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.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01AG033598-05
Application #
8738555
Study Section
Cellular Mechanisms in Aging and Development Study Section (CMAD)
Program Officer
Finkelstein, David B
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Washington
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98195
Promislow, Daniel E L; Kaeberlein, Matt (2014) Development. Chemical warfare in the battle of the sexes. Science 343:491-2
Kaeberlein, Matt (2013) Longevity and aging. F1000Prime Rep 5:5