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Identification of senescent cells in the tissues of aged animals and the effect of their removal on prolonging individual life span.

Research Project

Project/Area Number 19H04043
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionTokyo Metropolitan Geriatric Hospital and Institute of Gerontology

Principal Investigator

Ishigami Akihito  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (50270658)

Co-Investigator(Kenkyū-buntansha) 橋本 真一  和歌山県立医科大学, 先端医学研究所, 教授 (00313099)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords老化 / 老化関連遺伝子 / 老化細胞 / トランスクリプトーム解析 / シングルセル遺伝子発現解析
Outline of Research at the Start

若齢動物の組織には、細胞機能に異常のない「若い細胞」のみが存在する。一方、老齢動物の組織には、細胞機能が衰退、異常化した「老化細胞」が存在し、その数も加齢に伴い増加することが予想される。本研究では、シングルセル(1細胞)遺伝子発現解析(Nx1-seq)により、老化に関連した遺伝子をシングルセルレベルで包括的に探索、同定する。

Outline of Final Research Achievements

To identify senescent cells in tissues and organs of aged animals, we attempted to identify age-associated genes (AGs) and senescent cells by single-cell transcriptome analysis. We found three age-associated genes (AG1, AG2, and AG3). According to previous reports, AG1 is involved in induction of apoptosis, AG2 inhibition of inflammation, and AG3 inhibition of cell proliferation. However, there have been no reports showing a relationship between AG1, AG2, and AG3 and aging. Histological analysis revealed AG1-positive cells in the liver of aged animals, which are likely to be senescent cells. If we can identify senescent cells in aged animals, we can search for senolytic drugs that actively eliminate these cells and apply them to clinical use in humans.

Academic Significance and Societal Importance of the Research Achievements

本研究により得られる研究成果は,誰もが知りたい「老化機構の解明」,そして日本における高齢者の健康寿命の延伸(老化制御)に繋がる.

Report

(4 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (26 results)

All 2022 2021 2020 2019

All Journal Article (15 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 15 results,  Open Access: 13 results) Presentation (10 results) (of which Invited: 10 results) Book (1 results)

  • [Journal Article] Vitamin C Is Essential for the Maintenance of Skeletal Muscle Functions2022

    • Author(s)
      Takisawa Shoko、Takino Yuka、Lee Jaewon、Machida Shuichi、Ishigami Akihito
    • Journal Title

      Biology

      Volume: 11 Issue: 7 Pages: 955-955

    • DOI

      10.3390/biology11070955

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Influence of oestrogen on satellite cells and myonuclear domain size in skeletal muscles following resistance exercise2022

    • Author(s)
      Hung Yung‐Li、Sato Ayami、Takino Yuka、Ishigami Akihito、Machida Shuichi
    • Journal Title

      Journal of Cachexia, Sarcopenia and Muscle

      Volume: 13 Issue: 5 Pages: 2525-2536

    • DOI

      10.1002/jcsm.13031

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Compartmentalized citrullination in Muller glial endfeet during retinal degeneration2022

    • Author(s)
      Palko Sarah I.、Saba Nicholas J.、Mullane Elias、Nicholas Benjamin D.、Nagasaka Yosuke、Ambati Jayakrishna、Gelfand Bradley D.、Ishigami Akihito、Bargagna-Mohan Paola、Mohan Royce
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 9

    • DOI

      10.1073/pnas.2121875119

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Determination of tissue-specific interaction between vitamin C and vitamin E <i>in vivo</i> using senescence marker protein-30 knockout mice as a vitamin C synthesis deficiency model2021

    • Author(s)
      Sato Ayami、Takino Yuka、Yano Tomohiro、Fukui Koji、Ishigami Akihito
    • Journal Title

      British Journal of Nutrition

      Volume: - Issue: 6 Pages: 1-11

    • DOI

      10.1017/s0007114521004384

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acerola (<i>Malpighia emarginata</i> DC.) Promotes Ascorbic Acid Uptake into Human Intestinal Caco-2 Cells via Enhancing the Gene Expression of Sodium-Dependent Vitamin C Transporter 12020

    • Author(s)
      TAKINO Yuka、AOKI Hitoshi、KONDO Yoshitaka、ISHIGAMI Akihito
    • Journal Title

      Journal of Nutritional Science and Vitaminology

      Volume: 66 Issue: 4 Pages: 296-299

    • DOI

      10.3177/jnsv.66.296

    • NAID

      130007893269

    • ISSN
      0301-4800, 1881-7742
    • Year and Date
      2020-08-31
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ascorbic acid during the suckling period is required for proper DNA demethylation in the liver2020

    • Author(s)
      Kawahori Kenichi、Kondo Yoshitaka、Yuan Xunmei、Kawasaki Yuki、Hanzawa Nozomi、Tsujimoto Kazutaka、Wada Fumiko、Kohda Takashi、Ishigami Akihito、Yamada Tetsuya、Ogawa Yoshihiro、Hashimoto Koshi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 21228-21228

    • DOI

      10.1038/s41598-020-77962-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Age-associated changes in the transcriptomes of non-cultured adipose-derived stem cells from young and old mice assessed via single-cell transcriptome analysis2020

    • Author(s)
      Doshida Yuta、Sano Haruka、Iwabuchi Sadahiro、Aigaki Toshiro、Yoshida Masayuki、Hashimoto Shinichi、Ishigami Akihito
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 11 Pages: e0242171-e0242171

    • DOI

      10.1371/journal.pone.0242171

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiation-induced gastrointestinal syndrome is exacerbated in vitamin C insufficient SMP30/GNL knockout mice2020

    • Author(s)
      Saga R, Uchida T, Takino Y, Kondo Y, Kobayashi H, Kinoshita M, Saitoh D, Ishigami A, Makishima M
    • Journal Title

      Nutrition

      Volume: 81 Pages: 1-8

    • DOI

      10.1016/j.nut.2020.110931

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Age-related dysfunction of p53-regulated phagocytic activity in macrophages2020

    • Author(s)
      Yamaguchi Yohko、Kaida Kohei、Suenaga Yusuke、Ishigami Akihito、Kobayashi Yoshiro、Nagata Kisaburo
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 529 Issue: 2 Pages: 462-466

    • DOI

      10.1016/j.bbrc.2020.05.121

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vimentin citrullination probed by a novel monoclonal antibody serves as a specific indicator for reactive astrocytes in neurodegeneration2020

    • Author(s)
      Jang B.、Kim M.J.、Lee Y.J.、Ishigami A.、Kim Y.S.、Choi E.K.
    • Journal Title

      Neuropathology and Applied Neurobiology

      Volume: 46 Issue: 7 Pages: 751-769

    • DOI

      10.1111/nan.12620

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Decreased ADAM17 expression in the lungs of α-Klotho reduced mouse.2020

    • Author(s)
      Keiko Akasaka-Manya, Hiroshi Manya, Satomi Nadanaka, Hiroshi Kitagawa , Yoshitaka Kondo, Akihito Ishigami and Tamao Endo
    • Journal Title

      J. Biochem.

      Volume: - Issue: 5 Pages: 483-493

    • DOI

      10.1093/jb/mvz113

    • NAID

      40022226796

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-Dose Vitamin C Preadministration Reduces Vancomycin-Associated Nephrotoxicity in Mice2019

    • Author(s)
      TAKIGAWA Masaki、YATSU Tomofumi、TAKINO Yuka、MATSUMOTO Shigekiyo、KITANO Takaaki、LEE Jaewon、ARAI Tomio、TANAKA Hiroyuki、ISHII Toshihiro、MORI Yoshiko、ISHIGAMI Akihito
    • Journal Title

      Journal of Nutritional Science and Vitaminology

      Volume: 65 Issue: 5 Pages: 399-404

    • DOI

      10.3177/jnsv.65.399

    • NAID

      130007738899

    • ISSN
      0301-4800, 1881-7742
    • Year and Date
      2019-10-31
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Age-dependent changes in vancomycin-induced nephrotoxicity in mice2019

    • Author(s)
      Takigawa Masaki、Masutomi Hirofumi、Shimazaki Yoshitomo、Arai Tomio、Lee Jaewon、Ishii Toshihiro、Mori Yoshiko、Ishigami Akihito
    • Journal Title

      Journal of Toxicologic Pathology

      Volume: 32 Issue: 1 Pages: 57-66

    • DOI

      10.1293/tox.2018-0036

    • NAID

      130007575089

    • ISSN
      0914-9198, 1881-915X
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vitamin C and vitamin E double-deficiency increased neuroinflammation and impaired conditioned fear memory2019

    • Author(s)
      Takahashi Keita、Yanai Shuichi、Takisawa Shoko、Kono Nozomu、Arai Hiroyuki、Nishida Yoichiro、Yokota Takanori、Endo Shogo、Ishigami Akihito
    • Journal Title

      Archives of Biochemistry and Biophysics

      Volume: 663 Pages: 120

    • DOI

      10.1016/j.abb.2019.01.003

    • URL

      https://pure.teikyo.jp/en/publications/e6bf0303-b045-48fc-86ff-f8796ae664e5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vitamin C deficiency causes muscle atrophy and a deterioration in physical performance.2019

    • Author(s)
      Takizawa, S., Funakoshi, T., Yatsu, T., Nagata, K., Aigaki, T., Machida, S., and Ishigami. A
    • Journal Title

      Sci. Rep.

      Volume: 9 Issue: 1 Pages: 4702-4702

    • DOI

      10.1038/s41598-019-41229-7

    • NAID

      130007919173

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ビタミンCの新しい健康機能-新型コロナウイルスに対するCの効果を考える-2020

    • Author(s)
      石神昭人
    • Organizer
      第59回日本栄養・食糧学会近畿支部大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 誰もが望む健康長寿の達成に欠かせないビタミンC2020

    • Author(s)
      石神昭人
    • Organizer
      2020年度ライフイノベーション研究所シンポジウム, 東洋大学ライフイノベーション研究所(Web開催)
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 皮膚におけるビタミンCの働き-皮膚でのエピジェネティクス研究も含めて-2020

    • Author(s)
      石神昭人
    • Organizer
      第38回日本美容皮膚科学会総会・学術大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] グルコノラクトナーゼ遺伝子破壊マウスを用いたビタミンCに関する諸問題へのアプローチ2020

    • Author(s)
      石神昭人
    • Organizer
      日本ビタミン学会第72回大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 漢方薬の抗酸化作用~ビタミンCの話題も交えて~2019

    • Author(s)
      石神昭人
    • Organizer
      日本東洋医学会茨城地方部会 第26回茨城県部会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] タミンCの長期的な不足は寿命を短縮する2019

    • Author(s)
      石神昭人
    • Organizer
      第66回 日本栄養改善学会学術総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ビタミンC合成不全マウスを用いた老化研究 -健康長寿を目指して-2019

    • Author(s)
      石神昭人
    • Organizer
      第1回 ビタミンC研究委員会シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 健康寿命と食生活:健康寿命を延ばすためのビタミンC研究、基礎から臨床まで2019

    • Author(s)
      石神昭人
    • Organizer
      第46回東京成長ホルモン成長因子セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ビタミンCによる老化制御の可能性2019

    • Author(s)
      石神昭人
    • Organizer
      第31回日本老年学会総会(合同大会)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 老化研究における老年医学研究者からみた、技術者の貢献2019

    • Author(s)
      石神昭人
    • Organizer
      平成30年度日本実験動物技術者協会関東支部総会 第44回懇話会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Book] 寿命と成長『動物の事典』2020

    • Author(s)
      石神昭人
    • Total Pages
      746
    • Publisher
      朝倉書店
    • Related Report
      2020 Annual Research Report

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Published: 2019-04-18   Modified: 2024-01-30  

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