Probing the anti-aging role of polydatin in Caenorhabditis elegans on a chip

Abstract

C. elegans is widely used as a model organism in the study of aging and evaluation of anti-aging drugs due to its unique characteristics. In this work, we set out to investigate polydatin, a natural resveratrol glycoside, and its role in extending lifespan, improving oxidative stress resistance, and the possible regulation mechanism involved in the Insulin/IGF-1 signaling (IIS) pathway for the first time by using a flexible microfluidic device. The effects of polydatin on the lifespan, oxidative stress resistance, mobility and the expression of aging-related proteins and genes were explored. Polydatin was found to significantly extend the mean lifespan of worms by up to 30.7% and 62.1% under normal and acute stress conditions respectively. It improved the expression of the inducible oxidative stress protein (GST-4) and corresponding stroke frequencies in the transgenic CL2166 strain. Moreover, it also increased SOD-3::GFP expression in CF1553 worms and promoted DAF-16 nucleus translocation in TJ356 worms. The longevity-extending role of polydatin is partly attributed to its anti-oxidative activity and increased oxidative stress resistance by regulating the stress-resistance related proteins SOD-3, and daf-16 expression at protein and mRNA levels involved in the IIS pathway. The established microfluidic platform is capable of flexible operation with multiple functions, which not only supports the individual worm's long-term culture with sufficient nutrient exchange, but also facilitates mobility monitoring of the worm, immobilizing and imaging in a controllable and parallel manner. These interesting findings reported here highlight the significance of the natural compound polydatin in the study of aging-related diseases, and the utility of the microfluidic platform for applications in aging studies.