Modulation and/or controlling of the aging event by the basic anti-oxidative response with environmental transcriptional factor Nrf1
Project/Area Number |
16H05922
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Single-year Grants |
Research Field |
Applied health science
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Research Institution | Saga University |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2016: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
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Keywords | 老化 / 酸化ストレス / Nrf1 / ストレス / 加齢・老化 / レドックスバランス |
Outline of Final Research Achievements |
We have been studying that the relationship between aging and environmental transcriptional factor, Nrf1, using genetical modified mouse and zebrafish. Especially, we have found that genetical aging model mice, Klotho-knockout mice with modulate the Nrf1 expression profile could live longer compared with single klotho knockout mice. Consequently, Klotho-/- :: Nrf1-knockdown mice were lived 20 weeks after birth. From those experiment we have identified 9 aging surrogate genetical marker which can explain the aging stage. We have tried to generate overexpress and/or knockout zebrafish model for those genes. As a consequence, we have already identified that serpina 4 and ccl4 knockout fish showed early aging phenotype. In addition, from metabolomic analysis compared with wild type, klotho knockout mouse and natural aging mice (over 3-years-old), we have identified that polyamine pathway have a several contribution to prevention of the aging phenotype.
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Academic Significance and Societal Importance of the Research Achievements |
タンパク質の機能不全は老化だけではなく、数々の疾患の原因となることが知られている。環境応答転写因子Nrf1はこれらの不良タンパク質除去に効果があると近年注目さレテいる。本研究では、老化によって蓄積することを見出したことから、Nrf1タンパク質量を是正することで老化が制御できることを遺伝的に明確にできたことは大きな成果といえる。現時点では、Nrf1の下流でどの標的遺伝子が真の老化抑制かを示すことはできていないが、今後、遺伝子改変動物を用いて老化現象を明確にし、そのタンパク質を制御する化合物や食品由来天然物を取得することにより、老化抑制のコンセプトを提唱することを目指している。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Furan- and Thiophene-2-Carbonyl Amino Acid Derivatives Activate Hypoxia-Inducible Factor via Inhibition of Factor Inhibiting Hypoxia-Inducible Factor-12018
Author(s)
Kawaguchi Shin-Ichi, Gonda Yuhei, Yamamoto Takuya, Sato Yuki, Shinohara Hiroyuki, Kobiki Yohsuke, Ichimura Atsuhiko, Dan Takashi, Sonoda Motohiro, Miyata Toshio, Ogawa Akiya, Tsujita Tadayuki
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Journal Title
Molecules
Volume: 23
Issue: 4
Pages: 885-885
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Halofuginone enhances the chemo-sensitivity of cancer cells by suppressing NRF2 accumulation.2017
Author(s)
Tsuchida K, Tsujita T, Hayashi M, Ojima A, Keleku-Lukwete N, Katsuoka F, Otsuki A, Kikuchi H, Oshima Y, Suzuki M, Yamamoto M.
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Journal Title
Free Radic Biol Med
Volume: 103
Pages: 236-247
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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