Endocrine Regulation of Survival Responses in C. elegans

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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. PUBLIC HEALTH RELEVANCE: We intend to determine the function of new steroid signaling components in longevity regulation. We will further use the mutants of these components to investigate anti-aging steroid hormones in C. elegans. We will also briefly characterize 8 shared modifiers of steroid and insulin signaling.