High-throughput Imaging of Lifespan and Healthspan in C. Elegans
2013 new Scholar Award in aging
Over the past several decades, studies using model organisms have yielded insights into the basic biological mechanisms of aging. In particular, research with the roundworm C. elegans, aided by its short lifespan and easily manipulated genetics, has identified a number of pathways that regulate aging, such as insulin/insulin-like signaling, dietary restriction, heat shock resistance, and reproductive and sensory signaling pathways. Subsequent work has shown that similar processes also regulate lifespan in other animals. While most C. elegans aging research has focused on measurement of lifespan as the outcome, lifespan is only one point—the endpoint— of a complex set of time-dependent physiological processes that depends on genetic, environmental, and random factors. Longitudinal measurements of physiology and/or behavior on an individual animal basis would give a much richer phenotypic description of aging mutants. Greater attention to behavioral outcomes is critical for aging research’s ultimate goal of increasing not only lifespan but healthspan, the period over which the quality of life remains high. In this project, we will develop and apply innovative technologies for high-throughput measurement of C. elegans behavior and lifespan. We will design and construct microfabricated multi-well devices optimized for worm cultivation and imaging, and use them with custom machine vision systems to record the behavioral and aging trajectories of hundreds of thousands of individual wild-type and mutant worms. We will apply this method to investigate the mechanisms of behavioral decline, and its variability, during aging. By performing a series of forward and reverse genetic screens, we will test the hypothesis that lifespan and healthspan, and the variabilities in either, are under partially independent genetic control. Our work will not only address fundamental questions about the mechanisms of aging, but also provide a platform to greatly accelerate C. elegans aging research. To that end, we will work to openly disseminate our protocols, hardware, and software to the C. elegans research community.