秀丽隐杆线虫
舍曲林
生物
长寿
突变体
RNA干扰
药理学
细胞生物学
基因
遗传学
内分泌学
抗抑郁药
海马体
核糖核酸
作者
Yu Liang,Yiming Zhou,Can Zhou,Xin Cai,Li Liu,Fang Wei,Guolin Li
出处
期刊:Gerontology
[S. Karger AG]
日期:2024-01-01
卷期号:70 (4): 408-417
摘要
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.
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