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Research on the effects and mechanisms of molecular hydrogen on immune homeostasis in aging and related diseases

Research Project

Project/Area Number 20H04136
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

Ohsawa Ikuroh  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, 研究副部長 (30343586)

Co-Investigator(Kenkyū-buntansha) 藤田 泰典  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, 研究員 (30515888)
池谷 真澄  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, 研究員 (60644359)
伊藤 雅史  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, 研究員 (80393114)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords水素分子 / 酸化ストレス / 炎症 / 動物モデル / 脳細胞死 / 腸管免疫系 / 大動脈解離 / リン脂質 / 分子状水素 / 培養細胞 / リピドーム / メタボローム / 水素ガス / 老化 / ミトコンドリア / 免疫恒常性 / 水素吸入療法 / 臨床研究 / 疾患動物モデル / 細胞応答 / 水素 / エンドソーム / 水素ガス吸引療法
Outline of Research at the Start

本研究は、水素分子による細胞ストレス防御機構と免疫恒常性維持のメカニズムを分子レベルと個体レベルで明らかにし、水素分子の効果的利用による健康長寿の促進を目指す。培養細胞での水素分子添加による脂質変動を網羅的に解析し、生体膜や細胞内輸送およびオルガネラの機能変化との関連を明らかにする。個体レベルでは水素分子が作用する臓器と細胞を示し、免疫恒常性維持に関与する細胞内外のシグナル分子を明らかする。さらに疾患応用に向けて高齢者の非感染性炎症の緩和を目指した水素ガス療法の臨床研究を進める。

Outline of Final Research Achievements

Culturing neuroblastoma cells in the presence of hydrogen transiently increased certain phospholipids and broadly inhibited energy metabolic pathways. Simultaneously elevated oxidative stress may elicit an adaptive response in the cells. Hydrogen gas inhalation inhibited neural stem cell death in the brains of juvenile mice induced by anesthetic gas inhalation. c-Jun activation was inhibited. A single administration of hydrogen water to a mouse model of colitis for several days alleviated the pathological condition and inhibited the decrease of regulatory T cells in the small intestinal Peyer's patches. Furthermore, presentation of food antigens to dendritic cells was also inhibited, suggesting that hydrogen water contributes to the homeostasis of the intestinal immune system. In clinical studies, we have already completed safety studies of hydrogen gas inhalation therapy in several patients with acute aortic dissection.

Academic Significance and Societal Importance of the Research Achievements

水素分子による一過的な脂質変化が細胞に軽度ストレスを生じさせ適応応答を引き起こすことが、水素ガス吸入により炎症が抑制される分子機序の一端であり、臨床での水素ガス吸入療法へとつながる。また、動物モデルで水素水を単回摂取させると小腸で腸管免疫系の恒常性につながる変化が生じた。すでに知られている水素水の多様な疾患抑制効果や抗疲労効果についての機序を解明する重要な発見である。

Report

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

    (44 results)

All 2023 2022 2021 2020 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 6 results) Presentation (27 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Remarks (2 results)

  • [Journal Article] H<sub>2</sub>-induced transient upregulation of phospholipids with suppression of energy metabolism2023

    • Author(s)
      Ohsawa Ikuroh、Iketani Masumi、Sakane Iwao、Fujita Yasunori、Ito Masafumi
    • Journal Title

      Medical Gas Research

      Volume: 13 Issue: 3 Pages: 133-133

    • DOI

      10.4103/2045-9912.344973

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Temporal changes in mitochondrial function and reactive oxygen species generation during the development of replicative senescence in human fibroblasts2022

    • Author(s)
      Fujita Yasunori、Iketani Masumi、Ito Masafumi、Ohsawa Ikuroh
    • Journal Title

      Experimental Gerontology

      Volume: 165 Pages: 111866-111866

    • DOI

      10.1016/j.exger.2022.111866

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Drinking hydrogen water improves photoreceptor structure and function in retinal degeneration 6 mice2022

    • Author(s)
      Igarashi Tsutomu、Ohsawa Ikuroh、Kobayashi Maika、Miyazaki Kai、Igarashi Toru、Kameya Shuhei、Shiozawa Asaka Lee、Ikeda Yasuhiro、Miyagawa Yoshitaka、Sakai Mashito、Okada Takashi、Sakane Iwao、Takahashi Hiroshi
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 13610-13610

    • DOI

      10.1038/s41598-022-17903-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of proton pumping on the structural rigidity of cristae in mitochondria2022

    • Author(s)
      Yoneda Mayu、Aklima Jannatul、Ohsawa Ikuroh、Ohta Yoshihiro
    • Journal Title

      Archives of Biochemistry and Biophysics

      Volume: 720 Pages: 109172-109172

    • DOI

      10.1016/j.abb.2022.109172

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene therapy of prostate cancer using liposomes containing perforin expression vector driven by the promoter of prostate-specific antigen gene2022

    • Author(s)
      Kosuke Mizutani, Kyojiro Kawakami, Yasunori Fujita, Taku Kato, Manabu Takai, Daiki Kato, Koji Iinuma, Takuya Koie, Masafumi Ito
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 1442-1442

    • DOI

      10.1038/s41598-021-03324-6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Muscle fiber type specific alterations of mitochondrial respiratory function and morphology in aged female mice2021

    • Author(s)
      Fukunaga Taichi、Mori Shuuichi、Omura Takuya、Noda Yoshihiro、Fujita Yasunori、Ohsawa Ikuroh、Shigemoto Kazuhiro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 540 Pages: 116-122

    • DOI

      10.1016/j.bbrc.2020.11.071

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diagnostic potential of serum extracellular vesicles expressing prostate-specific membrane antigen in urologic malignancies.2021

    • Author(s)
      Kawakami, K. Fujita, Y. Kato, T. Horie, K. Koie, T. Umezawa, K. Tsumoto, H. Miura, Y. Katagiri, Y. Miyazaki, T. Ohsawa, I. Mizutani, K. Ito, M.
    • Journal Title

      Sci Rep

      Volume: 11 Issue: 1 Pages: 15000-15000

    • DOI

      10.1038/s41598-021-94603-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury2021

    • Author(s)
      Aokage Toshiyuki、Seya Mizuki、Hirayama Takahiro、Nojima Tsuyoshi、Iketani Masumi、Ishikawa Michiko、Terasaki Yasuhiro、Taniguchi Akihiko、Miyahara Nobuaki、Nakao Atsunori、Ohsawa Ikuroh、Naito Hiromichi
    • Journal Title

      BMC Pulmonary Medicine

      Volume: 21 Issue: 1 Pages: 339-339

    • DOI

      10.1186/s12890-021-01712-2

    • NAID

      120007170516

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proteomic analysis of extracellular vesicles identified PI3K pathway as a potential therapeutic target for cabazitaxel‐resistant prostate cancer2021

    • Author(s)
      Hishida Seiji、Kawakami Kyojiro、Fujita Yasunori、Kato Taku、Takai Manabu、Iinuma Koji、Nakane Keita、Tsuchiya Tomohiro、Koie Takuya、Miura Yuri、Ito Masafumi、Mizutani Kosuke
    • Journal Title

      The Prostate

      Volume: 81 Issue: 9 Pages: 592-602

    • DOI

      10.1002/pros.24138

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Profiling of Serum Extracellular Vesicles Reveals miRNA-4525 as a Potential Biomarker for Advanced Renal Cell Carcinoma2021

    • Author(s)
      MURAMATSU-MAEKAWA YUKA、KAWAKAMI KYOJIRO、FUJITA YASUNORI、TAKAI MANABU、KATO DAIKI、NAKANE KEITA、KATO TAKU、TSUCHIYA TOMOHIRO、KOIE TAKUYA、MIURA YURI、ITO MASAFUMI、MIZUTANI KOSUKE
    • Journal Title

      Cancer Genomics - Proteomics

      Volume: 18 Issue: 3 Pages: 253-259

    • DOI

      10.21873/cgp.20256

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biological Responses to Hydrogen Molecule and its Preventive Effects on Inflammatory Diseases2021

    • Author(s)
      Ohsawa Ikuroh
    • Journal Title

      Current Pharmaceutical Design

      Volume: 27 Issue: 5 Pages: 659-666

    • DOI

      10.2174/1381612826666200925123510

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Astaxanthin improves osteopenia caused by aldehyde-stress resulting from Aldh2 mutation due to impaired osteoblastogenesis2020

    • Author(s)
      Hoshi H, Monoe F, Ohsawa I, Ohta S, Miyamoto T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 527 Issue: 1 Pages: 270-275

    • DOI

      10.1016/j.bbrc.2020.04.013

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hydrogen promotes the activation of Cu, Zn superoxide dismutase in a rat corneal alkali-burn model2020

    • Author(s)
      Arima T, Igarashi T, Uchiyama M, Kobayashi M, Ohsawa I, Shimizu A, Takahashi H
    • Journal Title

      International Journal of Ophthalmology

      Volume: 13 Issue: 8 Pages: 1173-1179

    • DOI

      10.18240/ijo.2020.08.01

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum growth differentiation factor 15 level is associated with muscle strength and lower extremity function in older patients with cardiometabolic disease2020

    • Author(s)
      Oba Kazuhito, Ishikawa Joji, Tamura Yoshiaki, Fujita Yasunori, Ito Masafumi, Iizuka Ai, Fujiwara Yoshinori, Kodera Remi, Toba Ayumi, Toyoshima Kenji, Chiba Yuko, Mori Seijiro, Tanaka Masashi, Ito Hideki, Harada Kazumasa, Araki Atsushi
    • Journal Title

      Geriatrics &amp; Gerontology International

      Volume: 20 Issue: 10 Pages: 980-987

    • DOI

      10.1111/ggi.14021

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial stress and GDF15 in the pathophysiology of sepsis2020

    • Author(s)
      Fujita Yasunori、Ito Masafumi、Ohsawa Ikuroh
    • Journal Title

      Archives of Biochemistry and Biophysics

      Volume: 696 Pages: 108668-108668

    • DOI

      10.1016/j.abb.2020.108668

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] Drinking hydrogen water improves photoreceptor structure and function in retinal degeneration 6 mice2023

    • Author(s)
      Shuhei Kameya, Tsutomu Igarashi, Ikuroh Ohsawa, Maika Kobayashi, Kai Miyazaki, Toru Igarashi, Asaka Lee Shiozawa, Yasuhiro Ikeda, Yoshitaka Miyagawa, Mashito Sakai, Takashi Okada, Iwao Sakane, Hiroshi Takahashi
    • Organizer
      The 60th ISCEV symposium
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ミトコンドリア翻訳阻害によるヒト胎児繊維芽細胞の分裂寿命延伸2023

    • Author(s)
      藤田泰典,池谷真澄,伊藤雅史,大澤郁朗
    • Organizer
      第21回日本ミトコンドリア学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 水素ガス投与はセボフルランによって誘導される新生仔マウス脳のc-Jun活性化とアポトーシスを抑制する2022

    • Author(s)
      池谷真澄,羽富舞,藤田泰典,渡辺信博,堀田晴美,伊藤雅史,川口英夫,大澤郁朗
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 高濃度水素水投与による小腸パイエル板での卵白アルブミン取り込み抑制2022

    • Author(s)
      横山茜,池谷真澄,藤田泰典,伊藤雅史,川口英夫,大澤郁朗
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ヒト胎児線維芽細胞の分裂寿命に対するミトコンドリア呼吸鎖阻害の効果2022

    • Author(s)
      藤田泰典、池谷真澄、伊藤雅史、大澤郁朗
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 老齢・リポ多糖 (LPS)投与マウスへの水素ガス吸入が肺・肝に与える影響2022

    • Author(s)
      青景聡之, 池谷真澄, 瀬谷海月, 大澤郁朗, 内藤宏道, 中尾篤典
    • Organizer
      第50回日本救急医学会総会・学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 水素ガスはc-Jun抑制を介してセボフルランによる新生仔マウスの脳細胞死を抑制する2022

    • Author(s)
      池谷真澄、羽富舞、藤田泰典、渡辺信博、堀田晴美、伊藤雅史、川口英夫、大澤郁朗
    • Organizer
      第11回日本分子状水素医学生物学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 小腸パイエル板での水素水投与による卵白アルブミン取り込み抑制2022

    • Author(s)
      横山茜、上田優依、濱美里、池谷真澄、藤田泰典、伊藤雅史、川口英夫、大澤郁朗
    • Organizer
      第11回日本分子状水素医学生物学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 分子状水素医学の過去・現在・未来2022

    • Author(s)
      大澤郁朗
    • Organizer
      第11回日本分子状水素医学生物学会大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Doxycycline extends replicative lifespan in human fibroblast TIG-1.2022

    • Author(s)
      Yasunori Fujita, Masumi Iketani, Masasumi Ito, Ikuroh Ohsawa
    • Organizer
      第45回日本基礎老化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Optimal concentration of hydrogen gas attenuates sevoflurane-induced brain cell death in juvenile mice2022

    • Author(s)
      Masumi Iketani, Mai Hatomi, Yasunori Fujita, Nobuhiro Watanabe, Harumi Hotta, Masasumi Ito, Hideo Kawaguchi, Ikuroh Ohsawa.
    • Organizer
      第45回日本基礎老化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 分子状水素による老化制御の可能性2022

    • Author(s)
      大澤郁朗
    • Organizer
      第30回日本病態生理学会大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Delayed endosomal transport with lipid compositional change in molecular hydrogen-treated neuroblastoma2021

    • Author(s)
      池谷真澄、坂根巌、藤田泰典、伊藤雅史、大澤郁朗
    • Organizer
      第44回日本基礎老化学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Mitochondrial dysfunction is not a key initiator of replicative senescence2021

    • Author(s)
      藤田泰典、池谷真澄、伊藤雅史、大澤郁朗
    • Organizer
      第44回日本基礎老化学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Muscle fiber type specific alterations of mitochondrial respiratory function and morphology2021

    • Author(s)
      重本和宏、福永大地、森秀一、大村卓也、野田義博、藤田泰典、大澤郁朗
    • Organizer
      第44回日本基礎老化学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 分子状水素の作用機序についての考察2021

    • Author(s)
      大澤郁朗
    • Organizer
      第10回日本分子状水素医学生物学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 分子状水素による一過的なリン脂質増加とエネルギー代謝抑制2021

    • Author(s)
      池谷真澄、坂根巌、藤田泰典、伊藤雅史、大澤郁朗
    • Organizer
      第10回日本分子状水素医学生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 加齢マウスにおける筋線維タイプ別のミトコンドリア呼吸機能および形態の変化2021

    • Author(s)
      重本和宏、福永大地、森秀一、大村卓也、野田義博、藤田泰典、大澤郁朗
    • Organizer
      第94回日本生化学大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 分子状水素の作用メカニズムを考える2021

    • Author(s)
      大澤郁朗
    • Organizer
      日本ビタミン学会第73回大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 水素水飲用はDSSによる小腸パイエル板制御性T細胞障害を抑制する2021

    • Author(s)
      横山茜、小松真希、池谷真澄、藤田泰典、川口英夫、大澤郁朗
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 分子状水素は一過的なリン脂質増加とエネルギー代謝抑制を誘導する2021

    • Author(s)
      池谷真澄、坂根巌、藤田泰典、伊藤雅史、大澤郁朗
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ミトコンドリア機能障害は複製老化初期プロセスの主要な因子ではない2021

    • Author(s)
      藤田泰典、池谷真澄、伊藤雅史、大澤郁朗
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Mitochondrial dysfunction is not involved in the initiation of replicative senescence2020

    • Author(s)
      Yasunori Fujita, Masumi Iketani, Masafumi Ito, and Ikuroh Ohsawa.
    • Organizer
      第43回日本基礎老化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Effect of drinking hydrogen water on intestional immunity in colitis mouse model2020

    • Author(s)
      Masaki Komatsu, Masumi Iketani, Yasunori Fujita, Hideo Kawaguchi, Ikuroh Ohsawa
    • Organizer
      第43回日本基礎老化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Molecular hydrogen administration promotes lipids change and endosomal vesicles increase2020

    • Author(s)
      Iketani M, Sakane I, Fujita Y, Ito M, Ohsawa I
    • Organizer
      第43回日本基礎老化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 培養細胞への分子状水素投与はホスファチジルセリン増加を伴いエンドソーム輸送を抑制する2020

    • Author(s)
      Masumi Iketani, Iwao Sakane, Yasunori Fujita, Masafumi Ito, Ikuroh Ohsawa
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Suppression of DSS-induced Treg activation by drinking of hydrogen-rich water in small intestinal Peyer’s patches2020

    • Author(s)
      Masaki Komatsu, Masumi Iketani, Yasunori Fujita, Hideo Kawaguchi, Ikuroh Ohsawa
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
  • [Remarks] 生体調節機能研究

    • URL

      https://www.tmghig.jp/research/team/roukaseigyo/seitaichousetsukinou/

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
  • [Remarks] ミトコンドリアと水素の世界

    • URL

      https://www.youtube.com/watch?v=SSInX_pCL_4

    • Related Report
      2021 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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