Serotonin receptors antagonistically modulate Caenorhabditis elegans longevity.
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.
Murakami
Hana
H
Gheens Center on Aging, Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40202, USA. shin.murakami@louisville.edu
Murakami
Shin
S
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology*; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008136:Longevity / Q000235:genetics / Q000502:physiology; D009154:Mutation; D034622:RNA Interference; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
D043562:Receptors, G-Protein-Coupled; D011985:Receptors, Serotonin; D012701:Serotonin; D007334:Insulin-Like Growth Factor I