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Updated: May 16, 2025
A Simple Method for High Throughput Chemical Screening in Caenorhabditis Elegans
Published on: March 20, 2018
NIA Caenorhabditis Intervention Testing Program: identification of robust and reproducible pharmacological
Monica Driscoll1, Christine A Sedore2, Brian Onken3
1Rutgers, The State University of New Jersey, Piscataway, NJ, USA. driscoll@dls.rutgers.edu.
Abstract:
A core facet of the National Institute on Aging's mission is to identify pharmacological interventions that can promote human healthy aging and long life. As part of the comprehensive effort toward that goal, the NIA Division of Biology of Aging established the Caenorhabditis Intervention Testing Program (CITP) in 2013. The C. elegans model (with an ~ 21 day lifespan) has led the field in dissection of longevity genetics and offers features that allow for relatively rapid testing and for the potential elaboration of biological mechanisms engaged by candidate geroprotectants. CITP builds on this foundation by utilizing a genetically diverse set of intervention test strains so that "subjects" represent genetic diversity akin to that that between mouse and humans. Another distinctive aspect of the CITP is a dedicated focus on reproducibility of longevity outcomes as labs at three independent test sites confirm positive outcomes. The overall goal of the Caenorhabditis Intervention Testing Program (CITP) is to identify robust and reproducible pro-longevity interventions affecting genetically diverse cohorts in the Caenorhabditis genus. A strong Data Collection Center supports data collection and dissemination. Pharmacological interventions tested by CITP can be nominated by the general public, directed by in-house screens, or supported by published scientific literature. As of December 2024, CITP tested > 75 compounds and conducted > 725,000 animal assays over 891 trials. We identified 12 compounds that confer a ≥ 20% increase in median lifespan to reproducibly and robustly extend lifespan across multiple strains and labs. Five of these interventions have pro-longevity impact reported in the mouse literature (most CITP positive interventions are not tested yet in mouse). As part of the celebration of the 50th Anniversary of the NIA, we review the development history and accomplishments of the CITP program, and we comment on translation and the promise of advancing understanding of fundamental aging biology that includes the pharmacological intervention/health interface.
Insights
The Caenorhabditis Intervention Testing Program (CITP) identified 12 compounds that significantly extend lifespan in genetically diverse worms. These findings advance the search for pharmacological interventions promoting healthy aging.
Area of Science:
- Aging research
- Gerontology
- Pharmacology
Background:
- The National Institute on Aging (NIA) aims to identify interventions for healthy aging and longevity.
- The Caenorhabditis Intervention Testing Program (CITP) was established in 2013 to test compounds for their effects on lifespan.
- The nematode C. elegans is a model organism for aging research due to its short lifespan and genetic tractability.
Purpose of the Study:
- To identify robust and reproducible pro-longevity interventions.
- To test pharmacological compounds for their ability to extend lifespan in genetically diverse C. elegans.
- To advance the understanding of aging biology and pharmacological intervention interfaces.
Main Methods:
- Utilized a genetically diverse set of C. elegans strains across three independent test sites.
- Conducted over 725,000 animal assays across 891 trials, testing more than 75 compounds.
- Focused on reproducibility of longevity outcomes and data dissemination through a Data Collection Center.
Main Results:
- Identified 12 compounds that reproducibly increase median lifespan by at least 20% across multiple strains and labs.
- Five of these pro-longevity interventions have reported effects in mouse models.
- The program has generated extensive data on compound efficacy and reproducibility.
Conclusions:
- The CITP has successfully identified multiple compounds that robustly extend lifespan in C. elegans.
- These findings contribute to the NIA's mission of promoting healthy aging through pharmacological interventions.
- The program's approach emphasizes genetic diversity and reproducibility, offering a strong foundation for future aging research.
