Abstract：
While several antidepressants have been identified as potential geroprotectors, the effect and mechanism of sertraline on healthspan remain to be elucidated. Here, we explored the role of sertraline in the lifespan and healthspan of Caenorhabditis elegans.
The optimal effect concentration of sertraline was first screened in wild-type N2 worms under heat stress conditions. Then, we examined the effects of sertraline on lifespan, reproduction, lipofuscin accumulation, mobility, and stress resistance. Finally, the expression of serotonin signaling and aging-related genes was investigated to explore the underlying mechanism, and the lifespan assays were performed in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants.
Sertraline extended the lifespan in C. elegans with concomitant extension of healthspan as indicated by increasing mobility and reducing fertility and lipofuscin accumulation, as well as enhanced resistance to different abiotic stresses. Mechanistically, ser-7 orchestrated sertraline-induced longevity via the regulation of insulin and AMPK pathways, and sertraline-induced lifespan extension in nematodes was abolished in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants.
Sertraline promotes health and longevity in C. elegans through ser-7-insulin/AMPK pathways.
The optimal effect concentration of sertraline was first screened in wild-type N2 worms under heat stress conditions. Then, we examined the effects of sertraline on lifespan, reproduction, lipofuscin accumulation, mobility, and stress resistance. Finally, the expression of serotonin signaling and aging-related genes was investigated to explore the underlying mechanism, and the lifespan assays were performed in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants.
Sertraline extended the lifespan in C. elegans with concomitant extension of healthspan as indicated by increasing mobility and reducing fertility and lipofuscin accumulation, as well as enhanced resistance to different abiotic stresses. Mechanistically, ser-7 orchestrated sertraline-induced longevity via the regulation of insulin and AMPK pathways, and sertraline-induced lifespan extension in nematodes was abolished in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants.
Sertraline promotes health and longevity in C. elegans through ser-7-insulin/AMPK pathways.
摘要：
背景：虽然几种抗抑郁药已被确定为潜在的老年保护剂，舍曲林对健康的影响和机制仍有待阐明。这里,我们探讨了舍曲林在秀丽隐杆线虫的寿命和健康中的作用(C.线虫）。
方法：首先在热胁迫条件下在野生型N2蠕虫中筛选舍曲林的最佳作用浓度。然后，我们研究了舍曲林对寿命的影响，繁殖，脂褐素积累，移动性,和抗压力。最后,研究了5-HT信号和衰老相关基因的表达，以探索潜在的机制，寿命测定在ser-7RNAi菌株中进行，daf-2、daf-16和aak-2突变体。
结果：舍曲林延长了秀丽隐杆线虫的寿命，并伴随着健康跨度的延长，这通过增加活动性和减少生育能力和脂褐素积累来表明，以及增强对不同非生物胁迫的抗性。机械上,ser-7通过调节胰岛素和AMPK途径协调舍曲林诱导的寿命，在ser-7RNAi菌株中，舍曲林诱导的线虫寿命延长被废除，daf-2、daf-16和aak-2突变体。
结论：舍曲林通过ser-7-胰岛素/AMPK途径促进秀丽隐杆线虫的健康和长寿。
方法：首先在热胁迫条件下在野生型N2蠕虫中筛选舍曲林的最佳作用浓度。然后，我们研究了舍曲林对寿命的影响，繁殖，脂褐素积累，移动性,和抗压力。最后,研究了5-HT信号和衰老相关基因的表达，以探索潜在的机制，寿命测定在ser-7RNAi菌株中进行，daf-2、daf-16和aak-2突变体。
结果：舍曲林延长了秀丽隐杆线虫的寿命，并伴随着健康跨度的延长，这通过增加活动性和减少生育能力和脂褐素积累来表明，以及增强对不同非生物胁迫的抗性。机械上,ser-7通过调节胰岛素和AMPK途径协调舍曲林诱导的寿命，在ser-7RNAi菌株中，舍曲林诱导的线虫寿命延长被废除，daf-2、daf-16和aak-2突变体。
结论：舍曲林通过ser-7-胰岛素/AMPK途径促进秀丽隐杆线虫的健康和长寿。
