Search Results (54)

Dermal fibroblasts, the primary stromal cells of the dermis, exhibit remarkable plasticity in response to various stimuli, playing crucial roles in tissue homeostasis, wound healing, and ECM production. This study examines the molecular mechanisms underlying fibroblast plasticity, including key signaling pathways, epigenetic regulation, and microRNA-mediated control. The impact of aging on ECM synthesis and remodeling is discussed, and the diminished production of vital components such as collagen, elastin, and glycosaminoglycans are highlighted, alongside enhanced ECM degradation through upregulated matrix metalloproteinase activity and accumulation of advanced glycation end products. The process of cellular senescence in dermal fibroblasts is explored, with its role in skin aging and its effects on tissue homeostasis and repair capacity being highlighted. The senescence-associated secretory phenotype (SASP) is examined for its contribution to chronic inflammation and ECM disruption. This review also presents therapeutic perspectives, focusing on senolytics and geroprotectors as promising strategies to combat the negative effects of fibroblast senescence. Current challenges in translating preclinical findings to human therapies are addressed, along with future directions for research in this field. This comprehensive review explores the complex interplay between dermal fibroblast plasticity, cellular senescence, and extracellular matrix (ECM) remodeling in the context of skin aging. In conclusion, understanding the complex interplay between dermal fibroblast plasticity, cellular senescence, and extracellular matrix (ECM) remodeling is essential for developing effective anti-aging interventions, which highlights the need for further research into senolytic and geroprotective therapies to enhance skin health and longevity. This approach has shown promising results in preclinical studies, demonstrating improved skin elasticity and reduced signs of aging. Full article

The ultraviolet (UV) component of solar radiation is a major risk factor for the development of skin ailments, ranging from erythema in acute cases to premature skin aging and skin cancer in chronic reactions. While skin cells show a remarkable protective capacity against solar radiation, there is a growing interest in the use of natural substances for photoprotection purposes. This article describes the molecular and cellular mechanisms underlying UV radiation-induced skin aging, with a particular focus on the potential beneficial effects of hesperidin and its derivatives: hesperetin, hesperidin glucoside, and hesperidin methylchalcone. A review of the literature from the last 20 years reveals a substantial body of experimental evidence supporting the role of hesperidin in protecting the skin against UV radiation, and its effects on skin cells and tissue, including oxidative stress and aging processes. Moreover, flavonoids have other beneficial effects on skin cell vitality by modulating the immune system, metalloproteinases, and angiogenesis. The key mechanisms for the action of hesperidin and its derivatives involve the activation of the Nrf-2/ARE system, the expression of longevity genes CISD2, and interference with the MAP kinase and PI3PK/Akt signal transduction pathways. In murine experimental models, these derivative molecules have a protective role both systemically after dietary intake and through the topical application of dermocosmetic creams. Full article

Atopic Dermatitis (AD) is a common inflammatory skin disease characterized primarily by its chronic and recurrent nature. This has a significant impact on productivity and human longevity. Dysbiosis of gut flora has been demonstrated to be significantly associated with the progression of AD. In our previous research, it was shown that Lactobacillus rhamnosus RL5-H3-005 (RL) and Pediococcus acidilactici RP-H3-006 (RP) have the ability to reduce the risk of disease in AD mice through the gut–mammary axis. Based on our previous work, this study aims to further investigate the effects of kynurenine (KYN), a metabolite of RL and RP, on AD mice induced by 2, 4-dinitrofluorobenzene (DNFB). In this study, we found that supplementing KYN in AD mice effectively alleviates the pathological symptoms of atopic dermatitis and further improves the levels of SCFAs in their intestines. Further research indicates that KYN’s therapeutic effects on AD are primarily manifested in the reduction of secretory immunoglobulin A (sIgA), immunoglobulin E (IgE), interleukin-4 (IL-4), IL-5, IL-13, and thymic stromal lymphopoietin (TSLP) levels in mice, while also repairing the intestinal barrier function of AD mice. Overall, the metabolites KYN of probiotics RL and RP can regulate the levels of SCFAs of mice, potentially improving the symptoms of AD mice through the gut–skin axis. Full article

Scabies and tungiasis are skin-related neglected tropical diseases (NTDs) associated with poverty and poor living conditions. We performed an ecological study covering a state in northeast Brazil to identify socio-economic and environmental factors associated with the occurrence of severe scabies and severe tungiasis, respectively. Data on disease occurrence on the municipality level were derived from a previous study based on online questionnaires. A total of 47 (26.0%) of the 181 state’s municipalities reported severe tungiasis, and 113 (62.4%) severe scabies. Municipalities with occurrence of severe tungiasis were characterized by higher annual rainfalls (median = 883 mm vs. 741 mm; p = 0.037), higher minimum temperatures (median = 23.4 °C vs. 22.7 °C; p = 0.002), higher aridity indices indicating more humid climates (median = 45.1 vs. 50.6; p = 0.019), lower altitudes (median = 88.8 m vs. 201 m; p < 0.001), higher mean air humidity (66.5% vs. 63%; p = 0.018), and better socioeconomic indices (Municipal Human Development Index [MHDI]—median = 0.616 vs. 0.611; p = 0.048/MHDI Longevity—mean = 0.769 vs. 0.759; p = 0.007/Municipal Development Index [MDI]—median = 27.5 vs. 21.8; p < 0.001). Municipalities with predominant luvisol soil characteristics had a lower risk for severe tungiasis (RR = 0.46; 95% CI = 0.27–0.79; p = 0.003), whereas municipalities with predominant gleysols had a significantly higher risk (RR = 2.44; 95% CI = 1.43–4.15; p = 0.010). Municipalities with occurrence of severe scabies were characterized by significantly higher annual rainfalls (median = 804 mm vs. 708 mm; p = 0.001), higher minimum temperatures (23.1 °C vs. 22.3 °C; p < 0.001), higher aridity index (median = 48.2 vs. 41.9; p = 0.014), higher air humidity (65.9% vs. 61%; p = 0.001), lower altitudes (median = 153 m vs. 246 m; p = 0.003), and better socio-economic indicators (MHDI—median = 0.616 vs. 608; p= 0.012/MHDI Education—mean = 0.559 vs. 0.541; p = 0.014/MDI—median = 24.3 vs. 21.1; p = 0.005). In multivariate regression analysis, MDI remained significantly associated with the presence of severe tungiasis in the final model (RR = 1.04; 95% CI: 1.02–1.05; p < 0.001) and the presence of severe scabies with minimum temperature (RR = 1.13; 95% CI: 1.04–1.24; p = 0.003) and aridity index (RR = 1.01; 95% CI: 1.00–1.01; p = 0.004). Our study underscores the importance of environmental and socioeconomic factors for the occurrence of severe scabies and tungiasis in a semi-arid climatic context, offering a perspective for identification of high-risk areas, and providing evidence for the control of skin NTDs withina One Health approach. Full article

This study deals with the extraction of active compounds for a formula (Angelica gigas, Cornus officinalis, Ganoderma lucidum, Thymus vulgaris, and Asparagus cochinchinensis) and the evaluation of its skin anti-aging properties. This formulation was inspired by the oriental medicine Gongjin-dan (Angelica gigas, Cornus officinalis, deer antler, and musk), which has been used as a restorative drug for longevity. Enzyme-based extraction and chemical purification were used to obtain a mixed fraction (GEF) enriched in glycopeptides and glycoproteins from the five herbal materials. The chemical characteristics of GEF, including the carbohydrate groups attached to the peptides and proteins, the total carbohydrate and protein contents, and the composition of monosaccharides and amino acids were determined. The chemical characteristics that were significantly different from those of the extract, generally prepared in the same ratio, were the abundance of glycopeptides and glycoproteins and the high proportions of conditionally essential amino acids (51.0%) and acidic/basic amino acids (67.7%). These are necessary components for strengthening the skin layers against aging. The in vitro skin anti-aging properties of GEF on human fibroblasts (HS68), keratinocytes (HaCaT), and adipose-derived mesenchymal stem cells (ADMSCs) were evaluated. It was found that MMP-1 gene expression was inhibited (18–28%) and fibrillin-1 protein (23–37%) was restored contrary to the effect of UV irradiation. COL1A1 and COL4A1 gene expression (25–35%), HAS2 gene expression (22–213%), and adipogenesis (15%) were facilitated. These results demonstrate the potential of GEF as a raw material for skin anti-aging and reinforce the scientific evidence supporting a traditional medicine with a long history. Full article

Diet is a potential modulator of telomere length (TL), but the impact of individual dietary components, such as nuts, on TL in young, healthy individuals remains underexplored. Peanuts are rich in bioactive compounds that may influence TL. Therefore, to fill this gap of knowledge, this study aimed to investigate the effect of peanut consumption on TL in this specific population. Fifty-eight young, healthy individuals were randomized to one of three different intervention groups for 6 months each: (1) 25 g/day of skin-roasted peanuts (SRP); (2) 32 g/day of peanut butter (PB); (3) 32 g/day of a control butter (CB) (based on peanut oil). TL was measured by quantitative real-time PCR in saliva at baseline and at the end of the intervention. Our findings revealed significant between-group differences in TL changes, particularly between the SRP and CB groups over 6 months (mean difference: 0.53; 95% CI: 0.01, 1.05; p-value = 0.048). No significant difference was observed between PB and CB groups (mean difference: 0.12; 95% CI: –0.42, 0.66; p-value = 0.66). This study provides novel insights into the impact of peanut consumption on TL maintenance in young and healthy individuals. The findings highlight the potential benefits of incorporating peanuts into the diet as a means of promoting cellular health and longevity. Further research is warranted to elucidate the underlying mechanisms and validate these findings across diverse populations and longer time frames. Full article

Aging, marked by a decline in cellular function and increased risk of diseases, involves the accumulation of senescent cells. This study aims to develop and characterize 3D senescent skin models to understand cellular senescence mechanisms’ implications in cutaneous aging. Normal human epidermal keratinocytes (NHEKs) were cultured from early to late passages (p2 to p7) to induce replicative senescence or sourced from both young and aged donors to reconstruct 3D models. Histological analyses assessed tissue morphology and integrity, while permeability assays evaluated epidermal barrier function. Analyses using immunostaining, RT-PCR, Affymetrix™ GeneChip™ Microarrays identified key markers of cellular senescence, epidermal homeostasis, and other related processes. Results showed that NHEKs at p5 and beyond, and those from aged donors, exhibited significant morphological disruptions, decreased expression of differentiation-associated genes, and impaired barrier function. Increased p16ink4a-positive cells indicated enhanced senescence. Transcriptome analysis revealed significant changes in keratinocyte differentiation, cell–cell interaction, cell cycle regulation, extracellular matrix homeostasis, and inflammation. These findings underscore the relevance of addressing cellular senescence for enhancing skin health and promoting skin longevity. These 3D senescent skin models, validated by consistent results from both passage-induced senescence and aged donor keratinocytes, are valuable for understanding skin aging and developing anti-aging treatments, positioning them as essential tools in the pursuit of skin longevity-focused innovations. Full article

The skin is continuously exposed to environmental changes, rendering it vulnerable to damage from external stressors that contribute to premature skin aging. This study aims to explore skin longevity pathways stimulated by a rose extract (RE) derived from petals. Human keratinocytes treated with RE exhibited a significant increase in NRF2 (NF-E2-related factor 2; ≈2–4% of induction) and LAMP2A (Lysosome-Associated Membrane Protein 2A; ≈6–12% of induction) levels. The presence of RE significantly mitigated the increase in carbonylation levels (≈34–37% of protection) and the number of labeled P16^INK4A cells (≈60–72% of protection), associated with proliferation arrest, both induced by exposure to BAP (Benzo[a]pyrene) coupled with UV-A (Ultraviolet A) irradiation. The beneficial effects mediated by RE were inhibited by Compound C, a specific AMPK inhibitor (AMP-activated protein kinase). The involvement of the AMPK pathway in mediating the beneficial effects of RE has been confirmed by assessing its activation through the evaluation of its phosphorylation state which was significantly elevated in the presence of RE compared to the stress condition. In conclusion, the activation of the AMPK pathway enhances antioxidant defenses and promotes autophagy. This dual action, mediated by RE, helps protect skin cells from oxidative damage and senescence while maintaining proteostasis, skin integrity, and cellular proliferation under pollution-induced stress (BAP + UV-A). These findings highlight the potential in mitigating age-related skin changes through the modulation of longevity pathways. Full article

The aging population is steadily increasing, with aging and age-related diseases serving as major risk factors for morbidity, mortality, and economic burden. Peanuts, known as the “longevity nut” in China, have been shown to offer various health benefits, with peanut skin extract (PSE) emerging as a key compound of interest. This study investigates the bioactive compound in PSE with anti-aging potential and explores its underlying mechanisms of action. Procyanidin A1 (PC A1) was isolated from PSE, guided by the K6001 yeast replicative lifespan model. PC A1 prolonged the replicative lifespan of yeast and the yeast-like chronological lifespan of PC12 cells. To further confirm its anti-aging effect, cellular senescence, a hallmark of aging, was assessed. In senescent cells induced by etoposide (Etop), PC A1 alleviated senescence by reducing ROS levels, decreasing the percentage of senescent cells, and restoring proliferative capacity. Transcriptomics analysis revealed that PC A1 induced apoptosis, reduced senescence-associated secretory phenotype (SASP) factors, and modulated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. The antioxidative capacity of PC A1 was also evaluated, showing enhanced resistance to oxidative stress in PC12 cells by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) activity. Moreover, PC A1 induced autophagy, as evidenced by an increase in fluorescence-labeled autophagic compartments and confirmation via Western blot analysis of autophagy-related proteins. In addition, the treatment of an autophagy inhibitor abolished the antioxidative stress and senescence-alleviating effects of PC A1. These findings reveal that PC A1 extended lifespans and alleviated cellular senescence by enhancing oxidative stress resistance and inducing autophagy, positioning it as a promising candidate for further exploration as a geroprotective agent. Full article

Epigenetic mechanisms are central to the regulation of all biological processes. This manuscript reviews the current understanding of diverse epigenetic modifications and their role in the establishment and maintenance of normal skin functions. In healthy skin, these mechanisms allow for the precise control of gene expression, facilitating the dynamic balance between cell proliferation and differentiation necessary for effective barrier function. Furthermore, as the skin ages, alterations in epigenetic marks can lead to impaired regenerative capacity and increased susceptibility to environmental stressors. The interaction between skin microbiota and epigenetic regulation will also be explored, highlighting how microbial communities can influence skin health by modulating the host gene expression. Future research should focus on the development of targeted interventions to promote skin development, resilience, and longevity, even in an ever-changing environment. This underscores the need for integrative approaches to study these complex regulatory networks. Full article

Background and Objectives: The history of facial fillers is very broad, ranging from the use of various materials to modern technologies. Although procedures are considered safe, complications such as skin inflammation, infection, necrosis, or swelling may occur. It is crucial for specialists to be adequately prepared, inform patients how to prepare for corrective procedures, adhere to high safety standards, and continually educate. The goal of this systematic review is to identify complications arising during facial wrinkle correction procedures, as well as to explore safety and potential prevention strategies. Materials and methods: The review of the scientific literature followed the PRISMA guidelines. The search was performed in a single scientific database: PubMed. Considering predefined inclusion and exclusion criteria, articles evaluating the safety of dermal fillers used for facial wrinkle correction, complications, and treatment outcomes were selected. The chosen articles were published from 15 February 2019 to 15 February 2024 (last search date: 25 February 2024). The selected articles compared the complications, product safety, and result longevity of various dermal fillers used for facial wrinkle correction. Results: In thirty-eight articles, which involved 3967 participants, a total of 8795 complications were reported. The majority of complications occurred after injections into the chin and surrounding area (n = 2852). Others were reported in lips and the surrounding area (n = 1911) and cheeks and the surrounding area (n = 1077). Out of the 8795 complications, 1076 were adverse events (AE), including two severe AE cases: mild skin necrosis (n = 1) and abscess (n = 1). There were no cases of vascular occlusion, visual impairment, or deaths related to the performed procedures. A total of 7719 injection site reactions were classified as mild or temporary, such as swelling (n = 1184), sensitivity (n = 1145), pain (n = 1064), bleeding (n = 969), hardening/stiffness (n = 888), nodules/irregularities (n = 849), and erythema (redness) (n = 785). Conclusions: Facial wrinkle correction procedures are generally safe and effective and the results can last from 6 to 24 months, depending on the dermal filler material and its components used. The most common complications after dermal filler injection usually resolve spontaneously, but if they persist, various pharmacological treatment methods can be used according to the condition, and surgical intervention is generally not required. Full article

Background: Urolithin A (Uro-A), a type of polyphenol derived from pomegranate, is known to improve memory function when ingested, in addition to its direct effect on the skin epidermal cells through the activation of longevity gene SIRT1. However, the molI ecular mechanism by which orally ingested Uro-A inhibits cognitive decline via the intestine remains unexplored. Objectives: This study aimed to evaluate the role of Uro-A in improving cognitive function via improved intestinal function and the effect of Uro-A on the inflammation levels and gene expression in hippocampus. Methods: Research to clarify the molecular basis of the functionality of Uro-A was also conducted. Results: The results demonstrated that Uro-A suppressed age-related memory impairment in Aged mice (C57BL/6J Jcl, male, 83 weeks old) by reducing inflammation and altering hippocampal gene expression. Furthermore, exosomes derived from intestinal cells treated with Uro-A and from the serum of Aged mice fed with Uro-A both activated neuronal cells, suggesting that exosomes are promising candidates as mediators of the Uro-A-induced activation of gut–brain interactions. Additionally, neurotrophic factors secreted from intestinal cells may contribute to the Uro-A-induced activation of gut–brain interactions. Conclusions: This study suggests that Uro-A suppresses age-related cognitive decline and that exosomes and other secreted factors may contribute to the activation of the gut–brain interaction. These findings provide new insights into the therapeutic potential of Uro-A for cognitive health. Full article

Skin aging is a complex, multifaceted process influenced by both intrinsic and extrinsic factors. Understanding the molecular mechanisms underlying skin aging is crucial for developing effective anti-aging strategies. Dermal stem cells play a pivotal role in maintaining skin homeostasis, but their functionality is compromised with aging. This study investigated the impact of aging on dermal stem cells and explored the potential of natural extracts in modulating their biological characteristics. Using bulk RNA barcoding and sequencing (BRB-seq), we identified differentially expressed genes (DEGs) between young and aged dermal stem cells, revealing alterations in cellular processes, including cell proliferation, ECM synthesis, and RNA splicing. We also demonstrated that a natural extract, comprising callus cells and Alpine rose leaf extracts, influenced RNA splicing in aged dermal stem cells, leading to improved dermal structure and integrity in vitro. Our findings suggest that natural extracts may exert their effects through senolytic activity and the modulation of RNA splicing, a process crucial to gene expression and cellular function. This study underscores the potential of integrating high-throughput transcriptomics in understanding skin aging, presenting new avenues for the development of innovative, sustainable, and effective anti-aging strategies. Full article

Background: Nutrition, cooking, and gardening lessons individually and together have been shown to increase fruit and vegetable (FV) consumption in school-aged children. The CATCH Rainbow program incorporated nutrition education, cooking, and gardening lessons aimed at increasing FV consumption in elementary school-aged children and assessed changes in participants’ BMI, self-reported FV consumption, and skin carotenoid levels at baseline and post-intervention. Methods: Two-hundred and twenty-five 4th and 5th graders (mean age: 9.8 years and 52% male participants) at Genoa Elementary School participated in six cooking and six gardening sessions between September 2021 and May 2022. Each nutrition education session was 25 min long, paired with either hands-on cooking activities or gardening skills. At baseline and post-intervention, participants’ height and weight were assessed with a stadiometer/scale, and skin carotenoid measurement was taken by a Veggie Meter^® (Longevity Link Corporation (Salt Lake City, UT, USA)). Students also completed the Block Food Frequency Questionnaire to self-report FV consumption at both time points. Focus groups were conducted with children at the end of the program for qualitative feedback. Results: paired samples T-test and regression analysis results indicate no significant decrease in BMI or significant increase in skin carotenoid scores from pre- to post-intervention. However, though not significant, there was an increase in self-reported FV intake by 0.4 servings. Additionally, the qualitative feedback was positive, as children mentioned benefits of healthy eating and expressed enjoyment for growing, cooking, and tasting fruits and vegetables. Conclusions: Results from this study can be used to guide future cooking and gardening programs for elementary school children. Time of the year when implementing these programs and collecting data may impact study outcomes due to seasonal variations in fruit and vegetable intake. Full article

Hyaluronic acid (HA) fillers are extensively utilized in aesthetic medicine due to their biocompatibility, reversibility, and effectiveness in enhancing skin hydration, volume, and overall appearance. These fillers are predominantly produced through microbial fermentation, followed by a critical cross-linking process that enhances their longevity by resisting enzymatic degradation. This review provides a thorough examination of the manufacturing processes that differentiate HA fillers, with particular attention to the distinctions between biphasic and monophasic variants. Unlike previous studies, this review emphasizes the specific cross-linking techniques and their substantial impact on the fillers’ rheological properties, such as elasticity and cohesiveness, which are crucial to their clinical performance and patient outcomes. Additionally, the review offers a comprehensive comparison of HA fillers with non-HA alternatives, including calcium hydroxylapatite, poly-l-lactic acid, and polymethyl methacrylate, highlighting the unique advantages and potential complications associated with each type. By presenting novel insights into the latest advancements and challenges in filler technology, this review aims to provide clinicians with a deeper understanding of filler properties, thereby guiding them in making informed decisions to optimize patient safety and aesthetic results. Full article