Methyl 3,4-Dihydroxybenzoate Enhances Resistance to Oxidative Stressors and Lifespan in C. elegans Partially via daf-2/daf-16

Abstract

Genetic studies have elucidated mechanisms that regulate aging; however, there has been little progress in identifying drugs that retard ageing. <i>Caenorhabditis elegans</i> is among the classical model organisms in ageing research. Methyl 3,4-dihydroxybenzoate (MDHB) can prolong the life-span of <i>C. elegans</i>, but the underlying molecular mechanisms are not yet fully understood. Here, we report that MDHB prolongs the life-span of <i>C. elegans</i> and delays age-associated declines of physiological processes. Besides, MDHB can lengthen the life-span of <i>eat-2</i> (ad1113) mutations, revealing that MDHB does not work via caloric restriction (CR). Surprisingly, the life-span⁻extending activity of MDHB is completely abolished in <i>daf-2</i> (e1370) mutations, which suggests that <i>daf-2</i> is crucial for a MDHB-induced pro-longevity effect in <i>C. elegans</i>. Moreover, MDHB enhances the nuclear localization of <i>daf-16</i>/<i>FoxO</i>, and then modulates the expressions of genes that positively correlate with defenses against stress and longevity in <i>C. elegans</i>. Therefore, our results indicate that MDHB at least partially acts as a modulator of the <i>daf-2/daf-16</i> pathway to extend the lifespan of <i>C. elegans</i>, and MDHB might be a promising therapeutic agent for age-related diseases.