Endocrine Regulation of Survival Responses in C. elegans

描述（由申请人提供）：环境压力触发促生存反应，减缓生长和衰老，并提高动物的抗压力能力。In C.在线虫中，保守的胰岛素/IGF-1样和类固醇信号传导功能一致地调节这些反应。我们感兴趣的是这些内分泌事件是如何在生物体水平上调节的。有新的证据表明，抗衰老和促衰老的类固醇都是在C。优雅这一激素途径的许多组成部分，包括类固醇生成蛋白和类固醇中间体，尚未确定。在这项研究中，我们将调查一个家庭的3个关键类固醇生成酶和一个细胞内胆固醇转运蛋白在抗衰老和促衰老类固醇信号的参与。采用类固醇喂养方法，我们将预测哪种类型的类固醇可能被用作长寿激素。我们将进一步研究这些类固醇信号如何与胰岛素通路交叉的机制。在一项平行的初步研究中，我们已经使用两个全基因组RNAi筛选确定了类固醇和胰岛素信号传导的8种常见修饰剂。我们将研究这些候选基因如何在乳腺癌介导的寿命调节和其他类型的促生存反应中发挥作用。

DESCRIPTION (provided by applicant): Environmental stresses trigger pro-survival responses that slow down growth and aging, and increase stress resistance in animals. In C. elegans, conserved insulin/IGF-1-like and steroid signaling function in concert to regulate these responses. We are interested in how these endocrine events are regulated at the organismal level. There is emerging evidence showing that both anti-aging and pro-aging steroids are made in C. elegans. Many components of this hormonal pathway, including steroidogenic proteins and steroid-intermediates, have yet to be identified. In this study, we will investigate the involvement of a family of 3 key steroidogenic enzymes and one intracellular cholesterol transporter in anti- and pro-aging steroid signaling. Employing sterol-feeding methodology, we will predict which types of steroids might be utilized as longevity hormones. We will further investigate the mechanisms of how these steroid signals intersect with the insulin pathway. In a parallel preliminary study, we have identified 8 common modifiers of steroid and insulin signaling using two whole-genome RNAi screens. We will investigate how these candidate genes function in hormone-mediated lifespan regulation and other types of pro-survival responses.