Improvement Effect and Mechanism of Hydroxytyrosol on Skin Aging Induced Advanced Glycation End Products

<b>Objectives:</b> Skin aging, often accelerated by dietary advanced glycation end products (AGEs), poses both cosmetic and health challenges. This study explores the protective effects of hydroxytyrosol (HT), a potent antioxidant found in olives, against AGEs-induced skin aging in mice. <b>Methods:</b> A total of forty-eight 8-month-old specific pathogen-free (SPF) male C57BL/6J mice were randomly assigned to one of four groups: control, model, low-dose hydroxytyrosol (HT25), and high-dose hydroxytyrosol (HT50). An additional group of six 6-week-old SPF male C57BL/6J mice served as the youth group. The experimental period lasted 16 weeks. Following the intervention, skin, serum, and ileum samples were collected. <b>Results:</b> The results demonstrated that HT50 significantly increased skin moisture, epidermal thickness, and dermal thickness (<i>p</i> < 0.05). HT50 also significantly elevated hydroxyproline levels as well as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the skin while reducing malondialdehyde (MDA) content (<i>p</i> < 0.05). Furthermore, HT50 significantly reduced the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) (<i>p</i> < 0.05). Regarding intestinal integrity, hydroxytyrosol intervention (either HT25 or HT50) significantly increased the positive staining ratios of zonula occludens-1 (ZO-1) and occludin in the ileum (<i>p</i> < 0.05). <b>Conclusions:</b> HT improves skin hydration, thickness, and collagen levels while reducing oxidative stress and inflammation. Notably, HT also enhances intestinal barrier function, suggesting a role for the gut-skin axis. These findings highlight HT's potential as a natural intervention for skin aging.