Deciphering the anti-senescent effects of Clioquinol: Lifespan prolongation, metabolic homeostasis, and phenotypic rehabilitation in Drosophila melanogaster.

Xiao-Meng Liu, Xu-Dong Liu, Yu-Qi Zhang, Yu-Tong Liu, Lu-Wei Lv, Meng-Hao Wang, Qin Ren, Yang Liu, Meng-Zhen Wu, Ying-Xin Shi, Yun-Xia Zhang, Bing Li

Department of Nutrition and Food Hygiene, College of Public Health, Xinxiang Medical University, Xinxiang, 453003, Henan, China; Institute of Translational Medicine, College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou, 466001, Henan, China. Electronic address: [email protected] of Nutrition and Food Hygiene, College of Public Health, Xinxiang Medical University, Xinxiang, 453003, Henan, China; Institute of Translational Medicine, College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou, 466001, Henan, China. Electronic address: [email protected]. · pubmed

Paper

Abstract

Clioquinol (CQ), a halogenated 8-hydroxyquinoline, was once an oral antiparasitic for intestinal amoebiasis in the 1950s-1970s but was withdrawn due to neurotoxicity. Lately, it shows activities beyond antimicrobials, like in osteoarthritis and neurodegenerative diseases, yet its anti-aging effects are unclear. This study used Drosophila melanogaster to test CQ's effects on healthy aging and age-related diseases. Results showed CQ extended lifespan in normal or high-fat diet flies, enhanced stress resistance and glycolipid metabolism, improved motility, and prevented intestinal inflammation and obesity, and alleviated age-related digestive decline. In addition, CQ also prolonged lifespan and improved motor activity in Alzheimer's flies. Gene-deficient lifespan experiments and transcriptomic analysis revealed CQ's anti-aging mechanisms involving multiple signaling pathways, such as differential gene expression in HIF-1 signaling, Notch signaling, P53 signaling, JAK-STAT signaling, FOXO signaling, and IL-17 signaling pathway, activated TNF signaling and PI3K-Akt signaling pathway, and inhibited mTOR signaling pathway. Overall, CQ shows promise as a candidate for anti-aging interventions and treating aging-related diseases.

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Research summary

Clioquinol extends lifespan and improves healthspan in Drosophila melanogaster through multiple signaling pathways. The study addresses mechanisms of aging and potential interventions, making it relevant to longevity research.

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