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) contribute to aging by mainly damaging cellular organelles and DNA. Although strategies to reduce ROS production have been proposed as important components of anti-aging therapy, effective mechanisms to lower ROS levels have not yet been identified. Here, we screened natural compounds frequently used as cosmetic ingredients to find substances that reduce ROS levels. Magnolia officinalis (M. officinalis) extract significantly lowered the levels of ROS in senescent fibroblasts. A novel mechanism by which M. officinalis extract restores mitochondrial function to reduce ROS, a byproduct of inefficient electron transport, was discovered. The reduction of ROS by M. officinalis extracts reversed senescence-associated phenotypes and skin aging. Then, honokiol was demonstrated as a core ingredient of M. officinalis extract that exhibits antioxidant effects. Honokiol functions as an oxygen radical scavenger through redox processes, also significantly reduced ROS levels by restoring mitochondrial function. In summary, our study identified a novel mechanism by which M. officinalis extract reverses aging and skin aging by reducing ROS through restoring mitochondrial function. These new findings will not only expand our understanding of aging and associated diseases, but also provide new approaches to anti-aging treatments.

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.

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.