Green-Extracted <i>Ficus carica</i> L. Fruit Polysaccharides Promote Longevity in <i>Caenorhabditis elegans</i> via Modulation of SKN-1 and IIS Pathway.

In this study, polysaccharides from <i>Ficus carica</i> L. fruits (FCPs) were extracted using a deep eutectic solvent (DES)-based ultrasound-assisted extraction (UAE) method. The physicochemical properties of the FCPs were then characterized, and the anti-aging effects of FCPs were evaluated in <i>Caenorhabditis elegans</i> (<i>C. elegans</i>). It was demonstrated that FCPs significantly extended the lifespan of the nematodes, while improving locomotor activity without affecting the body size or reproductive capacity. Meanwhile, FCPs reduced lipofuscin accumulation, decreased intracellular reactive oxygen species (ROS) levels, and increased the survival of <i>C. elegans</i> under oxidative stress. Moreover, FCPs upregulated the expression of antioxidant genes <i>sod-1</i>, <i>sod-3</i>, <i>ctl-2</i>, <i>ctl-3</i> and <i>gst-4</i>. The expression of <i>skinhead-1</i> (<i>skn-1</i>), a homologue gene of mammalian <i>nuclear factor erythroid 2-related factor</i> (<i>Nrf</i>) in <i>C. elegans</i>, was also elevated upon FCPs treatment. Knockdown of <i>skn-1</i> expression by RNA interference abolished the lifespan extension and ROS reduction in FCPs-treated <i>C. elegans</i>, indicating that the SKN-1-mediated signaling was essential for the anti-aging effects of FCPs. Additionally, FCPs caused downregulation of the key components of the insulin/IGF-1 signaling (IIS) pathway, <i>age-1</i>, <i>akt-1</i>, and <i>akt-2</i>. Overall, these results suggested that FCPs promoted longevity in <i>C. elegans</i> via modulation of SKN-1 and IIS pathway.