Objective To observe the effect of intermittent fasting on D⁃galactose⁃induced skin aging in aging mice. Methods Eighteen SPF⁃grade male C57BL/6 mice were selected and randomly divided into blank group, D⁃galactose model group, or intermittent fasting group, with 6 mice in each group. Except for the blank group, the remaining two groups received intraperitoneal injections of D⁃galactose to establish an aging mouse model. Simultaneously with modeling, the intermittent fasting group was subjected to intermittent fasting intervention, while the remaining two groups received a normal diet. The intervention lasted for 12 weeks. During the intervention, the physiological and skin conditions of the mice in each group were observed, and body weight was measured regularly. After 12 weeks of intervention, the mice were killed. HE staining and collagen fiber and elastic fiber staining kit (EVG⁃Weigert) were used to observe morphological changes in the mouse skin. The contents of superoxide dismutase (SOD), malondialdehyde (MDA), and hydroxyproline (HYP) in skin tissue and serum were detected. Results As the intervention progressed, the D⁃galactose model group demonstrated obvious signs of aging, while the intermittent fasting group exhibited improvements in various physiological states and skin aging manifestations compared to the D⁃galactose model group. Body weight changes in the D⁃galactose model group were largely consistent with the blank group, while the intermittent fasting group exhibited significantly lower body weight than the remaining two groups. Compared with the blank group, the epidermis and dermis thickness were thinner, and the elastic fiber area was reduced in the skin of the D⁃galactose model group (P<0.05). Compared with the D⁃galactose model group, the intermittent fasting group showed thicker epidermis and dermis and an increased elastic fiber area (P<0.05). Compared with the blank group, the contents of SOD and HYP in both skin tissue and serum were reduced, while serum MDA content elevated in the D⁃galactose model group (P<0.05). Compared with the D⁃galactose model group, the intermittent fasting group yielded elevated serum SOD and HYP contents, whereas lower MDA contents in both skin tissue and serum (P<0.05). Conclusion Intermittent fasting may have a protective effect against skin aging in aging mouse model, manifested by improvements in epidermal and dermal atrophy, as well as the fragmentation and degradation of elastic fibers. The potential mechanism is related to its enhancement of the body's overall antioxidant capacity.

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