| Project/Area Number |
18K02231
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 08030:Family and consumer sciences, and culture and living-related
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| Research Institution | Yamanashi Gakuin University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
萱嶋 泰成 山梨学院短期大学, その他部局等, 教授(移行) (90365453)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | HDAC / リグナン / skn-1 / pmk-1 / 寿命延長 / hda-2 / pml-1 / ヒストンアセチル化 / ポリフェノール |
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| Outline of Final Research Achievements |
We have found a lignan compound derived from plum as a food ingredient having an anti-aging effect through the regulation of histone deacetylation. These lignan compounds activated HDACs belonging to class I. Therefore, when we examined Class I HDACs involved in extending the lifespan of C. elegans, it became clear that activation of HDACs 1, 2, and 3 was involved in extending the lifespan. Secoisolariciresinol and pinoresinol of plum lignans enhance HDAC activity and activate or induce expression of pmk-1 by promoting histone deacetylase, and then skn-1 is translocated into the nucleus to extend its lifespan. It is considered that the life span is extended by enhancing the expression of genes related to sod-1 and gcs-1.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでに報告されているレスベラトロールによるサーチュインの活性化は、直接寿命の延伸に結びつくわけではなく、一定の条件下（カロリー制限下）での効果・作用であった。今回我々の見出した梅由来のリグナン化合物は、HDACを介して遺伝子発現を調節し、寿命の延伸を導いていた。この作用機序は、これまでと異なる新規なアンチエイジングシグナルである。また、HDACの活性を調節する成分を探索することで、寿命の延伸に効果を発揮する成分が見出せる新たな評価系を確立した。この手法により、効率的に有効成分の探索が行えるものと考えられる。
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