Azelaic Acid Promotes Fatty Acid Desaturation in Caenorhabditis elegans at Cold Temperature, Thereby Enhancing Longevity

Abstract

Abstract Objectives Azelaic acid (AzA), a naturally occurring α, ω-dicarboxylic acid in wheat, rye, barley and sorghum, has been reported to exert anti-inflammatory and anti-oxidation property. AzA has long been used as an antiacne drug by inhibiting bacterial DNA synthesis. Recently, its role in reducing high fat diet-induced adiposity through activation of olfactory receptor 544 has been reported. However, its physiological role in environmental stress (e.g., fasting and cold) and aging is unknown. Methods We conducted PCR analysis and lifespan assay under multiple stress conditions (fasting, cold, and oxidative stress) using C. elegans Results Using C. elegans as an invertebrate animal model, we demonstrate that AzA treatment resulted in a significant extension of the survival under cold and oxidative stressed condition with no effects on the pumping rates, locomotive activities and growth rate. This was accompanied by a marked increase in expression of fatty acid desaturases genes, such as fat-1, fat-5 and fat-7, with a decrease in lipolysis related genes such as aak-2 and atgl-1. Moreover, the effect of AzA on the survival under cold condition was abolished in the fat-1, fat-5, fat-7 and aak-2 mutants. Conclusions Taken together, our results suggested that azelaic acid contributes to lifespan extension at low temperature in C. elegans through augmentation of unsaturated fatty acid synthesis. Funding Sources The Rural Development Administration of the Republic of Korea.