Aging, the progressive degeneration of body and mind, is a universal problem marked by a decline in tissue organization and function, and an increase in the likelihood of death. Progress in understanding the cellular and molecular basis of aging is rapidly accelerating, following the discovery that several well-known model organisms age in many of the same ways as humans. In addition to their contributions to our basic understanding of the biology of aging, these organisms are now being used to screen for compounds that extend not only lifespan, but also the quality of life in older individuals (health span). One of the most powerful model systems in aging and health span research is the microscopic nematode Caenorhabditis elegans, favored for its short lifespan (2-3 weeks), genetic tractability, and low cost. C. elegans research is currently undergoing rapid innovation as its small size is particularly compatible with microfluidics - the manipulation of fluids in channels with dimensions of tens of micrometers. The overall goal of the proposed research is to accelerate the discovery of compounds that extend health span through the development of a novel microfluidic device that is likely to enhance the throughput and resolution of health span screening in this key organism. The conventional method of health span screening in C. elegans currently faces three critical barriers: the absence of rigorously standardized growth conditions, the difficulty of making repeated measurements on identified individuals, and the challenge of high-throughput quantification of feeding behavior, one of the most reliable measures of health in the worm. The proposed research takes a head-on approach to these challenges by combining, into a single device, two previously established microfluidic technologies, one for long-term culture of large numbers of individually isolated worms, and one for making non-invasive electrical recordings of feeding behavior. Phase I of the proposed research seeks fundamental proof of concept for the combined device. Phase II of the project extends this work by automating health- span screens and increasing their throughput.
Americans aged 85 or older constitute the fastest growing segment of the U.S. population, but the genetic and biological basis of aging and associated conditions is poorly understood. The project develops new technology for discovering drugs that prolong life and mitigate the detrimental effects of aging.