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Age-related memory impairment and glucose metabolism in the brain

Research Project

Project/Area Number 19K21593
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

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

Principal Investigator

Ando Kanae  東京都立大学, 理学研究科, 准教授 (40632500)

Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords老化 / 糖代謝 / 脳 / グルコーストランスポーター / ショウジョウバエ / カロリー制限 / 神経変性疾患 / 脳高次機能 / aging / brain / glucose / mitochondria / glycolysis / Drosophila / dietary restriction / memory / 学習・記憶
Outline of Research at the Start

目的1. これまでにグルコーストランスポーター (Glut) の過剰発現で加齢による神経細胞内ATP減少を抑制できることを見出した。LC-MS/MSによる網羅的メタボローム解析により、加齢に伴って低下しさらにGlutの過剰発現でその低下が抑制される代謝物を同定する。
目的2. パブロフ型匂い忌避条件付けによりGlutを脳神経細胞に過剰発現したショウジョウバエでの加齢による記憶力の変化を調べる。
目的3. 記憶能力の加齢に伴う変化を通常の餌で飼育した個体と低栄養餌で飼育した個体で、パブロフ型匂い忌避条件付けによる記憶形成を若齢・老齢で調べ、比較する。

Outline of Final Research Achievements

Brain neurons play a central role in organismal aging, but there is conflicting evidence about the roles of neuronal glucose availability, glucose uptake and metabolism in aging and extended lifespan. We analyzed metabolic changes in the brain neurons of Drosophila during aging. Using a genetically-encoded fluorescent ATP biosensor, we found decreased ATP concentration in the neuronal somata of aged flies. The age-associated reduction in ATP concentration did not occur in brain neurons with suppressed glycolysis or enhanced glucose uptake, suggesting these pathways contribute to reductions in ATP. Increasing glucose uptake maintained ATP levels, suppressed age-dependent locomotor deficits and extended the life span. Increasing neuronal glucose uptake during dietary restriction resulted in the longest lifespans, suggesting an additive effect of enhancing glucose availability during a bioenergetic challenge on aging.

Academic Significance and Societal Importance of the Research Achievements

本研究から、老化した神経細胞でATPが低下することが加齢に伴う身体機能低下に関わることが示唆された。神経細胞のみでグルコース取り込みを促進すると、神経細胞内ATPを維持し、身体機能低下を抑制することができた。また食餌制限との組み合わせにより、さらに寿命を延伸したことから、神経細胞の糖代謝促進は、摂取カロリーなどライフスタイルの改善と相乗的に抗老化効果を発揮する可能性がある。今後ヒトへの応用を考えたとき、神経細胞特異的にグルコース取り込みを促進する戦略の開発が課題となる。神経細胞に特異的なグルコーストランスポーターの制御機構を標的とするなど、その戦略を検討することで、抗脳老化創薬に結びつけたい。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (26 results)

All 2022 2021 2020 2019 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (14 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Remarks (7 results)

  • [Journal Article] 5‐Aminolevulinic acid and sodium ferrous citrate ameliorate muscle aging and extend healthspan in <i>Drosophila</i>2021

    • Author(s)
      Nozawa Naoko、Noguchi Marie、Shinno Kanako、Tajima Maki、Aizawa Shingo、Saito Taro、Asada Akiko、Ishii Takuya、Ishizuka Masahiro、Iijima Koichi M.、Ando Kanae
    • Journal Title

      FEBS Open Bio

      Volume: 12 Issue: 1 Pages: 295-305

    • DOI

      10.1002/2211-5463.13338

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Disulfide bond formation in microtubule-associated tau protein promotes tau accumulation and toxicity <i>in vivo</i>2021

    • Author(s)
      Saito Taro、Chiku Tomoki、Oka Mikiko、Wada-Kakuda Satoko、Nobuhara Mika、Oba Toshiya、Shinno Kanako、Abe Saori、Asada Akiko、Sumioka Akio、Takashima Akihiko、Miyasaka Tomohiro、Ando Kanae
    • Journal Title

      Human Molecular Genetics

      Volume: 30 Issue: 21 Pages: 1955-1967

    • DOI

      10.1093/hmg/ddab162

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increasing neuronal glucose uptake attenuates brain aging and promotes life span under dietary restriction in Drosophila2021

    • Author(s)
      Oka Mikiko、Suzuki Emiko、Asada Akiko、Saito Taro、Iijima Koichi M.、Ando Kanae
    • Journal Title

      iScience

      Volume: 24 Issue: 1 Pages: 101979-101979

    • DOI

      10.1016/j.isci.2020.101979

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microtubule affinity?regulating kinase 4 with an Alzheimer's disease-related mutation promotes tau accumulation and exacerbates neurodegeneration2020

    • Author(s)
      Oba Toshiya、Saito Taro、Asada Akiko、Shimizu Sawako、Iijima Koichi M.、Ando Kanae
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 50 Pages: 17138-17147

    • DOI

      10.1074/jbc.ra120.014420

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tau Abnormalities and Autophagic Defects in Neurodegenerative Disorders; A Feed-forward Cycle2020

    • Author(s)
      Samimi Nastaran、Asada Akiko、Ando Kanae
    • Journal Title

      Galen Medical Journal

      Volume: 9 Pages: 1681-1681

    • DOI

      10.31661/gmj.v9i0.1681

    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Enhancement of glucose uptake protects neurons against energetic stresses in aging and disease2022

    • Author(s)
      Mikiko Oka and Kanae Ando
    • Organizer
      The 99th Annual Meeting of the Physiological Society of Japan
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Increasing glucose uptake suppresses neurodegeneration in Alzheimer’s Disease model Drosophila2021

    • Author(s)
      Mikiko Oka, Koichi M. Iijima and Kanae Ando
    • Organizer
      The 44 th Annual Meeting of the Japan Neuroscience Society, Hyogo, Japan
    • Related Report
      2021 Annual Research Report
  • [Presentation] Neuronal glucose metabolism in brain aging and age-related neurodegenerative diseases2021

    • Author(s)
      Kanae Ando
    • Organizer
      The 64th Annual Meeting of the Japanese Society for Neurochemistry
    • Related Report
      2021 Annual Research Report
  • [Presentation] The effect of sugar intake on neurodegeneration in a Drosophila model of tau toxicity2021

    • Author(s)
      Chihiro Yamamoto and Kanae Ando
    • Organizer
      第40回日本認知症学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 神経細胞内ミトコンドリア局在異常は分解機能低下によるタンパク質の蓄積を引き起こす2021

    • Author(s)
      真野 叶子、鈴木 えみ子、三浦ゆり、飯島 浩一、安藤 香奈絵
    • Organizer
      第40回日本認知症学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ‘The Effects of Sugar Intake on Neurodegeneration in a Drosophila Model of Tau Toxicity2021

    • Author(s)
      Chihiro Yamamoto, Taro Saito, Akiko Asada, Kanae Ando.
    • Organizer
      Cell Bio Virtual 2021-An Online ASCB|EMBO Meeting
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経細胞でのミトコンドリア局在異常は翻訳異常とタンパク質蓄積を引き起こす2021

    • Author(s)
      真野 叶子、鈴木 えみ子、三浦ゆり、飯島 浩一、安藤 香奈絵
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 老化と加齢依存性疾患における脳神経細胞のグルコース代謝の役割2021

    • Author(s)
      安藤香奈絵
    • Organizer
      第63回歯科基礎医学会学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] “Enhancement of neuronal glucose uptake attenuates brain aging and promotes lifespan under dietary restriction.”2020

    • Author(s)
      Mikiko Oka, Emiko Suzuki, Koichi M. Iijima, Kanae Ando.
    • Organizer
      The 39th Annual Meeting of the Japan Society for Dementia Research, Online, Nov 27, 2020
    • Related Report
      2020 Research-status Report
  • [Presentation] 脳神経細胞の軸索ミトコンドリアの減少はタンパク質分解機能の低下とユビキチン化タンパク質の蓄積を引き起こす2020

    • Author(s)
      真野 叶子、鈴木 えみ子、飯島 浩一、 安藤 香奈絵
    • Organizer
      第63回日本神経化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Enhancement of neuronal glucose uptake protects against tau-induced neurodegeneration in a Drosophila model of Alzheimer’s disease2020

    • Author(s)
      Mikiko Oka, Koichi M. Iijima, Kanae Ando.
    • Organizer
      The 44th Annual Meeting of the Molecular Biology Society of Japan, Online, Dec 4, 2020
    • Related Report
      2020 Research-status Report
  • [Presentation] 脳老化とアルツハイマー病の予防・緩和を目指して:加齢による神経細胞のエネルギー欠乏の分子メカニズム(英)Fighting against brain aging and Alzheimer disease: Understanding and counteracting bioenergetic challenges in neurons」2020

    • Author(s)
      Kanae Ando
    • Organizer
      日本分子生物学会年会 (MBSJ2020 Online) 3PW-02ワークショップ「Facilitating the use of Drosophila in clinical and translational biomedical research
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] ‘Enhancement of glucose uptake to maintain ATP levels in the brain neurons and reducing circulating glucose levels synergistically antagonize the aging in Drosophila.’ NEURO2019:2019

    • Author(s)
      Mikiko Oka, Emiko Suzuki, Koichi M. Iijima, Kanae Ando.
    • Organizer
      the 42nd Annual Meeting of the Japan Neuroscience Society and the 62nd Annual Meeting of the Japanese Society for Neurochemistry, Niigata, Japan, July 26, 2019 (Oral presentation)
    • Related Report
      2019 Research-status Report
  • [Presentation] ‘Enhancement of glucose uptake and calorie restriction antagonize age-dependent reductions in brain ATP levels and synergistically extend lifespan in Drosophila’2019

    • Author(s)
      Mikiko Oka, Emiko Suzuki, Koichi M. Iijima, Kanae Ando.
    • Organizer
      Society for Neuroscience the 49th annual meeting, Chicago, USA, October 19, 2019 (Poster presentation)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] 【研究発表】東京都立大学による米国科学誌「FEBS Open Bio」への5-ALAに関する研究論文

    • URL

      https://www.tmu.ac.jp/news/topics/31483.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 【研究発表】タウ蓄積の新たなスイッチを発見! ~ジスルフィド結合の形成をブロックすることで、

    • URL

      https://www.tmu.ac.jp/extra/download.html?d=assets/files/download/auth/press/20210621_press.pdf

    • Related Report
      2021 Annual Research Report
  • [Remarks] EurekAlert! Science News

    • URL

      https://www.eurekalert.org/news-releases/782092

    • Related Report
      2021 Annual Research Report
  • [Remarks] Better diet and glucose uptake in the brain

    • URL

      https://www.eurekalert.org/pub_releases/2021-01/tmu-bda010821.php

    • Related Report
      2020 Research-status Report
  • [Remarks] 脳の老化と寿命に関わるメカニズムを発見 ―脳内の糖がぴんぴんころりの鍵

    • URL

      https://www.tmu.ac.jp/news/topics/30590.html

    • Related Report
      2020 Research-status Report
  • [Remarks] Cause of Alzheimer's disease traced to mutation

    • URL

      https://www.eurekalert.org/pub_releases/2020-10/tmu-coa102120.php

    • Related Report
      2020 Research-status Report
  • [Remarks] アルツハイマー病の発症に関わる神経細胞死のメカニズムを解明:治療薬の開発にもヒント

    • URL

      https://www.tmu.ac.jp/news/topics/30417.html

    • Related Report
      2020 Research-status Report

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Published: 2019-07-04   Modified: 2023-01-30  

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