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Updated: Jun 20, 2026
A Simple Method for High Throughput Chemical Screening in Caenorhabditis Elegans
Published on: March 20, 2018
A high-throughput screen for chemicals that increase the lifespan of Caenorhabditis elegans
Michael Petrascheck1, Xiaolan Ye, Linda B Buck
1Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Abstract:
One long-term goal of aging research is to find drugs that can delay aging and the onset of age-associated diseases. With this in mind, we screened 88,000 chemicals for the ability to increase the lifespan of Caenorhabditis elegans nematodes. We found that mianserin, a serotonin receptor antagonist used as an antidepressant in humans, can increase C. elegans lifespan when given only during adulthood. This effect is reduced or abolished by mutations that affect serotonin synthesis or serotonin reuptake at synapses. It also requires a serotonin receptor and an octopamine receptor, both of which are inhibited by the drug. Mianserin has no effect on the lifespan of animals with increased longevity due to dietary restriction or with a mutation that reduces food intake, indicating that the drug extends lifespan via mechanisms linked to dietary restriction. These studies indicate that lifespan can be increased by inhibiting certain kinds of neurotransmission previously implicated in food sensing, possibly by mimicking a physiological state associated with dietary restriction.
Insights
Researchers screened 88,000 chemicals and found mianserin, an antidepressant, extends nematode lifespan. This drug works by inhibiting neurotransmission linked to food sensing, potentially mimicking dietary restriction effects.
Area of Science:
- Aging research
- Neuroscience
- Pharmacology
Background:
- A key goal in aging research is identifying interventions to delay aging and age-related diseases.
- Screening chemical compounds is a common strategy to discover novel longevity-promoting drugs.
Purpose of the Study:
- To screen a large chemical library for compounds that extend lifespan in the nematode model organism Caenorhabditis elegans.
- To investigate the mechanism by which identified lifespan-extending compounds exert their effects.
Main Methods:
- A large-scale chemical screen of 88,000 compounds was performed using C. elegans to identify lifespan extenders.
- Genetic analysis involving mutations affecting serotonin pathways and receptor function was used to dissect the mechanism of action.
- Comparative studies were conducted with animals exhibiting increased longevity through dietary restriction or reduced food intake.
Main Results:
- Mianserin, a serotonin receptor antagonist used in humans, was identified as a lifespan-extending compound in adult C. elegans.
- The lifespan-extending effect of mianserin was dependent on serotonin synthesis, reuptake, a specific serotonin receptor, and an octopamine receptor.
- Mianserin's effect on lifespan was independent of mechanisms related to dietary restriction or reduced food intake.
Conclusions:
- Inhibiting specific neurotransmission pathways, particularly those involved in food sensing, can extend lifespan.
- The findings suggest that mianserin may extend lifespan by mimicking a physiological state associated with dietary restriction.
- This study highlights the potential of targeting neurotransmission for developing interventions against aging and age-associated diseases.
