Background/Objectives: Dihydromyricetin (DHM), a flavonoid with abundant natural sources, potent bioactivity, and high safety, holds promise for translational applications, particularly in mitigating skin aging. However, its role and underlying mechanisms in counteracting skin aging induced by advanced glycation end products (AGEs) remain unclear. Methods: Eight-week-old male Sprague-Dawley (SD) rats were subcutaneously injected with 500 mg/kg D-galactose and administered DHM via gavage for 11 weeks. Additionally, senescent human skin fibroblasts (HFF-1) induced by AGEs were used for further investigation. Results: DHM treatment significantly alleviated D-galactose-induced skin aging in rats, with the most pronounced effects observed in the moderate-dose group (100 mg/kg). Compared to the aging group, DHM enhanced skin elasticity and preserved collagen levels. Moreover, DHM promoted cell proliferation in the skin. Further studies on AGE-induced senescent fibroblasts revealed that DHM markedly reduced multiple senescence-associated markers and stimulated cell proliferation by approximately a 1.5-fold increase. Transcriptomic analysis indicated that DHM upregulated genes related to the cell cycle and DNA repair while suppressing AGE-RAGE signaling and its downstream pathways. Notably, DHM downregulated AGER, the gene encoding the receptor for AGEs (RAGE). Molecular docking analysis demonstrated that DHM shares a binding site with other known RAGE inhibitors. Surface plasmon resonance (SPR) analysis further confirmed the high binding affinity of DHM to RAGE (K_D = 28.7 μM), which was stronger and more stable than that of FPS-ZM1 (K_D = 40.7 μM). Conclusions: DHM may attenuate glycation-induced skin aging in rats by functioning as a RAGE inhibitor, thereby suppressing AGE-RAGE signaling, delaying cellular senescence, and promoting cell proliferation.

Background/Objectives: This study aimed to investigate the association between dietary intake and the risk of type 2 diabetes mellitus (T2DM) in a rural northern Chinese population, and to explore potential gene–diet interactions that may influence T2DM susceptibility. Methods: A total of 1747 participants (1138 with T2DM and 609 without) were included, using baseline data from a family-based cohort study in rural northern China. Demographic characteristics, lifestyle factors, and medical history were collected via standardized questionnaires. Dietary intake was assessed using a semi-quantitative food frequency questionnaire, and anthropometric measurements were conducted according to standardized protocols. Based on findings from previous genome-wide association studies, several T2DM-related single-nucleotide polymorphisms were selected for genotyping. Generalized linear models accounting for familial clustering were employed to examine the associations between dietary intake and T2DM risk, and to assess gene–diet interaction. Results: A significant inverse association was observed between fruit intake and T2DM risk. Furthermore, a significant interaction was found between fruit consumption and the CMIP rs2925979 polymorphism: the protective effect of higher fruit intake was evident among individuals carrying the T allele but not among those with the CC genotype. Conclusions: These findings suggest that genetic variation may modify metabolic responses to dietary factors, particularly fruit intake. The results underscore the importance of considering gene–diet interactions in the prevention of T2DM.