The effects of paroxetine on lifespan, feeding behavior, and other physiological parameters in the nematode C....

Paroxetine, a widely prescribed selective serotonin reuptake inhibitor (SSRI), is known for its metabolic side effects, yet its long-term physiological impacts remain incompletely understood. This study investigated the effects of paroxetine on lifespan, feeding behavior, and fat accumulation in Caenorhabditis elegans across different developmental stages and dietary conditions. We found that low-dose paroxetine extended lifespan when exposure began early, while high doses consistently reduced lifespan. Notably, the lifespan-extending effects appeared to be diminished when worms were fed a high-glucose diet, suggesting that dietary context may influence the physiological outcomes of paroxetine. Paroxetine also increased food intake without causing fat accumulation, indicating a possible metabolic uncoupling. These effects were independent of major serotonergic, dopaminergic, and insulin-like signaling pathways, pointing to alternative mechanisms. Overall, our findings highlight the potential roles of dose, timing of exposure, and diet in shaping the physiological impacts of SSRIs.