High-throughput multi-modal analysis of natural variation in C. elegans healthspan

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PROJECT SUMMARY A substantial fraction of the variation in aging can be explained by genetics, but little is known about what these genetic factors are and how they modulate healthy aging. Much of our fundamental understanding of mechanisms that modulate aging, including insulin signaling and proteostasis pathways, come from the study of the model nematode Caenorhabditis elegans. Nearly all C. elegans aging studies use a single laboratory- adapted strain with little connection to natural variation. In this project we aim to establish C. elegans as a model for natural variation in aging. First we will develop a system for multi-modal automated healthspan assays based on a previously developed `WorMotel' microfabricated multi-well imaging platform. Second, we will carry out longitudinal assays on 16 genotypically diverged wild-isolate C. elegans strains to determine traits correlated with healthspan decline. Our results will set the stage for comprehensive mechanistic analysis of genes underlying natural variation in aging. The combination of high-throughput healthspan analysis and quantitative genetics methods will be particularly powerful for delineating genetic causes of a complex healthspan phenotype, providing the first mechanistic understanding of natural variation in metazoan aging.