REVIVE: a computational platform for systematically identifying rejuvenating chemical and genetic perturbations

Great efforts have been devoted to discovering rejuvenation strategies that counteract age-related functional decline and improve cellular functions in humans. However, new discoveries are currently driven by expert knowledge and require large amounts of resources. Here, we present REVIVE (Rejuvenation Estimation Via Insightful Virtual Experiments), the first computational framework for systematically predicting chemical and genetic perturbations that can restore a youthful transcriptional state based on gene expression data. REVIVE leverages age predictions to detect significant rejuvenating effects and quantifies the impact of perturbations on the hallmarks of aging. When applied to a large-scale <i>in silico</i> screen of more than 10000 compounds and genetic perturbations, REVIVE recapitulates known interventions as well as 477 novel compounds that restore a more youthful transcriptional state improving multiple aging hallmarks. Finally, we demonstrate the utility of REVIVE for repurposing perturbations to revert aged transcriptional states.