Serotonin receptors antagonistically modulate Caenorhabditis elegans longevity

Aging Cell. 2007 Aug;6(4):483-8. doi: 10.1111/j.1474-9726.2007.00303.x. Epub 2007 Jun 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / physiology*
  • Gene Expression Regulation
  • Insulin-Like Growth Factor I / metabolism
  • Longevity* / genetics
  • Longevity* / physiology
  • Mutation
  • RNA Interference
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / metabolism*
  • Serotonin / metabolism*

Substances

  • Receptors, G-Protein-Coupled
  • Receptors, Serotonin
  • Serotonin
  • Insulin-Like Growth Factor I