| Project/Area Number |
17K19227
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Agricultural chemistry and related fields
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| Research Institution | Nagoya University |
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Principal Investigator |
AIBA Hirofumi 名古屋大学, 創薬科学研究科, 教授 (60211687)
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
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| Keywords | 分裂酵母 / 細胞寿命 / 寿命 / 老化 |
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| Outline of Final Research Achievements |
"How is lifespan determined?" is one of the themes that should be solved. To understand the longevity of humans and other higher animals, it is essential to understand the longevity at the cellular level. Then I attempted to elucidate the control mechanism of cellular longevity using fission yeast as a model. As a result, the following new findings were obtained. (1) Caloric restriction was the only known lifespan-extending signal, but in this study, we found sulfur depletion as a new lifespan-extending signal. (2) Sulfur depletion induced the expression of Ecl1 (extender of chronological lifespan 1) that was discovered by the applicant, and found that the lifespan extension by sulfur depletion depends on the Ecl1 family. (3) Sulfur depletion reduced ribosome expression in an Ecl1 family-dependent manner, suggesting that this is the reason for the extension of lifespan. We have accumulated important knowledge for the development of human health and longevity drug discovery.
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| Academic Significance and Societal Importance of the Research Achievements |
「寿命がいかにして決まるのか？」を解明することは健康長寿社会を実現する上でも重要である。ヒトを始めとする高等動物の寿命を理解するためには、まず細胞レベルで寿命を理解することが必須となる。そこで申請者は、分裂酵母をモデルに細胞寿命の制御機構を解明することに挑戦した。その結果、これまで唯一知られていたカロリー制限以外に、新たな寿命延長シグナルとして硫黄の枯渇を見出した。加えて、リボソームの量的・質的変化（翻訳活性変化）が寿命を制御する可能性を示した。これらの成果によって、ヒトの健康長寿に貢献する創薬ターゲットを見出し健康長寿創薬を展開するための基盤的知識を蓄積することができた。
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