Extracellular vesicles, which are highly conserved in most cells, contain biologically active substances. The vesicles and substances interact with cells and impact physiological mechanisms. The skin is the most external organ and is in direct contact with the external environment. Photoaging and skin damage are caused by extrinsic factors. The formation of wrinkles is a major indicator of skin aging and is caused by a decrease in collagen and hyaluronic acid. MMP-1 expression is also increased. Due to accruing damage, skin aging reduces the ability of the skin barrier, thereby lowering the skin’s ability to contain water and increasing the amount of water loss. L. plantarum suppresses various harmful bacteria by secreting an antimicrobial substance. L. plantarum is also found in the skin, and research on the interactions between the bacteria and the skin is in progress. Although several studies have investigated L. plantarum, there are only a limited number of studies on extracellular vesicles (EV) derived from L. plantarum, especially in relation to skin aging. Herein, we isolated EVs that were secreted from L. plantarum of women in their 20s (LpEVs). We then investigated the effect of LpEVs on skin aging in CCD986sk. We showed that LpEVs modulated the mRNA expression of ECM related genes in vitro. Furthermore, LpEVs suppressed wrinkle formation and pigmentation in clinical trials. These results demonstrated that LpEVs have a great effect on skin aging by regulating ECM related genes. In addition, our study offers important evidence on the depigmentation effect of LpEVs.

Human hair follicle dermal papilla cells (HFDPCs) located in hair follicles (HFs) play a pivotal role in hair follicle morphogenesis, hair cycling, and hair growth. Over the past few decades, probiotic bacteria (PB) have been reported to have beneficial effects such as improved skin health, anti-obesity, and immuno-modulation for conditions including atopic dermatitis and inflammatory bowel disease (IBD). PB can secrete 50~150 nm sized extracellular vesicles (EVs) containing microbial DNA, miRNA, proteins, lipids, and cell wall components. These EVs can regulate communication between bacteria or between bacteria and their host. Although numerous biological effects of PB-EVs have been reported, the physiological roles of Leuconostoc holzapfelii (hs-Lh), which is isolated from human scalp tissue, and the extracellular vesicles derived from them (hs-LhEVs) are largely unknown. Herein, we investigated the effects of hs-LhEVs on hair growth in HFDPCs. We show that hs-LhEVs increase cell proliferation, migration, and regulate the cell cycle. Furthermore, hs-LhEVs were found to modulate the mRNA expression of hair-growth-related genes in vitro. These data demonstrate that hs-LhEVs can reduce apoptosis by modulating the cell cycle and promote hair growth by regulation via the Wnt/β-catenin signal transduction pathway.

The process of skin aging is intricate, involving intrinsic aging, influenced by internal factors, and extrinsic aging, mainly caused by exposure to UV radiation, resulting in photoaging. Photoaging manifests as skin issues such as wrinkles and discoloration. The skin microbiome, a diverse community of microorganisms on the skin’s surface, plays a crucial role in skin protection and can be affected by factors like humidity and pH. Probiotics, beneficial microorganisms, have been investigated for their potential to enhance skin health by regulating the skin microbiome. This can be accomplished through oral probiotics, impacting the gut–skin axis, or topical applications introducing live bacteria to the skin. Probiotics mitigate oxidative stress, suppress inflammation, and maintain the skin’s extracellular matrix, ultimately averting skin aging. However, research on probiotics derived from human skin is limited, and there is no established product for preventing photoaging. The mechanism by which probiotics shield the skin microbiome and skin layers from UV radiation remains unclear. Recently, researchers have discovered Lactobacillus in the skin, with reports indicating a decrease in this microorganism with age. In a recent study, scientists isolated Lactobacillus iners KOLBM20 from the skin of individuals in their twenties and confirmed its effectiveness. A comparative analysis of genetic sequences revealed that strain KOLBM20 belongs to the Lactobacillus genus and closely relates to L. iners DSM13335(T) with a 99.20% similarity. Importantly, Lactobacillus iners KOLBM20 displayed anti-wrinkle properties by inhibiting MMP-1. This investigation demonstrated the inhibitory effect of KOLBM20 strain lysate on MMP-1 expression. Moreover, the data suggest that KOLBM20 strain lysate may prevent UVB-induced MMP-1 expression by inhibiting the activation of the ERK, JNK, and p38 signaling pathways induced by UVB. Consequently, KOLBM20 strain lysate holds promise as a potential therapeutic agent for preventing and treating skin photoaging.

Rising global temperatures increase skin exposure to heat stress, which can impair skin structure and function. While several cosmetic ingredients have been developed to mitigate heat-induced damage, most primarily aim to enhance hydration or suppress inflammation, lacking mechanistic insights into their action under heat stress. This study assessed E. artemiae-derived SUPER-T and its exosome form, Thermasome, in heat-stressed human skin fibroblasts. Transcriptomic profiling revealed that heat stress upregulated heat-related thermal receptors and downregulated key extracellular matrix (ECM)-related genes. Notably, treatment with SUPER-T upregulated expression of these genes, suggesting a reparative role as a barrier to alleviate heat stress at the dermal–epidermal junction. For its application in a field of cosmetics, SUPER-T encapsulated in exosomes (Thermasome) enhanced the heat resilience, suggesting its better transdermal and heat protective effects. Thermasome further improved skin heat resilience and enhanced ECM gene expression including collagen genes. Our findings provide a mechanistic basis for the development of functional cosmetical materials that target ECM remodeling under heat-stressed conditions.

Several plant-derived metabolites that enhance plant resilience in response to biotic and abiotic stresses have been developed as senolytics after their apoptotic effects were discovered. Several ginsenosides have also been reported to exert apoptotic effects. We therefore hypothesized that ginsenosides from wild P. ginseng, which survives for long periods in harsh environments, may act as senolytics for skin longevity. The phytochemical characteristics of wild P. ginseng were investigated by LC–MS/MS-based comparison of 38 ginsenosides between cultivated and wild P. ginseng. Wild P. ginseng had a 2.7-fold higher total ginsenoside content in the underground parts. Intermediate ginsenoside metabolites, particularly ginsenoside C-Mc₁, were especially abundant and characteristic of wild P. ginseng. To isolate trace amounts of ginsenoside C-Mc₁, adventitious roots were mass-cultured from tissue segments of wild P. ginseng. The cultured roots were subjected to a four-step column chromatography procedure (HP-20, silica gel twice, and reversed-phase) to obtain both a crude saponin fraction and purified ginsenoside C-Mc₁. These were then combined to prepare a C-Mc₁-fortified ginsenoside preparation derived from wild ginseng adventitious roots, designated wild ginseng ginsenosides (WGGs), thereby increasing the level of the naturally occurring characteristic metabolite C-Mc₁. The senolytic activity of WGGs was evaluated in senescence-induced fibroblasts. While WGGs maintained apoptotic cell levels in normal fibroblasts at 8–9%, they increased apoptosis in senescent fibroblasts to 18.4–25.9%, corresponding to a 1.3–1.8 fold increase over the negative control (14.4%). This study delineates the ginsenoside profile of wild P. ginseng and suggests the potential of sustainably produced WGGs as senolytics for skin aging. Graphical abstract

Injected botulinum neurotoxins (BoNT) reduce dynamic wrinkles by cleaving SNARE proteins at the neuromuscular junction; however, their large size mostly limits their use to injectable procedures. Certain polyphenols, including myricetin, have been shown in neuronal systems to reduce acetylcholine (ACh)-induced muscle contraction via inhibition of SNARE complex zippering, suggesting potential for topical use as modulators of skin cholinergic activity. This study aimed to identify a natural extract blend similarly capable of attenuating ACh release followed by characterization of the activity of this extract on human skin explants, alongside reference molecules BoNT/A, α-bungarotoxin, and myricetin. The natural extract blend (“Blend 1”) inhibited vesicle fusion and attenuated norepinephrine release in a cell culture system, inhibited muscle cell contraction within nerve/muscle co-culture, and attenuated ACh release consistent with myricetin and reference neurotoxins within human skin explants. Bulk transcriptomics of treated ex vivo skin explants revealed that BoNT/A, myricetin and Blend 1 all shared a similar downregulated inflammatory and anti-viral gene profile separate from α-bungarotoxin, but that myricetin and Blend 1 shared a large degree of overlap for upregulated genes associated with skin homeostasis and repair that was not observed for either toxin. These data support Blend 1 as a candidate for topical cosmetic use through modulation of BoNT/A-like cholinergic pathways, alongside activation of additional pathways associated with skin homeostasis and repair.