Modulation and/or controlling of the aging event by the basic anti-oxidative response with environmental transcriptional factor Nrf1

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05922
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Applied health science
• Research Institution: Saga University
• Principal Investigator: Tsujita Tadayuki 佐賀大学, 農学部, 講師 (20622046)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 老化 / 酸化ストレス / Nrf1

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.

Free Research Field

老化、遺伝子改変動物

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。