(s)
      Kameda Masahiro、Teruya Takayuki、Yanagida Mitsuhiro、Kondoh Hiroshi
    • Journal Title

      Aging

      Volume: 13 Issue: 17 Pages: 20915-20934

    • DOI

      10.18632/aging.203498

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Whole blood metabolomics of dementia patients reveal classes of disease linked metabolites.2021

    • Author(s)
      Takayuki Teruya, Yung-Ju Chen, Hiroshi Kondoh, Yasuhide Fukuji, Mitsuhiro Yanagida.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 118 Issue: 37

    • DOI

      10.1073/pnas.2022857118

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterization of genetically modified mice for phosphoglycerate mutase, a vitally-essential enzyme in glycolysis2021

    • Author(s)
      Mikawa T, Shibata E, Shimada M, Ito K, Ito T, Kanda H, Takubo K, Shimada A, Lleonart ME, Inagaki N, Yokode M, Kondoh H
    • Journal Title

      PLoS One

      Volume: 16 Issue: 4 Pages: e0250856-e0250856

    • DOI

      10.1371/journal.pone.0250856

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 「フレイルのバイオマーカー研究の展望」2021

    • Author(s)
      亀田雅博、近藤祥司
    • Journal Title

      日本老年医学会雑誌

      Volume: 58

    • NAID

      130008084942

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 「老化制御機構の新展開;慢性炎症除去やセノリシス」2021

    • Author(s)
      近藤祥司
    • Journal Title

      医歯薬出版・週刊『医学のあゆみ』

      Volume: 279

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 「フレイルの進行状態を反映する血液メタボライト」2021

    • Author(s)
      亀田雅博、近藤祥司
    • Journal Title

      「バイオサイエンスとインダストリーB&I」誌

      Volume: 79 Pages: 28-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reply to Pan et al.: Whole blood metabolome analysis combined with comprehensive frailty assessment.2021

    • Author(s)
      Masahiro Kameda, Takayuki Teruya, Mitsuhiro Yanagida, and Hiroshi Kondoh.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 118 Issue: 1

    • DOI

      10.1073/pnas.2016640118

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Whole Blood Metabolomics in Aging Research.2021

    • Author(s)
      Hiroshi Kondoh, Masahiro Kameda, and Mitsuhiro Yanagida.
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 22 Issue: 1 Pages: 175-175

    • DOI

      10.3390/ijms22010175

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficient and rapid assessment of multiple aspects of frailty using the Kyoto Frailty Scale, developed from the Edmonton Frail Scale2021

    • Author(s)
      Masahiro Kameda, Rie Shibata, and Hiroshi Kondoh.
    • Journal Title

      Journal of Physical Therapy Science

      Volume: 33 Issue: 3 Pages: 267-273

    • DOI

      10.1589/jpts.33.267

    • NAID

      130007999457

    • ISSN
      0915-5287, 2187-5626
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Editorial: How do metabolism, angiogenesis, and hypoxia modulate resistance?2021

    • Author(s)
      Hiroshi Kondoh, Josep Castellvi, Matilde E. LLeonart.
    • Journal Title

      Frontiers in Oncology

      Volume: 10 Pages: 1-1

    • DOI

      10.3389/fonc.2021.671222

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Frailty markers comprise blood metabolites involved in antioxidation, cognition, and mobility.2020

    • Author(s)
      Masahiro Kameda, Takayuki Teruya, Mitsuhiro Yanagida, and Hiroshi Kondoh.
    • Journal Title

      PNAS

      Volume: 117 Issue: 17 Pages: 9483-9489

    • DOI

      10.1073/pnas.1920795117

    • NAID

      120006826748

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phosphoglycerate Mutase Cooperates with Chk1 Kinase to Regulate Glycolysis2020

    • Author(s)
      Mikawa Takumi、Shibata Eri、Shimada Midori、Ito Ken、Ito Tomiko、Kanda Hiroaki、Takubo Keiyo、Lleonart Matilde E.、Inagaki Nobuya、Yokode Masayuki、Kondoh Hiroshi
    • Journal Title

      iScience

      Volume: 23 Issue: 7 Pages: 101306-101306

    • DOI

      10.1016/j.isci.2020.101306

    • NAID

      120006870881

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] T cell-specific deletion of Pgam1 reveals a critical role for glycolysis in T cell responses.2020

    • Author(s)
      Toriyama K, Kuwahara M, Kondoh H, Mikawa T, Takemori N, Konishi A., Yorozuya T, Yamada T, Soga T., Shiraishi A, and Yamashita M.
    • Journal Title

      Communications Biology

      Volume: 3 Issue: 1 Pages: 1-13

    • DOI

      10.1038/s42003-020-01122-w

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metabolomics of human fasting: New insights about old questions.2020

    • Author(s)
      Hiroshi Kondoh, Takayuki Teruya, and Mitsuhiro Yanagida.
    • Journal Title

      Open Biology

      Volume: 10 Issue: 9 Pages: 200176-200176

    • DOI

      10.1098/rsob.200176

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autophagy Takes Center Stage as a Possible Cancer Hallmark.2020

    • Author(s)
      Jose Alvarez-Meythaler, Yoelsis Garcia-Mayea, Cristina Mir, Hiroshi Kondoh, Matilde E. LLeonart
    • Journal Title

      Frontiers in Oncology

      Volume: 10 Pages: 1-23

    • DOI

      10.3389/fonc.2020.586069

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Senescence research from historical theory to future clinical application.2020

    • Author(s)
      M Kameda, T Mikawa, M Yokode, N Inagaki, H Kondoh.
    • Journal Title

      Geriatr. Gerontol. Int

      Volume: 21 Issue: 2 Pages: 125-130

    • DOI

      10.1111/ggi.14121

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Whole blood metabolome for frailty and sarcopenia2022

    • Author(s)
      近藤祥司
    • Organizer
      10th international Singapore Lipid Symposium (iSLS10)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] サルコペニア・フレイルの血液メタボローム2022

    • Author(s)
      近藤祥司
    • Organizer
      老化と代謝セミナー
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] フレイル診療で繋ぐ地域連携2022

    • Author(s)
      近藤祥司
    • Organizer
      高齢者医療の地域連携を考える会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 地域で高齢者のフレイル予防をすすめる2022

    • Author(s)
      近藤祥司
    • Organizer
      左京南日常生活圏域(5学区合同)地域ケア会議
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 老化関連メタボライトや解糖系代謝機構の探索2021

    • Author(s)
      近藤祥司
    • Organizer
      日本動脈硬化学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] フレイルと血液メタボローム2021

    • Author(s)
      近藤祥司
    • Organizer
      抗加齢医学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Identification of the metabolites and glycolytic regulation involved in ageing and its relevant diseases2021

    • Author(s)
      近藤祥司
    • Organizer
      RENKEI Researcher Online Workshop Exploring Japan-UK Research Collaborations in Health
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 老化・加齢性疾患に関連するメタボライトや解糖系代謝機構の解明2021

    • Author(s)
      近藤祥司
    • Organizer
      老年医学会・基礎老化学会合同シンポ
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 簡易版京都フレイルスケールKFSの開発2021

    • Author(s)
      亀田雅博、近藤祥司
    • Organizer
      日本老年医学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 全血を含む血液網羅的メタボロミクスによる、老化に関連するメタボローム研究:老化、絶食からフレイル研究に至る知見より2021

    • Author(s)
      亀田雅博、 近藤祥司
    • Organizer
      日本老年医学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 老化・加齢性疾患に関連するメタボライトや解糖系代謝機構の解明2021

    • Author(s)
      近藤祥司
    • Organizer
      先端モデル動物支援プラットフォーム成果発表会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 網羅的全血メタボロームによる老化研究2020

    • Author(s)
      近藤祥司
    • Organizer
      第43回日本基礎老化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 網羅的全血メタボローム解析による新規フレイルマーカーの発見2020

    • Author(s)
      近藤祥司
    • Organizer
      日本老年医学会
    • Related Report
      2020 Research-status Report
  • [Presentation] PGAM の「非酵素機能」によるワールブルグ解糖系新規制御機構2020

    • Author(s)
      近藤祥司
    • Organizer
      日本抗加齢医学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 解糖系酵素PGAMモデルマウスの解析2020

    • Author(s)
      近藤祥司
    • Organizer
      日本抗加齢医学会
    • Related Report
      2020 Research-status Report
  • [Presentation] ヒト血液メタボローム解析による老化研究2020

    • Author(s)
      近藤祥司
    • Organizer
      日本抗加齢医学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 簡易版京都フレイルスクリーニングスケール「KFS」の有用性2020

    • Author(s)
      近藤祥司
    • Organizer
      日本老年医学会近畿地方会
    • Related Report
      2020 Research-status Report
  • [Presentation] 網羅的全血メタボローム解析による新規フレイルマーカーの発見2020

    • Author(s)
      近藤祥司
    • Organizer
      日本老年医学会近畿地方会
    • Related Report
      2020 Research-status Report
  • [Presentation] 老化や加齢性疾患関連メタボライトと解糖系代謝機構の同定2020

    • Author(s)
      近藤祥司
    • Organizer
      日本分子生物学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Book] 「遺伝学の百科事典;継承と多様性の源」2022

    • Author(s)
      近藤祥司
    • Total Pages
      690
    • Publisher
      日本遺伝学会編 丸善出版
    • Related Report
      2021 Annual Research Report
  • [Book] 「内科学(第12版)」2022

    • Author(s)
      近藤祥司
    • Total Pages
      2640
    • Publisher
      朝倉書店
    • Related Report
      2021 Annual Research Report
  • [Remarks] 老化の多様性・恒常性を規定する解糖系代謝・メタボライトの探索

    • URL

      http://www.anti-aging.jpn.com/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 近藤祥司 老化と代謝研究室

    • URL

      http://www.anti-aging.jpn.com/

    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] Blood metabolic markers for frail elderly patients2020

    • Inventor(s)
      柳田充弘、近藤祥司、亀田雅博、照屋貴之
    • Industrial Property Rights Holder
      柳田充弘、近藤祥司、亀田雅博、照屋貴之
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-182716
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report

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Published: 2020-08-03   Modified: 2024-12-25  

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