Quinacrine and rimonabant prolong the life span of Caenorhabditis elegans

被引：0
作者：
He, Qin [1 ,2 ]
Guo, Shupan [1 ,2 ]
Zhou, Aolan [1 ,2 ]
Gong, Xin [1 ,2 ]
Cheng, Wei [1 ,2 ,3 ]
Ren, Haiyan [1 ,2 ,3 ]
机构：
[1] Sichuan Univ, Resp Infect & Intervent Lab Frontiers Sci Ctr Dis, Dept Pulm & Crit Care Med, West China Hosp, Chengdu 610041, Sichuan, Peoples R China
[2] Sichuan Univ, State Key Lab Biotherapy, West China Hosp, Chengdu 610041, Sichuan, Peoples R China
[3] Sichuan Univ, Collaborat Innovat Ctr Biotherapy, West China Hosp, Chengdu 610041, Peoples R China
来源：
GEROSCIENCE | 2025年
基金：
中国国家自然科学基金;
关键词：
Oxidative stress; Inflammation; Metabolism; Aging; IIS pathway; SUBJECTIVE MEMORY COMPLAINTS; OXIDATIVE STRESS; PHOSPHATIDYLSERINE; EXPRESSION; EFFICACY; MODELS; RISK; AGE;
D O I：
10.1007/s11357-025-01729-z
中图分类号：
R592 [老年病学]; C [社会科学总论];
学科分类号：
03 ; 0303 ; 100203 ;
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.
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页数：14
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