Nae-Gyu Kang

Ultraviolet (UV)-induced photodamage drives oxidative stress, DNA damage, and chronic inflammation, leading to progressive cellular ultrastructure and skin function degeneration. Despite the potential of probiotics as anti-photodamage agents, their nanoscale action mechanism remains unexplored. Here, we utilize super-resolution fluorescence microscopy to investigate the cellular and molecular basis of Lactobacillus plantarum -derived extracellular vesicles ( L. plantarum EVs) in mitigating photodamage. We showed that UV irradiation triggered extensive organellar remodeling along with elevated reactive oxygen species production, DNA damage signaling, and inflammatory activation. Remarkably, pre- and posttreatment with L. plantarum EVs preserved organelle integrity and restored native nanoscale architecture. Additionally, EV treatment delayed UV-induced PARP-1 activation and nuclear condensate clustering, while suppressing NF-κB translocation and downstream inflammatory cytokine expression. These findings establish probiotic-derived EVs as modulators of stress-responsive signaling and structural homeostasis during UV-induced photodamage. By providing a super-resolution mechanistic framework for understanding probiotic EV-mediated modulation of cellular photodamage responses, this study provides a basis for future investigation of EV-based strategies for skin protection.

Elastic fibers are key components of the skin extracellular matrix and are essential for maintaining skin integrity and elasticity. During skin aging, particularly photoaging, elastic fiber integrity is progressively compromised by increased elastase activity and the downregulation of elastin and scaffold-related gene expression. Therefore, effective strategies to preserve elastic fiber function should address not only elastin synthesis but also enzymatic degradation and scaffold integrity. In this study, we investigated a multitarget approach to restoring the elastic fiber network by modulating elastin production, elastase activity, and scaffold protein expression. We found that Copper Tripeptide-1 enhanced elastin expression and secretion, ethyl ferulate inhibited elastase activity, and cedrol promoted scaffold-related gene expression and microfibrillar protein restoration in dermal fibroblasts. To assess the biological relevance of this approach, the combined treatment was evaluated using UV-damaged human skin biopsy samples. This combination effectively mitigated UV-induced elastic fiber disruption and significantly improved fiber architecture, as confirmed by immunofluorescence staining and scanning electron microscopy. These findings indicate that coordinated modulation of elastin production, proteolytic protection, and scaffold reinforcement is essential for maintaining elastic fiber integrity and represents a promising approach for preserving skin elasticity during aging.

Background: Chlorogenic acid (CGA) and taurine are well-known antioxidant compounds reported to reduce skin cellular senescence. However, the biological mechanisms underlying their skin-protective effects remain unclear. Methods: In this study, we conducted transcriptome-wide RNA sequencing to profile gene expression changes in human epidermal keratinocytes, melanocytes, and fibroblasts following treatment with CGA, taurine, or their combination. To identify aging-related genes, we integrated evidence from aging databases, perceived-age GWAS, enrichment in aging-related gene ontology and pathways, and drug-gene interaction annotations. Validation of representative genes was performed using quantitative real-time PCR. Results: A total of 197 differentially expressed genes (DEGs) were identified, of which 62 were prioritized as aging-related DEGs (AR-DEGs) based on their relevance to skin aging anti-senescence-associated pathways, highlighting regulatory transcription factors including TGFB2 , ETS1 , and EGR1 . Co-treatment enhanced the transcriptional effects of CGA and taurine, with several genes exhibiting synergistic responses. Targeted transcriptome-wide association analysis indicated potential links between specific AR-DEGs, such as FST, and phenotypes including perceived age and skin pigmentation. Conclusion: By identifying key genes and pathways that contribute to cellular longevity in human skin, this study provides molecular insights for developing anti-aging strategies with potential applications in dermatology.

Skin aging is characterized by fibroblast senescence, extracellular matrix (ECM) degradation, and impaired wound healing, driven by oxidative stress and telomere dysfunction. Here, we investigated the anti-aging effects of a standardized microwave-assisted propolis extract (MAPE) in both H₂O₂-induced and replicative senescence models of human dermal fibroblasts (HDFs). MAPE significantly reduced reactive oxygen species (ROS) accumulation and enhanced antioxidant gene expression (NQO1, GCLM), indicating activation of NRF2-dependent defense pathways. It suppressed senescence markers (CDKN2A, CDKN1A, IL6), decreased SA-β-gal activity, and attenuated inflammaging. Moreover, MAPE inhibited MMP1 expression, restored COL1A1, and improved fibroblast wound closure, thereby maintaining ECM homeostasis. Importantly, MAPE modulated Wnt/β-catenin signaling by upregulating WNT3A and LEF1 while suppressing DKK1, and increased TERT expression, suggesting involvement of telomerase-related regulatory pathways. These effects resembled those of CHIR99021, a canonical Wnt activator, while providing additional antioxidant protection. Together, our findings suggest that MAPE is a propolis-derived bioactive ingredient that counteracts fibroblast senescence through coordinated modulation of NRF2 and Wnt/β-catenin–TERT signaling pathways, supporting its potential as a cosmeceutical ingredient for mitigating skin aging.

Current alopecia treatments have side effects and limited efficacy, highlighting the need for better alternatives. Estrogen and estrogen receptor alpha (ERα)-targeting therapies have shown promise in addressing female-pattern hair loss, outperforming some conventional options. This study investigated the hair growth-promoting effects of Cnidium officinale extract (COE) and its active compound, ferulic acid (FA), focusing on their role in activating ERα. Using human dermal papilla cells (DPCs) and cultured human hair follicles, we assessed cell proliferation, mitochondrial function, gene expression, and protein levels including transcriptome analysis. Both COE and FA significantly enhanced DPCs proliferation and mitochondrial activity, and extended hair follicle length during the anagen (growth) phase. Transcriptomic comparisons between FA- and estrogen-treated cells revealed upregulation of genes involved in energy metabolism, particularly those related to ATP regeneration. FA also elevated c-JUN mRNA expression, indicating estrogen-like ERα activation, and increased the expression of MAPK pathway-associated proteins, along with key growth factors. Additionally, co-treatment with FA and NMN, a cellular activity regulator, enhanced mitochondrial activity in a concentration-dependent manner beyond NMN alone. These findings suggest that COE and FA stimulate hair growth by enhancing DPCs function, with FA’s ERα-activating properties offering potential as a novel therapeutic option for alopecia.

Background: The periorbital skin area is particularly susceptible to aging compared to other facial regions due to its unique anatomical features and frequent muscle movements. This leads to early development of wrinkles and discoloration, which affect one’s appearance. Because of these characteristics, the eye-region skin serves as a representative indicator reflecting both skin aging and overall health status. Objectives: This study aims to develop and validate a straightforward, non-invasive method to evaluate changes in the eye-region skin as reliable markers of aging and overall physiological condition. Methods: We analyzed facial images from 2,515 Korean women aged 20–69 and evaluated various periorbital features, including wrinkles, morphological characteristics, and pigmented spots, using skin measurement devices and computational image analysis techniques. To assess skin aging and health status, we developed age prediction models based on different combinations of these periorbital features for each individual. Subsequently, Principal Component Analysis (PCA) was performed to summarize disease history variables for each participant, and the correlation between the first principal component (PC1) and periorbital skin age was evaluated using Pearson correlation analysis. Results: Periorbital skin features showed significant associations with chronological age. We developed nine distinct age prediction models by combining different subsets of these features, each producing a unique aging score. Among them, seven models demonstrated strong correlations with actual age (r > 0.7), confirming their predictive reliability. These individual model outputs were collectively considered as unified aging markers representing periorbital skin age. To evaluate clinical relevance, we analyzed the association between periorbital skin age derived from the model incorporating all skin features and disease history. Periorbital skin age showed significant associations with five out of seven diseases individually, as well as with the PC1 summarizing all disease histories collectively. Conclusion: This study establishes ‘periorbital skin age’ as a non-invasive biomarker that effectively reflects both the progression of skin aging and underlying medical conditions. Our findings highlight the potential utility of eye-region skin assessment in clinical and health monitoring settings, offering a practical tool for evaluating physiological aging and disease risk.

With the aging global population, interest in skin aging and skin health products is increasing. Nelumbo nucifera Gaertn. (lotus) has been widely used for its pharmacological benefits, including antioxidant, anti-inflammatory, skin-whitening, and anti-aging properties. In this study, we aimed to develop a safe and biologically active extract by extracting lotus flowers with hot water, followed by sequential fractionation using porous resin chromatography with stepwise ethanol elution (100% water and 30%, 70%, and 100% ethanol). The 30% and 70% ethanol fractions showed the highest total polyphenol and flavonoid contents. Liquid chromatography–electrospray ionization–mass spectrometry analysis identified major flavonoids, including myricetin and quercetin derivatives, in these fractions. These fractions were combined to formulate a novel Nelumbo nucifera flower extract (NFE), which exhibited potent antioxidant activity confirmed by 2,2-diphenyl-1-picrylhydrazyl, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and ferric reducing antioxidant power assays. NFE significantly inhibited nitric oxide and prostaglandin E₂ secretion in lipopolysaccharide-activated murine RAW264.7 macrophages. In human keratinocytes HaCaT cells, NFE reduced tumor necrosis factor-α-induced expression and secretion of the pro-inflammatory cytokines interleukin (IL)-6 and IL-8 without cytotoxicity. These findings demonstrate that NFE has strong in vitro antioxidant and anti-inflammatory activities, supporting its potential as a bioactive ingredient for application in improving skin health preparations.

Microcirculation in cutaneous tissue is essential to balance oxygen delivery and maintain the health of the skin. Senescence contributes to microcirculatory dysfunction through mechanisms involving chronic inflammation, structural remodeling of microvessels, and disturbances in hemodynamics. In this study we investigated the promoting effect of escin on blood flow through topical application. To elucidate the molecular mechanisms of escin, kinase phosphorylation changes in human umbilical vein endothelial cells (HUVECs) were examined. Escin stimulates the Wnt/β-Catenin and c-Jun N-terminal kinase (JNK) signaling pathway in cultured HUVECs. To clarify the target of escin in the Wnt/β-Catenin signaling pathway, gene expression in response to escin treatment was evaluated, and escin-mediated signaling activation was accompanied by glycogen synthase kinase-3 beta (Gsk3β), according to inhibitor studies performed with IWR1 (tankyrase inhibitor). In addition, the expression level of the Gsk3β were down-regulated by escin treatment in cultured HUEVCs. Escin also enhanced vascular remodeling, and, when applied topically, led to a sustained increase in cutaneous blood flow. Escin-mediated Wnt signaling activation could enhance blood vessel networks via Gsk3β down-regulation. In conclusion, our data demonstrate that escin promotes angiogenic behavior and enhances adenosine-induced perfusion in humans, thereby supporting its potential role in modulating cutaneous microcirculation.