Cellular senescence and aging result in a reduced ability to manage persistent types of inflammation. Thus, the chronic low-level inflammation associated with aging phenotype is called “inflammaging”. Inflammaging is not only related with age-associated chronic systemic diseases such as cardiovascular disease and diabetes, but also skin aging. As the largest organ of the body, skin is continuously exposed to external stressors such as UV radiation, air particulate matter, and human microbiome. In this review article, we present mechanisms for accumulation of senescence cells in different compartments of the skin based on cell types, and their association with skin resident immune cells to describe changes in cutaneous immunity during the aging process.

Keloid scarring is a fibroproliferative disease caused by aberrant genetic activation with an unclear underlying mechanism. Genetic predisposition, aberrant cellular responses to environmental factors, increased inflammatory cytokines and epithelial–mesenchymal transition (EMT) phenomena are known as major contributors. In this study, we aimed to identify the molecular drivers that initiate keloid pathogenesis. Bulk tissue RNA sequencing analyses of keloid and normal tissues along with ex vivo and in vitro tests were performed to identify the contributing genes to keloid pathogenesis. An animal model of inflammatory keloid scarring was reproduced by replication of a skin fibrosis model with intradermal bleomycin injection in C57BL/6 mice. Gene set enrichment analysis revealed upregulation of Wnt family member 5A (WNT5A) expression and genes associated with EMT in keloid tissues. Consistently, human keloid tissues and the bleomycin-induced skin fibrosis animal model showed significantly increased expression of WNT5A and EMT markers. Increased activation of the interleukin (IL)-6/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and subsequent elevation of EMT markers was also observed in keratinocytes co-cultured with WNT5A-activated fibroblasts or keloid fibroblasts. Furthermore, WNT5A silencing and the blockage of IL-6 secretion via neutralizing IL-6 antibody reversed hyperactivation of the STAT pathway and EMT markers in keratinocytes. Lastly, STAT3 silencing significantly reduced the EMT-like phenotypes in both keratinocytes and IL-6-stimulated keratinocytes. Intercellular communication via the WNT5A and STAT pathways possibly underlies a partial mechanism of EMT-like phenomena in keloid pathogenesis. IL-6 secreted from WNT5A-activated fibroblasts or keloid fibroblasts activates the JAK/STAT signaling pathway in adjacent keratinocytes which in turn express EMT markers. A better understanding of keloid development and the role of WNT5A in EMT will promote the development of next-generation targeted treatments for keloid scars.

The glycation process has been recognized as one of the critical parameters that accelerate signs of skin aging, especially in skin exposed to environment factors, such as ultraviolet radiation. Although previous studies showed the anti-inflammatory and antiaging properties of the hydrolyzed collagen tripeptide (CTP), its exact mechanism is not fully understood. Therefore, in this study, we sought to investigate the effect of a topical CTP on facial skin. Our group designed a 4 week prospective, single-arm study of 22 Asian women who applied topical CTP. We observed significant improvements in skin wrinkles, elasticity, and density with a reduction in skin accumulation of advanced glycated end products (AGEs) at week 4 without any adverse effects. The in vitro study revealed a preventive effect of the topical CTP on the accumulation of AGEs, denatured collagen production, and reactive oxygen species in dermal fibroblasts. Moreover, treatment with the CTP decreased induction of matrix metalloproteinases while increasing the collagen 1 level. These results suggest that the application of a topical CTP might improve clinical aging phenotypes via the inhibition of glycation and oxidative stress, leading to a delay in cellular aging.

Background: Oral collagen peptides supplementation was reported to improve skin integrity and counteract skin aging.Aims: A randomized, double‐blinded, placebo‐controlled study was conducted to clinically evaluate the impact of low‐molecular‐weight collagen peptides on the human skin.Patients/Methods: Healthy adult participants (n = 100) were randomly assigned to receive a test product containing low‐molecular‐weight collagen peptides or a placebo. Parameters of skin wrinkles, elasticity, hydration, and whitening (melanin and erythema indexes) were measured at baseline and after 4, 8, and 12 weeks.Results: Compared with the placebo group, the average skin roughness, maximum of all peak‐to‐valley values, maximum peak height of the wrinkle, and average maximum height of the wrinkle were significantly improved in the test group. Parameters of skin elasticity, including overall elasticity, net elasticity, and biological elasticity, were also significantly improved in the test group at Week 12 as compared with the placebo group. Moreover, skin hydration and whitening parameters changed more significantly in the test group than in the placebo group. None of the participants experienced adverse events related to the test product.Conclusions: Taken together, these findings suggest that low‐molecular‐weight collagen peptides supplementation can safely ehance human skin wrinkling, hydration, elasticity, and whitening properties.

The present study investigated the effect of topical application of Epidermidibacterium Keratini (EPI-7) ferment filtrate, which is a postbiotic product of a novel actinobacteria, on skin aging, by performing a prospective randomized split-face clinical study on Asian woman participants. The investigators measured skin biophysical parameters, including skin barrier function, elasticity, and dermal density, and revealed that the application of the EPI-7 ferment filtrate-including test product resulted in significantly higher improvements in barrier function, skin elasticity, and dermal density compared to the placebo group. This study also investigated the influence of EPI-7 ferment filtrate on skin microbiome diversity to access its potential beneficial effects and safety. EPI-7 ferment filtrate increased the abundance of commensal microbes belonging to Cutibacterium, Staphylococcus, Corynebacterium, Streptococcus, Lawsonella, Clostridium, Rothia, Lactobacillus, and Prevotella. The abundance of Cutibacterium was significantly increased along with significant changes in Clostridium and Prevotella abundance. Therefore, EPI-7 postbiotics, which contain the metabolite called orotic acid, ameliorate the skin microbiota linked with the aging phenotype of the skin. This study provides preliminary evidence that postbiotic therapy may affect the signs of skin aging and microbial diversity. To confirm the positive effect of EPI-7 postbiotics and microbial interaction, additional clinical investigations and functional analyses are required.