Effects of European Bilberry Extract on Skin Aging Associated with Consumption of a High Temperature Roasted Diet in Rats

Background/Objectives: Skin aging is accompanied by increased protein glycation in the skin, suggesting a potential link between dietary advanced glycation end products (AGEs) and skin aging. European bilberry extract (EBE), rich in anthocyanins, has shown potential in reducing AGEs; however, its protective effects against AGE-induced skin aging and the underlying mechanisms remain unclear. We aimed to investigate the association between roasted high-AGE diet exposure and skin aging, and to evaluate the protective effects of EBE and its potential mechanisms. Methods: A long-term roasted high-AGE diet exposure model was established in rats using a roasted high-AGE diet. Rats received EBE (100 mg/kg/day) or vehicle by oral gavage for 16 months. AGE levels were quantified by UHPLC-MS/MS. Skin aging phenotypes were assessed by histomorphometry and senescence-related biomarkers. Lipidomics analysis was performed to evaluate alterations in skin lipid profiles and the effects of EBE. Results: In rats, high-AGE feeding increased circulating and skin-deposited AGEs, reduced epidermal and stratum corneum thickness, and elevated senescence markers. Lipidomics revealed significant lipid remodeling, including decreased unsaturated fatty acids and glycerolipids; these lipid alterations were consistent with changes in lipid pathways related to barrier integrity, energy storage, and inflammatory signaling. EBE supplementation reduced systemic and cutaneous AGE accumulation, improved skin structure, attenuated senescence, and partially restored lipid homeostasis, including lipids associated with barrier function, energy storage, and inflammation. Conclusions: A roasted high-AGE diet is associated with and may accelerate skin aging, accompanied by lipid metabolism disruption and activation of inflammation-related pathways. EBE alleviates roasted high-AGE diet-induced skin aging and barrier-related molecule disruption, along with restoring lipid homeostasis and suppressing pro-inflammatory responses.