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Published on: March 20, 2018
Sertraline Promotes Health and Longevity in Caenorhabditis elegans
Yu Liang1, Yiming Zhou1, Can Zhou1
1Center for Aging Biomedicine, National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.
Introduction:
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.
Methods:
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.
Results:
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.
Conclusion:
Sertraline promotes health and longevity in C. elegans through ser-7-insulin/AMPK pathways.
