Sustainable Ellagitannin-Rich Pomegranate Peel Extracts Activate SKN-1/NRF2-Dependent Antioxidant Responses and Promote Healthy Aging in Caenorhabditis elegans

The valorization of food by-products represents a key strategy for sustainable food systems and the circular bioeconomy. Pomegranate peels from two selected Italian cultivars were subjected to environmentally friendly extraction processes aimed at optimizing ellagitannins’ recovery and exploiting their biological activity. Punicalagin (PU) was the predominant compound, and the extracts exhibited high antioxidant capacity in both DPPH and FRAP assays. The Granato cultivar was selected for in vivo evaluation on the Caenorhabditis elegans (C. elegans) nematode model, where it extended lifespan and improved key healthspan markers. Locomotion, feeding activity, muscle integrity, and intestinal barrier function were improved through the activation of conserved stress-response pathways, particularly the SKN-1/NRF2 axis. The results were associated with improved mitochondrial function and reduced age-related oxidative stress, consistent with a hormetic mechanism. The extract also exhibited antibacterial activity, mainly against Gram-positive bacteria. Overall, the results highlight pomegranate peel as a sustainable source of high-value bioactive compounds with potential applications in nutrition, dietary supplements, and dermo-cosmetics.