I have no ability to read the whole paper but here is the abstract. The authors do not use the name PBT2 but clioquinol.

Free Radic Biol Med

. 2025 Jun 24:S0891-5849(25)00795-6.

doi: 10.1016/j.freeradbiomed.2025.06.046. Online ahead of print.

Deciphering the Anti-senescent Effects of Clioquinol: Lifespan Prolongation, Metabolic Homeostasis, and Phenotypic Rehabilitation in Drosophila melanogaster

Xiao-Meng Liu ¹, Xu-Dong Liu ², Yu-Qi Zhang ³, Yu-Tong Liu ⁴, Lu-Wei Lv ⁵, Meng-Hao Wang ³, Qin Ren ³, Yang Liu ⁶, Meng-Zhen Wu ⁶, Ying-Xin Shi ⁶, Yun-Xia Zhang ⁷, Bing Li ⁸

Affiliations Expand

• PMID: 40570982

DOI: 10.1016/j.freeradbiomed.2025.06.046

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a halogenated 8-hydroxyquinoline, was once an oral antiparasitic for intestinal amoebiasis in the 1950s-1970s but was withdrawn due to neurotoxicity.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.

Keywords: Alzheimer's disease; Clioquinol; Drosophila melanogaster; Healthy lifespan; Intestinal homeostasis; mechanism.