NIA Caenorhabditis Intervention Testing Program: identification of robust and reproducible pharmacological interventions that promote longevity across experimentally accessible, genetically diverse populations.

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.