Development of a bioassay to screen for chemicals mimicking the anti-aging effects of calorie restriction
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概要
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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.
- 2010-10-15
論文 | ランダム
- 坂東眞理子 特別指南 「団塊の世代の品格」7か条 (男の生き方講座)
- 基調講演 女性の品格と住まい (第19回住生活月間協賛 まちなみシンポジウム)
- ココだけで教えて!(第15回)ゲスト 坂東眞理子さん(昭和女子大学学長) 弱い者をいじめない、強い者に媚びない。それが男性の「品格」なのだと思います
- 極微量不純物の検出に 固体用質量分析計 (金属計測機器の実際 各種試験機を正しく使うために)
- 蟲 : mushi