Logarithmic bacterial gradient chip for analyzing the effects of dietary restriction on C. elegans growth

Abstract

C. elegans is a commonly used model organism for studying the basic mechanisms of lifespan extension by dietary restriction (DR). Progress has been limited, however, by the lack of an automated system for quantitative analysis of this effect of bacterial diet. In this work, multifunctional logarithmic gradient-customizing microfluidic device, which takes advantage of hydrodynamics, was developed to long-term maintain worm culture on the chip with parallel live imaging and generate logarithmic concentration gradient of bacteria. We successfully employed this platform to investigate the longevity and stress response of the worms in response to various concentrations of bacterial food. The results indicated that the lifespan extension of the worms was induced by DR when bacteria density was 108cellsmL−1 and further dilutions would reduce the lifespan, which proposed a new dietary restriction regime in C. elegans. In addition, imaging analysis showed that DR regulated the subcellular localization DAF-16 in a way different from starvation that reduced lifespan of the worms. The platform allows not only horizontal studies of C. elegans in response to various environments over a wide range of concentrations, but also multiparameter evaluation of longevity in the worms with high temporal resolution, providing clues to better understand the aging process and help age-related drug screen.