Quinacrine and rimonabant prolong the life span of Caenorhabditis elegans.

Aging and age-related disorders are significant global health concerns, driving interest in potential preventative strategies. In this study, we established a high-throughput screening system to reveal the effects of quinacrine and rimonabant on lifespan extension in C. elegans. Mechanistically, quinacrine influences the metabolic and immune pathways through the insulin/insulin-like growth factor (IIS) pathway, as it fails to prolong longevity in IIS pathway mutants while boosting the expression of the downstream gene sod-3. Metabolomic profiling revealed a significant elevation of phosphatidylserine in quinacrine-treated worms. Parallel investigations showed that rimonabant exerts its lifespan-extending effects via the IIS pathway, specifically through the DAF-2/HSF-1 regulatory axis. It promotes longevity of C. elegans by enhancing antioxidant defense and detoxification pathways. Our findings position both quinacrine and rimonabant as promising anti-aging candidates, offering novel mechanistic insights for developing interventions against age-related disorders.