Related Experiment Video
Updated: May 6, 2026
A Simple Method for High Throughput Chemical Screening in Caenorhabditis Elegans
Published on: March 20, 2018
A pharmacological network for lifespan extension in Caenorhabditis elegans
Xiaolan Ye1, James M Linton, Nicholas J Schork
1Division of Basic Sciences, Fred Hutchison Cancer Research Center, Howard Hughes Medical Institute, Seattle, WA, USA.
Abstract:
One goal of aging research is to find drugs that delay the onset of age-associated disease. Studies in invertebrates, particularly Caenorhabditis elegans, have uncovered numerous genes involved in aging, many conserved in mammals. However, which of these encode proteins suitable for drug targeting is unknown. To investigate this question, we screened a library of compounds with known mammalian pharmacology for compounds that increase C. elegans lifespan. We identified 60 compounds that increase longevity in C. elegans, 33 of which also increased resistance to oxidative stress. Many of these compounds are drugs approved for human use. Enhanced resistance to oxidative stress was associated primarily with compounds that target receptors for biogenic amines, such as dopamine or serotonin. A pharmacological network constructed with these data reveal that lifespan extension and increased stress resistance cluster together in a few pharmacological classes, most involved in intercellular signaling. These studies identify compounds that can now be explored for beneficial effects on aging in mammals, as well as tools that can be used to further investigate the mechanisms underlying aging in C. elegans.
Insights
Researchers screened drugs for their ability to extend lifespan and improve stress resistance in C. elegans. Many existing human drugs showed benefits, particularly those targeting biogenic amine receptors, offering potential for aging research.
Area of Science:
- Gerontology
- Pharmacology
- Molecular Biology
Background:
- Aging research aims to identify drugs delaying age-associated diseases.
- Numerous aging-related genes in C. elegans are conserved in mammals, but drug targets remain unclear.
Purpose of the Study:
- To screen pharmacologically active compounds for lifespan extension in C. elegans.
- To identify potential drug targets for modulating aging and stress resistance.
Main Methods:
- Screened a library of compounds with known mammalian pharmacology for lifespan-extending effects in C. elegans.
- Assessed compounds for increased resistance to oxidative stress.
- Constructed a pharmacological network to analyze relationships between compounds, lifespan, and stress resistance.
Main Results:
- Identified 60 compounds that increase C. elegans lifespan.
- 33 of these compounds also enhanced resistance to oxidative stress.
- Compounds targeting biogenic amine receptors (dopamine, serotonin) were strongly associated with improved stress resistance.
- Lifespan extension and stress resistance clustered within specific pharmacological classes, primarily involved in intercellular signaling.
Conclusions:
- Identified existing human drugs that extend lifespan and enhance stress resistance in C. elegans.
- These compounds represent potential candidates for further investigation in mammalian aging.
- The study provides tools to explore the molecular mechanisms of aging and drug action in C. elegans.
