Effects of Finasteride exposure on lifespan and locomotor phenotypes

Finasteride is one of the core medications for treating androgen-associated diseases in men. It exhibits multiple therapeutic functions, including inhibiting 5α-reductase, reducing dihydrotestosterone levels, and improving conditions, including prostate enlargement and hair loss. Using Drosophila as the primary model and a mouse behavioral assay as a complementary approach, we combined developmental and behavioral assessments, morphological analyses of motor and sensory neurons, transcriptomics, and genetic methods to investigate developmental, neuronal, and behavioral changes associated with Finasteride exposure and explore their potential molecular basis. Our results indicate that Finasteride exposure is associated with increased intestinal reactive oxygen species (ROS) accumulation and shortened lifespan in both sexes, together with significantly reduced starvation resistance in males. In addition, Finasteride exposure was also associated with altered neuromuscular junction (NMJ) morphology, reduced locomotor performance, and decreased cask expression. Motor-neuron CASK overexpression improved NMJ morphology and locomotor performance in Finasteride-exposed flies. Overall, this study reveals changes in lifespan and locomotor phenotypes associated with Finasteride exposure and further highlights the importance of investigating its broader biological effects in other experimental systems.