The discovery of conserved genetic pathways whose manipulation via genetics and diet can lead to tremendous increases in lifespan, stress resistance, and prolonged health in a variety of different animals raises the prospect that pharmacological agents can be identified to achieve the same outcomes. A number of potential candidates have already been identified, but recent work in mice indicates that specific drug effects may be highly dependent on genetic background. The Caenorhabditis Intervention Testing Program (CITP) addresses this concern by creating a consortium of labs (based at the Buck Institute for Research on Aging, Rutgers University, and the University of Oregon) to systematically test a broad array of bioactive compounds for their effects on longevity and other biomarkers of aging across a broad set of nematode strains and species. Our collaborative research team has developed innovative approaches that allow a variety of high-throughput, high-precision assays of lifespan and healthspan.
Genetic Diversity
The CITP uses a diverse set of strains (from the three hermaphroditic Caenorhabditis species of C. elegans, C. briggsae, and C. tropicalis) obtained from the Caenorhabditis Genetics Center for our experiments. Strains from these species were chosen based on their large genetic diversity, geographic isolation, and ease of manipulation.
Reproducibility
A major focus of the CITP's work across the three labs has been creating reproducible data. Each lab follows the same Standardized Operating Procedures, utilizes the same equipment, and obtains the same lot numbers of reagents and compounds. Additionally, the same frozen stocks of nematodes originally obtained from the Caenorhabditis Genetics Center are shared amongst the three institutions.
Workflow
Once a compound has been selected for testing, a single CITP site performs the initial screen to determine levels of toxicity and efficacy. After determining the optimal dosage, all three labs then perform automated and manual lifespan as well as healthspan experiments in replicate.
Automated Lifespan Machine
To increase productivity, the CITP utilizes the C. elegans Lifespan Machine. Compared with manual assays, the use of multiple office scanners modified to hold petri plates containing nematodes, combined with hourly image capture and post-image processing, enables the automated, high-throughput collection of lifespan data with precise temporal resolution.
Healthspan
Our current efforts aim to identify increases in stress resistance and physical activity later in life that may be conferred by longevity-enhancing interventions. We are currently utilizing modified automated lifespan machines to perform a variety of healthspan assays, including oxidative and heat stress, and have employed software developed by our collaborators at Rutgers for quantifying worm movement (CeleST).
Compounds Tested to Date
Become a Collaborative Partner!
Although testing is performed by labs at the Buck Institute for Research on Aging, Rutgers University, and the University of Oregon, this project is designed to involve collaboration with other investigators. These prospective collaborators can be investigators from institutions, universities, or any other organization with ideas for interventions with the potential to promote healthy aging and extend lifespan.
We invite any interested researchers to recommend interventions they believe are worth testing. Each intervention suggested should include a rationale. This includes (but is not limited to):
- Previously published or unpublished work on the proposed intervention relating to health and/or lifespan
- Recommendation about the proper dose
- Suggested treatment protocol (i.e. solubility, sensitivities, etc.)
- Potential source for the material (i.e. vendor, cost, etc.)
If selected, the prospective collaborator will be asked to help analyze the collected data sets and participate in preparation of co-authored publications.
To propose an intervention, please visit the Submit page. For more information, visit our FAQs page.