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Development of a bioassay to screen for chemicals mimicking the anti-aging effects of calorie restriction
http://hdl.handle.net/10069/24490
http://hdl.handle.net/10069/2449052315169-0767-46a4-a4ec-7347f2072b87
名前 / ファイル | ライセンス | アクション |
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BBRC401_213.pdf (452.2 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2010-11-24 | |||||
タイトル | ||||||
タイトル | Development of a bioassay to screen for chemicals mimicking the anti-aging effects of calorie restriction | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Aging | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Biosensing | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Calorie restriction | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Drug discovery | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Metabolism | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Chiba, Takuya
× Chiba, Takuya× Tsuchiya, Tomoshi× Komatsu, Toshimitsu× Mori, Ryoichi× Hayashi, Hiroko× Shimano, Hitoshi× Spindler, Stephen R.× Shimokawa, Isao |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Suppression of the growth hormone/insulin-like growth factor-I pathway in Ames dwarf (DF) mice, and caloric restriction (CR) in normal mice extends lifespan and delays the onset of age-related disorders. In combination, these interventions have an additive effect on lifespan in Ames DF mice. Therefore, common signaling pathways regulated by DF and CR could have additive effects on longevity. In this study, we tried to identity the signaling mechanism and develop a system to assess pro-longevity status in cells and mice. We previously identified genes up-regulated in the liver of DF and CR mice by DNA microarray analysis. Motif analysis of the upstream sequences of those genes revealed four major consensus sequence motifs, which have been named dwarfism and calorie restriction-responsive elements (DFCR-REs). One of the synthesized sequences bound to hepatocyte nuclear factor-4α (HNF-4α), an important transcription factor involved in liver metabolism. Furthermore, using this sequence information, we developed a highly sensitive bioassay to identify chemicals mimicking the anti-aging effects of CR. When the reporter construct, containing an element upstream of a secreted alkaline phosphatase (SEAP) gene, was co-transfected with HNF-4α and its regulator peroxisome proliferator-activated receptor (PPAR) γ coactivator-1α (PGC-1α), SEAP activity was increased compared with untransfected controls. Moreover, transient transgenic mice established using this construct showed increased SEAP activity in CR mice compared with ad libitum-fed mice. These data suggest that because of its rapidity, ease of use, and specificity, our bioassay will be more useful than the systems currently employed to screen for CR mimetics, which mimic the beneficial effects of CR. Our system will be particularly useful for high-throughput screening of natural and synthetic candidate molecules. | |||||
書誌情報 |
Biochemical and Biophysical Research Communications 巻 401, 号 2, p. 213-218, 発行日 2010-10-15 |
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出版者 | ||||||
出版者 | Elsevier Inc. | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0006291X | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 10902104 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA00564395 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.bbrc.2010.09.032 | |||||
権利 | ||||||
権利情報 | Copyright © 2010 Elsevier Inc. All rights reserved. | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Biochemical and Biophysical Research Communications, 401(2), pp.213-218; 2010 |