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

中文翻译：

---

3,4-二羟基苯甲酸甲酯可部分通过daf-2 / daf-16增强秀丽隐杆线虫对氧化应激的抗性和寿命

遗传研究阐明了调节衰老的机制。然而，在鉴定延缓衰老的药物方面进展甚微。秀丽隐杆线虫是衰老研究中的经典模型生物之一。3,4-二羟基苯甲酸甲酯（MDHB）可以延长秀丽隐杆线虫的寿命，但其潜在的分子机理尚未完全明了。在这里，我们报告MDHB延长线虫的寿命，并延迟与年龄相关的生理过程的下降。此外，MDHB可以延长eat-2（ad1113）突变的寿命，这表明MDHB无法通过热量限制（CR）起作用。令人惊讶的是，daf-2（e1370）突变完全消除了MDHB的寿命延长活性，这表明daf-2对于秀丽隐杆线虫中MDHB诱导的长寿效应至关重要。而且，MDHB增强daf-16 / FoxO的核定位，然后调节与秀丽隐杆线虫对抗压力和寿命的防御作用正相关的基因表达。因此，我们的结果表明，MDHB至少部分充当daf-2 / daf-16途径的调节剂，以延长秀丽隐杆线虫的寿命，并且MDHB可能是有前途的与年龄有关的疾病的治疗剂。