Apiin Promotes Healthy Aging in <i>C. elegans</i> Through Nutritional Activation of DAF-16/FOXO, Enhancing Fatty Acid Catabolism and Oxidative Stress Resistance.

Apiin, a natural flavonoid sourced from parsley, demonstrates antioxidant properties; however, its specific anti-aging effects have yet to be investigated in <i>Caenorhabditis elegans</i> (<i>C. elegans</i>). This research utilized <i>C. elegans</i> models to examine the anti-aging effects of apiin and the underlying mechanisms. The findings indicated that 100 μg/mL apiin extended the mean lifespan of <i>C. elegans</i> by 26.70%. Furthermore, apiin improved age-related characteristics in <i>C. elegans</i>, such as reducing intestine lipofuscin accumulation and increasing head thrashes and body bends. Additionally, apiin significantly improved stress resistance under thermal, ultraviolet, and oxidative stress conditions. Transcriptomic analysis revealed that apiin induced the differential expression of genes related to fatty acid metabolism, lipid catabolism, and oxidoreductase activity in <i>C. elegans</i>. Metabolomic data further corroborated the modulation of fatty acid metabolic processes by apiin. Biochemical assays, including lipid staining, triglyceride quantification, and measurements of antioxidant enzyme activity, demonstrated a decrease in lipid content and an enhancement in antioxidant capacity in <i>C. elegans</i> treated with apiin. Moreover, apiin promoted the nuclear translocation of DAF-16 and upregulated key longevity-associated genes, including <i>sod-3</i>, <i>hsp-12.6</i>, <i>mtl-1</i>, and <i>ech-9</i>. These results indicate that apiin mitigates aging in <i>C. elegans</i> through mechanisms involving the activation of DAF-16 and the regulation of lipid metabolism and oxidative stress responses. Our findings underscore the potential of apiin as a natural therapeutic agent for aging and associated metabolic disorders.