A cross-species drug-discovery platform to accelerate the identification of lifespan-extending interventions.

Abstract

We develop an integrated, high-throughput platform to evaluate pharmacological lifespan-extending interventions across five model organisms spanning unicellular to mammalian biology including yeast, nematodes, fruit flies, killifish, and mice. By combining automated imaging, miniaturized assays, and deep-learning-based death detection, we evaluate over 400 compounds across thousands of conditions. In S. cerevisiae, a miniaturized PI/flow cytometry CLS assay enables scalable screening and identifies key assay confounders, while in C. elegans and D. melanogaster, compact imaging platforms coupled to YOLO-based detection provide a no-transfer, high-throughput survival scoring, and capture compound-, diet-, and sex-dependent effects. In killifish, we develop an in-house drug-pellet formulation for standardized oral delivery in large cohorts, and in mice we combine longitudinal lifespan studies with home-cage activity monitoring to assess late-life interventions. Cross-species integration identifies multi-species geroprotectors and reveals convergence on known and novel conserved longevity pathways, illustrating how this scalable framework can prioritize interventions with high translational potential.