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Establishment of blood-based biomarkers to reflect age-related changes in biological membrane

Research Project

Project/Area Number 22K19762
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 InstitutionOkayama University of Science

Principal Investigator

Kimura Nobuyuki  岡山理科大学, 獣医学部, 教授 (80392330)

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 / バイオマーカー / 細胞外微小胞 / 高等霊長類モデル / 生体膜
Outline of Research at the Start

超高齢化社会に突入した我が国ではサルコペニアに代表されるフレイルへの対策が急務となっているが、老化の進行度は個人差が大きいため、各個人の老化レベルを客観的に評価できるバイオマーカーの確立が求められている。
近年、炎症と老化との関係が大きく注目されているが、炎症は癌や感染症の他、肥満との関係も指摘されており、必ずしも純粋に老化と相関するとは言えない。
本研究はこれまで申請者が積み重ねてきた研究成果をもとに、生体膜の質的変化から各個人の老化を客観的に評価できるバイオマーカーの開発を目的としており、生体膜のオミックス解析=メンブレノミクスという新たな学術領域の開拓につながる挑戦的研究でもある

Outline of Final Research Achievements

In cynomolgus monkeys, the levels of extracellular vesicles (EVs) secreted in plasma increased with aging. Proteomic analysis of plasma-derived EVs showed a significant increase in Apolipoprotein A-I (ApoA-I) levels. Since the levels of ApoA-I in blood are considered to correlate with cognitive decline in humans, the levels of ApoA-I in plasma-derived EVs may be a new indicator of brain aging as well as lipid metabolism. On the other hand, a decrease in gonad-derived proteins such as Pregnancy zone protein was observed. This finding suggets that plasma-derived EVs could be used as a new evaluation system for reproductive functions associated with aging.

Translated with DeepL.com (free version)

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により、個体老化を簡便且つ客観的に評価できる血液由来バイオマーカーの開発が実現できる可能性が大きく高まった。また、膜の質的変化に着目したプロテオミクス解析によって加齢性変化を示す様々な膜蛋白質の同定に成功したことから、生体膜そのもののオミックス解析=メンブレノミクスという新たな生化学的解析手法の有効性が示された。さらに、本研究によって同定された血漿由来細胞外微小胞の膜蛋白質をターゲットとすることで、老化に伴う認知機能や生殖機能の低下を評価するための新たな検索性の開発も期待できる。

Report

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

    (5 results)

All 2024 2023 2022

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Dysregulation of stress granule dynamics by DCTN1 deficiency exacerbates TDP-43 pathology in Drosophila models of ALS/FTD.2024

    • Author(s)
      Ueda T, Takeuchi T, Fujikake N, Suzuki M, Minakawa EN, Ueyama M, Fujino Y, Kimura N, Nagano S, Yokoseki A, Onodera O, Mochizuki H, Mizuno T, Wada K, Nagai Y.
    • Journal Title

      Acta Neuropathol Commun

      Volume: 12 Issue: 1 Pages: 20-20

    • DOI

      10.1186/s40478-024-01729-8

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cynomolgus macaque model of neuronal ceroid lipofuscinosis type 2 disease2023

    • Author(s)
      Munesue Yoshiko、Ageyama Naohide、Kimura Nobuyuki、Takahashi Ichiro、Nakayama Shunya、Okabayashi Sachi、Katakai Yuko、Koie Hiroshi、Yagami Ken-ichi、Ishii Kazuhiro、Tamaoka Akira、Yasutomi Yasuhiro、Shimozawa Nobuhiro
    • Journal Title

      Experimental Neurology

      Volume: 363 Pages: 114381-114381

    • DOI

      10.1016/j.expneurol.2023.114381

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Age-related alterations in protein phosphatase 2A methylation levels in brains of cynomolgus monkeys: a pilot study2023

    • Author(s)
      Ando Sana、Sakurai Masashi、Shibutani Shusaku、Kimura Nobuyuki、Shimozawa Nobuhiro、Yasutomi Yasuhiro、Yabe Ryotaro、Ohama Takashi、Sato Koichi
    • Journal Title

      The Journal of Biochemistry

      Volume: - Issue: 6 Pages: 1093-1093

    • DOI

      10.1093/jb/mvad006

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Presentation] The relationship between endocytic disturbance and Alzheimer's disease: Findings from Zoobiquity2023

    • Author(s)
      Nobuyuki Kimura
    • Organizer
      IAGG Asia/Oceania Regional Congress 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] アルツハイマー病のZoobiquity研究:ヒトサロゲートモデルとしてのカニクイザル2022

    • Author(s)
      木村展之
    • Organizer
      第30回サル疾病ワークショップ
    • Related Report
      2022 Research-status Report
    • Invited

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

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