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<p>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 <i>C. elegans</i>. 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 <i>sod-3</i>. 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 <i>C. elegans</i> 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.</p>

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Quinacrine and rimonabant prolong the life span of Caenorhabditis elegans

  • 期刊论文

  • 发表日期：

    2025年6月25日

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

摘要

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.