Objective: Mitochondrial dysfunction^[1-2] is not only associated with various systemic diseases but also closely related to skin aging and skin conditions (such as melasma, acne, psoriasis, etc.). Mitochondrial dysfunction can lead to decreased energy metabolism, weakened antioxidant capacity, and accelerated apoptosis in skin cells, thereby causing problems such as skin sagging, increased wrinkles, and pigmentation. In contrast, through the synergistic action of multiple active ingredients, it is possible to comprehensively improve the energy metabolism of skin cell mitochondria, ATP production, NAD⁺ levels per unit protein, mitochondrial morphology, and mitochondrial autophagy^[3-5], thereby effectively repairing mitochondrial dysfunction: 1% Polyglycan® Probiotic PDRN (component content includes: hydrolyzed DNA 0.01-0.06%), 1% Polyglycan® Microspherical PDRN (component content: mannitol 55%, trehalose 30%, sodium DNA 10%, sodium hyaluronate 5%), 1% Polyglycan® Ginseng Root Extract (component content includes: ginseng root extract 95-96.8%), 0.35% Polyglycan® Red Ginseng Fermentation Vesicles (lactobacillus fermentation lysate 59.8-61.8%, lactobacillus/ginseng root fermentation filtrate 35-37%). This combination system, as a topical formulation, achieves the effect of repairing mitochondrial dysfunction. This technology stands out with its natural, convenient, non-invasive, and long-lasting effects, fundamentally solving skin aging problems and providing consumers with a safer, more comfortable, and comprehensive anti-aging experience. Methods: The raw materials of dual-ball PDRN (Polydeoxyribonucleotide) and dual-vesicles were dissolved and uniformly dispersed in a pre-designed matrix system separately to prepare a stable combination system for later use. Human dermal fibroblasts were exposed to UVA (ultraviolet A) irradiation to induce cellular damage and simulate a state of cellular stress. On this basis, the concentration of NAD⁺ (nicotinamide adenine dinucleotide) per unit protein, the content of ATP (adenosine triphosphate), and the changes in mitochondrial morphology were detected to systematically evaluate the regulatory effects of the combination system on mitochondrial function. The regulatory effects of the combination system on autophagy were assessed by detecting the changes in LC3b (Microtubule-Associated Protein 1 Light Chain 3B) content. Through the above methods, the biological effects of the dual-ball PDRN and dual-vesicle combination system at the cellular level were comprehensively explored. Results:Based on UVA-irradiated fibroblasts, the concentration of NAD⁺ per unit protein significantly increased by 29.52% and the content of ATP significantly increased by 105.88% after 24 hours of treatment with the combination. Mitochondrial morphology within the cells appeared as elongated rods, with normal fusion and fission occurring. After 48 hours of treatment, the concentration of NAD⁺ per unit protein significantly increased by 34.86% and the content of ATP significantly increased by 141.03%. Based on fibroblasts, the content of human microtubule-associated protein 1 light chain 3b (LC3b) significantly increased by 102.00% after 24 hours of treatment with the combination. Conclusion: In this study, the effects of the dual-ball PDRN and dual-vesicle combination system on mitochondrial function in fibroblasts were investigated. The results demonstrated that the combination system could improve mitochondrial morphology, increase the concentration of NAD⁺ per unit protein and the content of ATP, indicating its regulatory role on mitochondrial function. Additionally, it could enhance the content of human microtubule-associated protein 1 light chain 3b (LC3b), showing its regulatory effect on autophagy.