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Paroxetine promotes longevity via ser-7-dop-4-IIS axis in Caenorhabditis elegans

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Abstract

Paroxetine, a selective serotonin reuptake inhibitor, is widely used in the clinical treatment of depression. While several antidepressants show promise as geroprotectors, the role of paroxetine in aging remains unclear. In this study, we evaluated the lifespan extension effect of paroxetine in Caenorhabditis elegans (C. elegans) and elucidated the underlying mechanisms. The results showed that paroxetine can prolong lifespan concomitant extension of healthspan as indicated by increasing mobility and reducing lipofuscin accumulation, as well as confer protection to nematodes against different abiotic stresses. Paroxetine upregulated ser-7 expression and downregulated dop-4 expression. dop-4 RNA interference (RNAi) mimicked the beneficial effect of paroxetine on lifespan. Conversely, ser-7 RNAi abolished paroxetine-induced lifespan extension and the expression changes of dop-4 and genes related to insulin/insulin-like growth factor 1 signaling (IIS). Moreover, paroxetine exhibited a comparable lifespan extension effect to that observed in daf-2 or age-1 mutants; however, this effect was abolished in daf-16 mutant. Taken together, these results suggest that paroxetine promotes health and longevity in C. elegans through the ser-7-dop-4-IIS pathway, underscoring its potential as a geroprotector.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This study was supported by the National Natural Science Foundation of China (31871198), the Natural Science Foundation of Hunan Province (2022JJ30413), and the Scientific Research Fund of Hunan Provincial Education Department (23B0090).

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Author notes

  1. Yiming Zhou and Lijuan Chen contributed equally to this work.

Authors and Affiliations

  1. Center for Aging Biomedicine, College of Life Sciences, National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, Hunan Normal University, 36 Lushan Road, Changsha, 410081, Hunan, China

    Yiming Zhou, Lijuan Chen, Meijing Wang, Yang Yang, Bin Hu, Guolin Li & Fang Wei

  2. Key Laboratory of Hunan Province for Model Animal and Stem Cell Biology, School of Medicine, Hunan Normal University, Changsha, Hunan, China

    Guolin Li

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  1. Yiming Zhou
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Contributions

F.W. and G.L. designed research; Y.Z., L.C., M.W. and B.H. acquired the data; Y.Z., L.C., and Y.Y. analyzed data; Y.Z. and F.W. drafted the manuscript; F.W. and G.L. reviewed the manuscript. All authors read and approved the final manuscript.

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Correspondence to Fang Wei.

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Zhou, Y., Chen, L., Wang, M. et al. Paroxetine promotes longevity via ser-7-dop-4-IIS axis in Caenorhabditis elegans. GeroScience (2024). https://doi.org/10.1007/s11357-024-01492-7

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