Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, China.
School of Nursing, Guangdong Pharmaceutical University, Guangzhou 510632, China.
Int J Mol Sci. 2018 Jun 5;19(6):1670. doi: 10.3390/ijms19061670.
Genetic studies have elucidated mechanisms that regulate aging; however, there has been little progress in identifying drugs that retard ageing. is among the classical model organisms in ageing research. Methyl 3,4-dihydroxybenzoate (MDHB) can prolong the life-span of , but the underlying molecular mechanisms are not yet fully understood. Here, we report that MDHB prolongs the life-span of and delays age-associated declines of physiological processes. Besides, MDHB can lengthen the life-span of (ad1113) mutations, revealing that MDHB does not work via caloric restriction (CR). Surprisingly, the life-span⁻extending activity of MDHB is completely abolished in (e1370) mutations, which suggests that is crucial for a MDHB-induced pro-longevity effect in . Moreover, MDHB enhances the nuclear localization of /, and then modulates the expressions of genes that positively correlate with defenses against stress and longevity in . Therefore, our results indicate that MDHB at least partially acts as a modulator of the pathway to extend the lifespan of , and MDHB might be a promising therapeutic agent for age-related diseases.
遗传研究已经阐明了调节衰老的机制；然而，在鉴定能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式生物之一。3,4-二羟基苯甲酸甲酯（MDHB）可以延长秀丽隐杆线虫的寿命，但潜在的分子机制尚不完全清楚。在这里，我们报告 MDHB 可以延长秀丽隐杆线虫的寿命并延缓与年龄相关的生理过程的下降。此外，MDHB 可以延长 （ad1113）突变体的寿命，这表明 MDHB 不是通过限制热量摄入（CR）起作用的。令人惊讶的是，MDHB 的寿命延长活性在 （e1370）突变体中完全被废除，这表明在 MDHB 诱导的长寿效应中 是至关重要的。此外，MDHB 增强了 / 的核定位，然后调节与应激和长寿正相关的基因的表达在秀丽隐杆线虫中。因此，我们的结果表明，MDHB 至少部分作为 的途径的调节剂来延长秀丽隐杆线虫的寿命，并且 MDHB 可能是治疗与年龄相关的疾病的有前途的治疗剂。
