Oxidative stress caused by reactive oxygen species (ROS) is one of the major causes of senescence. Strategies to reduce ROS are known to be important factors in reversing senescence, but effective strategies have not been found. In this study, we screened substances commonly used as cosmetic additives to find substances with antioxidant effects. Polygonum cuspidatum (P. cuspidatum) extract significantly reduced ROS levels in senescent cells. A novel mechanism was discovered in which P. cuspidatum extract reduced ROS, a byproduct of inefficient oxidative phosphorylation (OXPHOS), by increasing OXPHOS efficiency. The reduction in ROS by P. cuspidatum extract restored senescence-associated phenotypes and enhanced skin protection. Then, we identified polydatin as the active ingredient of P. cuspidatum extract that exhibited antioxidant effects. Polydatin, which contains stilbenoid polyphenols that act as singlet oxygen scavengers through redox reactions, increased OXPHOS efficiency and subsequently restored senescence-associated phenotypes. In summary, our data confirmed the effects of P. cuspidatum extract on senescence rejuvenation and skin protection through ROS reduction. This novel finding may be used as a treatment in senescence rejuvenation in clinical and cosmetic fields.

Background: Reactive oxygen species (ROS) generated by mitochondrial dysfunction damage cellular organelles and contribute to skin aging. Therefore, strategies to reduce mitochondrial ROS production are considered important for alleviating skin aging, but no effective methods have been identified. Methods: In this study, we evaluated substances utilized as cosmetic ingredients and discovered Camellia sinensis (C. sinensis) as a substance that reduces mitochondrial ROS levels. Results: C. sinensis extracts were found to act as senolytics that selectively kill senescent fibroblasts containing dysfunctional mitochondria. In addition, C. sinensis extracts facilitated efficient electron transport in the mitochondrial electron transport chain (ETC) by increasing the efficiency of oxidative phosphorylation (OXPHOS), thereby reducing mitochondrial ROS production, a byproduct of the inefficient ETC. This novel mechanism of C. sinensis extracts led to the restoration of skin aging and the skin barrier. Furthermore, epigallocatechin gallate (EGCG) was identified as an active ingredient that plays a key role in C. sinensis extract-mediated skin aging recovery. Indeed, similar to C. sinensis extracts, EGCG reduced ROS and improved skin aging in an artificial skin model. Conclusions: Our data uncovered a novel mechanism by which C. sinensis extract reverses skin aging by reducing mitochondrial ROS production via selective senescent cell death/increased OXPHOS efficiency. Our results suggest that C. sinensis extract or EGCG may be used as a therapeutic agent to reverse skin aging in clinical and cosmetic applications.

Reactive oxygen species (ROS) are a major cause of skin aging, leading to oxidation and cleavage of collagen that supports skin structure. Previous studies have demonstrated that Magnolia officinalis var. officinalis (M. officinalis) dry extract reduces mitochondria-enriched ROS production and improves senescence-related phenotypes in vitro. However, its effects on human skin aging have not been investigated. In this study, we conducted both in vitro and clinical trials using an M. officinalis liquid extract, which can be directly applied to cosmetic formulations. The M. officinalis liquid extract restored mitochondrial function and reduced mitochondria-enriched ROS production. Furthermore, M. officinalis liquid extract activated mitophagy, which removes defective mitochondria, a major source of ROS production. In clinical trials, the M. officinalis liquid extract reduced the mean depth of neck wrinkles by 12.73% and the maximum depth by 17.44%. It also reduced the mean roughness (Ra), root mean square roughness (Rq), and maximum depth of roughness (Rmax) by 12.73%, 10.16%, and 10.81%, respectively. Furthermore, the key to the skin-improving effects of M. officinalis liquid extract lies in its ability to increase skin elasticity by 3.76% and brighten skin tone by 0.76%. In conclusion, this study identified a novel mechanism by which M. officinalis liquid extract rejuvenates skin aging. M. officinalis can be utilized as a cosmetic ingredient to improve skin aging and therapeutic candidate for the development of anti-aging treatments.

Oxidative stress induced by reactive oxygen species (ROS) is a major contributor to senescence. Although strategies to mitigate ROS are considered crucial for reversing this process, effective interventions remain limited. Extracts from Polygonum cuspidatum (P. cuspidatum) have shown protective effects against senescence by suppressing mitochondrial ROS production; however, the specific bioactive compound responsible for these effects has not yet been identified. This study aimed to identify the active compound in P. cuspidatum responsible for reducing mitochondrial ROS and to elucidate its mechanism of action in rejuvenating senescence. Bioactive components of P. cuspidatum extract were screened for their ability to decrease mitochondrial ROS production. The most potent compound, 2-methoxystypandrone (2-MS), was further examined for its effects on oxidative phosphorylation (OXPHOS) efficiency, mitochondrial ROS generation, and senescence-associated phenotypes in a skin cell-based model. 2-MS was identified as the most effective compound for reducing mitochondrial ROS. Mechanistically, 2-MS enhanced OXPHOS efficiency, thereby minimizing ROS production resulting from inefficient respiration. Reduction in mitochondrial ROS by 2-MS restored senescence-associated phenotypes and rejuvenated senescence by suppressing ROS-driven melanogenesis and inflammatory responses in skin cells. This study identifies 2-MS as a key active ingredient of P. cuspidatum that exerts anti-aging effects through the reduction in mitochondrial ROS generation. These findings highlight 2-MS as a promising therapeutic and cosmetic candidate for rejuvenating senescence.

Background: Collagen, a major structural component of the skin, decreases with age and is associated with wrinkles, reduced elasticity, sagging, and dryness. While hydrolyzed or marine‐derived collagens are widely used in cosmetics, advances in biotechnology have enabled the development of bio‐collagen peptides. However, the role of collagen type V–derived peptides in skin biology remains largely unexplored. Aims: In this study, we generated human‐like collagen alpha‐1 type V peptides (hCOLVp) and investigated their effects on skin‐related parameters. Patients/Methods: COL5A1‐derived peptides with optimized sequences were generated, and a single candidate was identified through screening. Protein expression of collagen types I, III, XVII, and laminin 5 was evaluated in human dermal fibroblasts or keratinocytes. A collagen gel contraction assay and SEM‐based microstructural analysis were performed. Finally, a reconstructed human full‐thickness skin (RS) model was used to assess peptide penetration and barrier‐associated proteins. Results: hCOLVp increased expression of collagen types I, III, XVII, and laminin 5. Treated collagen gels showed greater contractile force and higher fiber density than controls. In RS models, hCOLVp penetrated over time and was associated with increased collagen fibers and upregulated expression of involucrin and transglutaminase‐1 (TGase‐1), both related to barrier function. In a preliminary clinical trial, hCOLVp improved skin barrier properties, density, and elastic recovery. Conclusion: These findings suggest that hCOLVp contributes to strengthening dermal and epidermal structural networks, thereby supporting skin function and resilience.