Quinacrine and rimonabant prolong the life span of Caenorhabditis elegans.

Qin He, Shupan Guo, Aolan Zhou, Xin Gong, Wei Cheng, Haiyan Ren

Department of Pulmonary and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China. · pubmed

Paper

Abstract

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.

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Research summary

Quinacrine and rimonabant extend lifespan in C. elegans through modulation of the insulin/insulin-like growth factor pathway. This study investigates potential interventions that target the mechanisms of aging, aligning with the goal of understanding and addressing the root causes of aging rather than merely treating age-related symptoms.

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