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Identification of aestivation-dependent longevity and its regulation

Research Project

Project/Area Number 20K20664
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

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

Principal Investigator

Nishiyama Akira  香川大学, 医学部, 教授 (10325334)

Co-Investigator(Kenkyū-buntansha) 杉浦 悠毅  慶應義塾大学, 医学部(信濃町), 特任講師 (30590202)
鈴木 美和  日本大学, 生物資源科学部, 教授 (70409069)
植田 啓一  一般財団法人沖縄美ら島財団(総合研究センター), 総合研究センター 動物研究室, 上席研究員 (70721728)
大崎 博之  神戸大学, 保健学研究科, 准教授 (80438291)
Project Period (FY) 2020-07-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords夏眠 / 夏眠様反応 / 生体防御反応 / 体液 / 老化 / 健康長寿 / 生活習慣病 / 個体老化 / 腎臓病 / 血圧 / サルコペニア / 体液変化 / イルカ / 宇宙空間
Outline of Research at the Start

健康長寿を目指したこれまでの研究は、個体の「機能低下を生じる要因」に着目し、その要因を阻害あるいは補填して解決を図ろうとするものばかりであり、根本的な解決には至っていない。

そこで視点を180度変え、最近申請者が世界に先駆けて発見した陸上高等動物が持つ目に見えない個体の適応能力である「夏眠(aestivation)反応」に着目し、それを制御することで老化防止や生活習慣病の未病に挑戦する。

先行研究で証明しているげっ歯類の「夏眠」モデルを使用した「夏眠反応」の制御メカニズムの解析や海生哺乳類・イルカでの検討により、新しい学術分野を切り開き、究極の健康長寿獲得への突破口とする。

Outline of Final Research Achievements

Previous research aimed at achieving healthy longevity has focused only on the "factors that cause functional decline" in individuals, and has not yet reached a fundamental solution. Therefore, we made a 180-degree turn and focused on the control of potential defense mechanisms.
As a result, it was proven that a similar biological response called "aestivation," which was acquired by organisms to retain body fluid when they landed during evolution, is preserved in mammals, and it was experimentally demonstrated that aestivation-like response regulates body fluid in the pathogenesis of hypertension, kidney disease, and liver failure in rats. Furthermore, dramatic changes in body fluid in mice bred in space have also been demonstrated and are being studied in collaboration with JAXA.

Academic Significance and Societal Importance of the Research Achievements

健康長寿を目指した研究のすべては、個体の機能低下を生じる「要因」を阻害する、あるいは補足して解決を図るものばかりであり、生体が備え持つ適応能力に着目したものは皆無であった。これに対し本研究は、これまでの申請者の発見に基づき、生体が持つ目に見えない生体防御機構である「夏眠様反応」を制御することで老化防止や生活習慣病の未病を試みる世界初の挑戦であり、新しい学術分野を切り開き、健康長寿獲得への突破口とするものである。

Report

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

    (27 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (3 results) Journal Article (13 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 13 results,  Open Access: 10 results) Presentation (8 results) (of which Int'l Joint Research: 4 results,  Invited: 6 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] DUKE-NUS(シンガポール)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] DUKE-NUS(シンガポール)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] DUKE-NUS(シンガポール)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Possible renoprotective mechanisms of SGLT2 inhibitors.2023

    • Author(s)
      Akira Nishiyama, Kento Kitada
    • Journal Title

      Frontiers in Medicine

      Volume: 10 Pages: 1115413-1115413

    • DOI

      10.3389/fmed.2023.1115413

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possible contribution of phosphate to the pathogenesis of chronic kidney disease in dolphins.2023

    • Author(s)
      Nourin Jahan, Hiroyuki Ohsaki, Kiyoko Kaneko, Asadur Rahman, Takeshi Nishiyama, Makoto Koizumi, Shuichiro Yamanaka, Kento Kitada, Yuki Sugiura, Kenji Matsui, Takashi Yokoo, Takayuki Hamano, Makoto Kuro-O, Takuya Itou, Miwa Suzuki, Keiichi Ueda, Akira Nishiyama
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 5161-5161

    • DOI

      10.1038/s41598-023-32399-6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential Impact of Non-Steroidal Mineralocorticoid Receptor Antagonists in Cardiovascular Disease2023

    • Author(s)
      Rahman Asadur、Jahan Nourin、Rahman Md Tanvir、Nishiyama Akira
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 3 Pages: 1922-1922

    • DOI

      10.3390/ijms24031922

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Contributions of renal water loss and skin water conservation to blood pressure elevation in spontaneously hypertensive rats2022

    • Author(s)
      Ogura Takahiro、Kitada Kento、Morisawa Norihiko、Fujisawa Yoshihide、Kidoguchi Satoshi、Nakano Daisuke、Kobara Hideki、Masaki Tsutomu、Titze Jens、Nishiyama Akira
    • Journal Title

      Hypertension Research

      Volume: 46 Issue: 1 Pages: 32-39

    • DOI

      10.1038/s41440-022-01044-6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Blood pressure adaptation in vertebrates: comparative biology2022

    • Author(s)
      Nishiyama Akira、Kitada Kento、Suzuki Miwa
    • Journal Title

      Kidney International

      Volume: 102 Issue: 2 Pages: 242-247

    • DOI

      10.1016/j.kint.2022.03.032

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tolvaptan induces body fluid loss and subsequent water conservation in normal rats2022

    • Author(s)
      Kidoguchi Satoshi、Kitada Kento、Fujisawa Yoshihide、Nakano Daisuke、Yokoo Takashi、Titze Jens、Nishiyama Akira
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 149 Issue: 3 Pages: 115-123

    • DOI

      10.1016/j.jphs.2022.04.008

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hepatocellular carcinoma induces body mass loss in parallel with osmolyte and water retention in rats2022

    • Author(s)
      Kidoguchi Satoshi、Kitada Kento、Nakajima Kazuki、Nakano Daisuke、Ohsaki Hiroyuki、Kittikulsuth Wararat、Kobara Hideki、Masaki Tsutomu、Yokoo Takashi、Takahashi Kazuo、Titze Jens、Nishiyama Akira
    • Journal Title

      Life Sciences

      Volume: 289 Pages: 120192-120192

    • DOI

      10.1016/j.lfs.2021.120192

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Sodium/glucose cotransporter 2 and renoprotection: From the perspective of energy regulation and water conservation.2021

    • Author(s)
      Kento Kitada, Satoshi Kidoguchi, Daisuke Nakano, Akira Nishiyama.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 147 Issue: 3 Pages: 245-250

    • DOI

      10.1016/j.jphs.2021.07.006

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Renal NG2-expressing cells have a macrophage-like phenotype and facilitate renal recovery after ischemic injury2021

    • Author(s)
      Kittikulsuth Wararat、Nakano Daisuke、Kitada Kento、Suzuki Norio、Yamamoto Masayuki、Nishiyama Akira
    • Journal Title

      American Journal of Physiology-Renal Physiology

      Volume: 321 Issue: 2 Pages: F170-F178

    • DOI

      10.1152/ajprenal.00011.2021

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, on sodium dynamics in hypertensive subtotally nephrectomized rats2021

    • Author(s)
      Zhang Anqi、Nakano Daisuke、Morisawa Norihiko、Kitada Kento、Kittikulsuth Wararat、Rahman Asadur、Morikawa Takashi、Konishi Yoshio、Nishiyama Akira
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 146 Issue: 2 Pages: 98-104

    • DOI

      10.1016/j.jphs.2021.03.007

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adaptive physiological water conservation explains hypertension and muscle catabolism in experimental chronic renal failure2021

    • Author(s)
      Kovarik Johannes J.、Morisawa Norihiko、Wild Johannes、Marton Adriana、Takase‐Minegishi Kaoru、Minegishi Shintaro、Daub Steffen、Sands Jeff M.、Klein Janet D.、Bailey James L.、Kovalik Jean‐Paul、Rauh Manfred、Karbach Susanne、Hilgers Karl F.、Luft Friedrich、Nishiyama Akira、Nakano Daisuke、Kitada Kento、Titze Jens
    • Journal Title

      Acta Physiologica

      Volume: 00 Issue: 1

    • DOI

      10.1111/apha.13629

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cardioprotective Effects of a Nonsteroidal Mineralocorticoid Receptor Blocker, Esaxerenone, in Dahl Salt-Sensitive Hypertensive Rats2021

    • Author(s)
      Rahman Asadur、Sawano Tatsuya、Sen Anupoma、Hossain Akram、Jahan Nourin、Kobara Hideki、Masaki Tsutomu、Kosaka Shinji、Kitada Kento、Nakano Daisuke、Imamura Takeshi、Ohsaki Hiroyuki、Nishiyama Akira
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 4 Pages: 2069-2069

    • DOI

      10.3390/ijms22042069

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Organ protection by SGLT2 inhibitors: role of metabolic energy and water conservation2020

    • Author(s)
      Marton Adriana、Kaneko Tatsuroh、Kovalik Jean-Paul、Yasui Atsutaka、Nishiyama Akira、Kitada Kento、Titze Jens
    • Journal Title

      Nature Reviews Nephrology

      Volume: 17 Issue: 1 Pages: 65-77

    • DOI

      10.1038/s41581-020-00350-x

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 高食塩接種が各骨のナトリウム・カリウム含量に与える影響2023

    • Author(s)
      北田 研人,宗定 優紘,中野 大介,西山 成
    • Organizer
      第52回日本心脈管作動物質学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] シン・ナトリウム調節2022

    • Author(s)
      西山 成
    • Organizer
      第52回日本腎臓学会西部学術大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] New salt concept and significance of MR inhibition.2022

    • Author(s)
      Akira Nishiyama
    • Organizer
      The 29th Scientific Meeting of the International Society of Hypertension.
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Effects of an SGLT2 inhibitor on salt sensitivity of blood pressure and sympathetic nerve activity in a non-diabetic rat model of chronic kidney disease.2021

    • Author(s)
      Wan N, Rahman A, Nishiyama A.
    • Organizer
      International Society of Hypertension.
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pathophysiological mechanism of mineralocorticoid receptor-dependent chronic kidney disease.2021

    • Author(s)
      Nishiyama A.
    • Organizer
      The 19th International Symposium on Atherosclerosis.
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] New concept of salt and water balance2020

    • Author(s)
      Akira Nishiyama
    • Organizer
      CVMW2020心血管代謝週間(第28回日本血管生物医学会学術集会, 第24回日本心血管内分泌代謝学会学術総会, 第37回国際心臓研究学会日本部会, International Society for Applied Cardiovascular Biology (ISACB)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 皮膚におけるナトリウム貯留と電解質調節2020

    • Author(s)
      西山 成
    • Organizer
      第63回日本腎臓学会学術総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 塩と病態生理・MR阻害薬,2020

    • Author(s)
      西山 成,北田研人
    • Organizer
      第63回日本糖尿病学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Book] エース薬理学2020

    • Author(s)
      金井好克、安西尚彦、安藤 仁、浅井 聰・編
    • Total Pages
      303
    • Publisher
      南山堂
    • ISBN
      9784525140717
    • Related Report
      2020 Research-status Report
  • [Remarks] 香川大学医学部薬理学ホームページ

    • URL

      http://www.kms.ac.jp/%7Eyakuri/

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
  • [Remarks] 香川大学医学部薬理学ホームページ

    • URL

      http://www.kms.ac.jp/%7Eyakuri/4-1_paper.html

    • Related Report
      2020 Research-status Report

URL: 

Published: 2020-08-03   Modified: 2024-01-30  

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