• Open Access

Serotonin receptors antagonistically modulate Caenorhabditis elegans longevity

Authors

  • Hana Murakami,

    1. Gheens Center on Aging, Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY, USA
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  • Shin Murakami

    1. Gheens Center on Aging, Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY, USA
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Shin Murakami, Gheens Center on Aging, Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, 580 S Preston Street, BaxterII, RM102, Louisville, KY 40202, USA. Tel.: 502-852-2554; fax: 502-852-2660; e-mail: shin.murakami@louisville.edu

Summary

The neurotransmitter serotonin has been implicated in affecting the variation of longevity in natural Drosophila populations and age-related diseases in mammals. Based on these observations, it has been predicted that serotonin signal, perhaps at levels of serotonin biosynthesis, may control lifespan. Here, we investigated a variety of mutations in serotonin-signal genes, including serotonin biosynthesis genes, a serotonin transporter gene, and serotonin receptor genes. Despite this prediction, mutations in the serotonin biosynthesis genes had little or modest effects on lifespan, while the mod-5 mutation with increased availability of serotonin caused a modest life-shortening effect. In contrast, a deletion mutation of the ser-1 serotonin receptor gene increased longevity by up to 46%, likely through the insulin/insulin-like growth factor 1 pathway. This result suggests an interaction between the serotonin pathway and the insulin/insulin-like growth factor 1 pathway. A deletion mutation of another serotonin receptor gene, ser-4, shortened early to mid lifespan. The results suggest that serotonin signal antagonistically modulates longevity through different serotonin receptors. This study may indicate serotonin receptors as a potential target for antigeric interventions.

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