Paramylon isolated from Euglena gracilis EOD-1 extends lifespan through activation of DAF-16-mediated antioxidant pathway via clec-196 in Caenorhabditis elegans

Paramylon (PM), an insoluble β-1,3-glucan produced by Euglena gracilis, reportedly possesses immunomodulatory and metabolic regulatory effects. However, its effect on longevity remains unclear. For this study, using Caenorhabditis elegans as a model, we evaluated lifespan-extending effects of PM and elucidated its underlying molecular mechanisms. Dietary PM supplementation prolonged the C. elegans lifespan significantly without affecting either growth or fertility, indicating the effects as independent of caloric restriction. Findings indicate that PM intake strongly upregulated clec-196, an ortholog of the β-glucan receptor DECTIN-1. Also, RNA interference of clec-196 eliminated PM-induced lifespan extension, indicating clec-196 as necessary for the physiological response to PM. Moreover, PM supplementation increased expression of jnk-1 and daf-16, which were suppressed when clec-196 was knocked down, suggesting that clec-196 functions upstream of the JNK-1/DAF-16 pathway. The lifespan-extending effect of PM was completely absent in loss-of-function mutant of daf-16, underscoring its indispensable role. Furthermore, PM feeding activated the DAF-16-mediated antioxidant pathway, as evidenced by upregulation of antioxidant genes and by suppression of hydrogen peroxide accumulation. These findings suggest that PM might serve as a functional food ingredient exhibiting anti-aging potential.