Evaluation of Biotechnological Active Peptides Secreted by Saccharomyces cerevisiae with Potential Skin Benefits.

Biotechnological active peptides are gaining interest in the cosmetics industry due to their antimicrobial, anti-inflammatory, antioxidant, and anti-collagenase (ACE) effects, as well as wound healing properties, making them suitable for cosmetic formulations. The antimicrobial activity of peptides (2-10 kDa) secreted by Saccharomyces cerevisiae Ethanol-Red was evaluated against dermal pathogens using broth microdilution and challenge tests. ACE was assessed using a collagenase activity colorimetric assay, antioxidant activity via spectrophotometric monitoring of nitrotetrazolium blue chloride (NBT) reduction, and anti-inflammatory effects by quantifying TNF-α mRNA in lipopolysaccharides (LPS)-exposed dermal fibroblasts. Wound healing assays involved human fibroblasts, endothelial cells, and dermal keratinocytes. The peptides (2-10 kDa) exhibited antimicrobial activity against 10 dermal pathogens, with the Minimum Inhibitory Concentrations (MICs) ranging from 125 µg/mL for Staphylococcus aureus to 1000 µg/mL for Candida albicans and Streptococcus pyogenes. In the challenge test, peptides at their MICs reduced microbial counts significantly, fulfilling ISO 11930:2019 standards, except against Aspergillus brasiliensis. The peptides combined with MicrocareⓇ SB showed synergy, particularly against C. albicans and A. brasilensis. In vitro, the peptides inhibited collagenase activity by 41.8% and 94.5% at 250 and 1000 µg/mL, respectively, and demonstrated antioxidant capacity. Pre-incubation with peptides decreased TNF-α expression in fibroblasts, indicating anti-inflammatory effects. The peptides do not show to promote or inhibit the angiogenesis of endothelial cells, but are able to attenuate fibrosis, scar formation, and chronic inflammation during the final phases of the wound healing process. The peptides showed antimicrobial, antioxidant, ACE, and anti-inflammatory properties, highlighting their potential as multifunctional bioactive ingredients in skincare, warranting further optimization and exploration in cosmetic applications.

Clerodendranthus spicatus (Thunb.) Water Extracts Reduce Lipid Accumulation and Oxidative Stress in the Caenorhabditis elegans.

Clerodendranthus spicatus (Thunb.) (Kidney tea) is a very distinctive ethnic herbal medicine in China. Its leaves are widely used as a healthy tea. Many previous studies have demonstrated its various longevity-promoting effects; however, the safety and specific health-promoting effects of Clerodendranthus spicatus (C. spicatus) as a dietary supplement remain unclear. In order to understand the effect of C. spicatus on the longevity of Caenorhabditis elegans (C. elegans), we evaluated its role in C. elegans; C. spicatus water extracts (CSw) were analyzed for the major components and the effects on C. elegans were investigated from physiological and biochemical to molecular levels; CSw contain significant phenolic components (primarily rosmarinic acid and eugenolinic acid) and flavonoids (primarily quercetin and isorhamnetin) and can increase the lifespan of C. elegans. Further investigations showed that CSw modulate stress resistance and lipid metabolism through influencing DAF-16/FoxO (DAF-16), Heat shock factor 1 (HSF-1), and Nuclear Hormone Receptor-49 (NHR-49) signalling pathways; CSw can improve the antioxidant and hypolipidemic activity of C. elegans and prolong the lifespan of C. elegans (with the best effect at low concentrations). Therefore, the recommended daily use of C. spicatus should be considered when consuming it as a healthy tea on a daily basis.

Evaluating the Dermatological Benefits of Snowberry (Symphoricarpos albus): A Comparative Analysis of Extracts and Fermented Products from Different Plant Parts.

Skin ageing is influenced by both intrinsic and extrinsic factors, with excessive ultraviolet (UV) exposure being a significant contributor. Such exposure can lead to moisture loss, sagging, increased wrinkling, and decreased skin elasticity. Prolonged UV exposure negatively impacts the extracellular matrix by reducing collagen, hyaluronic acid, and aquaporin 3 (AQP-3) levels. Fermentation, which involves microorganisms, can produce and transform beneficial substances for human health. Natural product fermentation using lactic acid bacteria have demonstrated antioxidant, anti-inflammatory, antibacterial, whitening, and anti-wrinkle properties. Snowberry, traditionally used as an antiemetic, purgative, and anti-inflammatory agent, is now also used as an immune stimulant and for treating digestive disorders and colds. However, research on the skin benefits of Fermented Snowberry Extracts remains limited. Thus, we aimed to evaluate the skin benefits of snowberry by investigating its moisturising and anti-wrinkle effects, comparing extracts from different parts of the snowberry plant with those subjected to fermentation using Lactobacillus plantarum. Chlorophyll-free extracts were prepared from various parts of the snowberry plant, and ferments were created using Lactobacillus plantarum. The extracts and ferments were analysed using high-performance liquid chromatography (HPLC) to determine and compare their chemical compositions. Moisturising and anti-ageing tests were conducted to assess the efficacy of the extracts and ferments on the skin. The gallic acid content remained unchanged across all parts of the snowberry before and after fermentation. However, Fermented Snowberry Leaf Extracts exhibited a slight decrease in chlorogenic acid content but a significant increase in ferulic acid content. The Fermented Snowberry Fruit Extract demonstrated increased chlorogenic acid and a notable rise in ferulic acid compared to its non-fermented counterpart. Skin efficacy tests revealed that Fermented Snowberry Leaf and Fruit Extracts enhanced the expression of AQP-3, HAS-3, and COL1A1. These extracts exhibited distinct phenolic component profiles, indicating potential skin benefits such as improved moisture retention and protection against ageing. These findings suggest that Fermented Snowberry Extracts could be developed into effective skincare products, providing a natural alternative for enhancing skin hydration and reducing signs of ageing.

The effect of degeneration of elastic fibres on loss of elasticity and wrinkle formation.

OBJECTIVE: Skin elasticity, which is vital for a youthful appearance, depends on the elastic fibres in the dermis. However, these fibres deteriorate with ageing, resulting in wrinkles and sagging. Changes that occur in the elastic fibres in living human skin and the relationship between elastic fibres and the state of the skin surface remain unclear. Therefore, it is necessary to verify the relationship between elastic fibres and skin elasticity. In this study, we investigated the association of the elastic fibre structure with skin elasticity and stratum corneum protein content in living human skin. METHODS: Thirty-five female volunteers aged 25-66 years were included in this study. Elastic fibres were observed using a multiphoton scanning laser biomicroscope. Skin elasticity was measured using a Cutometer, and stratum corneum proteins (Heat-shock protein 27 [HSP27] and galectin-7 [Gal-7]) in tape-stripped samples were analysed using an enzyme-linked immunosorbent assay. RESULTS: Elastic fibres exhibited increased curvature and thickness with increased age, with fragmentation observed in women aged >60 years. Elastin scores, which reflect thinness and curvature, were negatively correlated with age, whereas they were positively correlated with R7 elasticity (recovery ability). In individuals aged 20-30 years, higher levels of inflammatory markers (HSP27 and Gal-7) correlated with lower elastin scores; however, this trend was not observed in older participants. CONCLUSION: Elastic fibre deterioration worsened after 40 years of age, and this effect correlated with reduced skin recovery and increased wrinkles. In younger individuals, inflammatory markers affected elastic fibres. These findings can guide anti-ageing strategies that focus on elastic fibre preservation and inflammation control.

OBJECTIF: L'élasticité de la peau, vitale pour un aspect jeune, dépend des fibres élastiques du derme. Cependant, ces fibres se détériorent avec l'âge, ce qui entraîne des rides et un affaissement. Les changements qui se produisent dans les fibres élastiques de la peau humaine vivante et la relation entre les fibres élastiques et l'état de la surface de la peau restent peu clairs. Il est donc nécessaire de vérifier la relation entre les fibres élastiques et l'élasticité de la peau. Dans cette étude, nous avons étudié l'association de la structure des fibres élastiques avec l'élasticité de la peau et la teneur en protéine de la couche cornée dans une peau humaine vivante. MÉTHODES: 35 volontaires de sexe féminin âgés de 25 à 66 ans ont été inclus dans cette étude. Des fibres élastiques ont été observées à l'aide d'un biomicroscope à balayage laser multiphotonique. L'élasticité de la peau a été mesurée à l'aide d'un cutomètre, et les protéines de la couche cornée (les protéines de choc thermique 27 [Heat­shock protein 27, HSP27] et galectine­7 [Gal­7]) dans des échantillons avec bande adhésive ont été analysées à l'aide d'un dosage par la méthode immuno­enzymatique ELISA. RÉSULTATS: Les fibres élastiques présentaient une courbure et une épaisseur accrues avec l'âge, avec une fragmentation observée chez les femmes âgées de >60 ans. Les scores d'élastine, qui reflètent la minceur et la courbure, étaient corrélés négativement avec l'âge, tandis qu'ils étaient corrélés positivement avec l'élasticité de R7 (capacité de récupération). Chez les personnes âgées de 20 à 30 ans, des taux plus élevés de marqueurs inflammatoires (HSP27 et Gal­7) étaient corrélés avec une diminution des scores d'élastine; toutefois, cette tendance n'a pas été observée chez les participants plus âgés. CONCLUSION: La détérioration des fibres élastiques s'est aggravée après l'âge de 40 ans, et cet effet était corrélé à une récupération réduite de la peau et à une augmentation des rides. Chez les personnes plus jeunes, les marqueurs inflammatoires ont affecté les fibres élastiques. Ces résultats peuvent orienter les stratégies anti­âge qui se concentrent sur la préservation des fibres élastiques et le contrôle de l'inflammation.

Advantages of Spray Drying over Freeze Drying: A Comparative Analysis of Lonicera caerulea L. Juice Powders-Matrix Diversity and Bioactive Response.

The study investigated the impact of Lonicera caerulea L. juice matrix modification and drying techniques on powder characteristics. The evaluation encompassed phenolics (514.7-4388.7 mg/100 g dry matter), iridoids (up to 337.5 mg/100 g dry matter), antioxidant and antiglycation capacity, as well as anti-ageing properties of powders produced using maltodextrin, inulin, trehalose, and palatinose with a pioneering role as a carrier. Spray drying proved to be competitive with freeze drying for powder quality. Carrier application influenced the fruit powder properties. Trehalose protected the phenolics in the juice extract products, whereas maltodextrin showed protective effect in the juice powders. The concentrations of iridoids were influenced by the matrix type and drying technique. Antiglycation capacity was more affected by the carrier type in juice powders than in extract products. However, with carrier addition, the latter showed approximately 12-fold higher selectivity for acetylcholinesterase than other samples. Understanding the interplay between matrix composition, drying techniques, and powder properties provides insights for the development of plant-based products with tailored attributes, including potential health-linked properties.

Design and Synthesis of Novel Antioxidant 2-Substituted-5,7,8-Trimethyl-1,4-Benzoxazine Hybrids: Effects on Young and Senescent Fibroblasts.

The exponential growth of the aged population worldwide is followed by an increase in the prevalence of age-related disorders. Oxidative stress plays central role in damage accumulation during ageing and cell senescence. Thus, a major target of today's anti-ageing research has been focused on antioxidants counteracting senescence. In the current work, six novel 5,7,8-trimethyl-1,4-benzoxazine/catechol or resorcinol hybrids were synthesized connected through a methoxymethyl-1,2,3-triazolyl or a 1,2,3-triazoly linker. The compounds were evaluated for their antioxidant capacity in a cell-free system and for their ability to reduce intracellular ROS levels in human skin fibroblasts, both young (early-passage) and senescent. The most efficient compounds were further tested in these cells for their ability to induce the expression of the gene heme oxygenase-1 (ho-1), known to regulate redox homeostasis, and cellular glutathione (GSH) levels. Overall, the two catechol derivatives were found to be more potent than the resorcinol analogues. Furthermore, these two derivatives were shown to act coordinately as radical scavengers, ROS inhibitors, ho-1 gene expression inducers, and GSH enhancers. Interestingly, one of the two catechol derivatives was also found to enhance human skin fibroblast viability. The properties of the synthesized compounds support their potential use in cosmetic applications, especially in products targeting skin ageing.

Evaluation of the Safety of Cosmetic Ingredients and Their Skin Compatibility through In Silico and In Vivo Assessments of a Newly Developed Eye Serum.

The term "risk assessment" is often substituted with "safety assessment", to demonstrate the safe properties of cosmetic ingredients and formulations. With respect to the actual legislative framework, the proper use of in silico evaluation could offer a representative non-animal substitute for the toxicity evaluation of cosmetic ingredients. The in silico assessment needs to be integrated with other lines of proof (in vitro and/or in vivo data) in the form of a complex methodology in order to demonstrate the safety evaluation of cosmetic ingredients/products. The present study aimed to develop and characterize a new cosmetic formulation, designed for the skin care of the periorbital area. Quality control comprising stability, physicochemical, and microbiological evaluation was performed. Another objective of this study was to present a screening model for the safety evaluation of the cosmetic formulation by identifying individual ingredients, and to confirm the skin compatibility based on in vivo evaluation. The results demonstrated the in silico and in vivo safety profile of the cosmetic ingredients used in the present formulation. In silico evaluation, using a novel, specific software applicable for the risk evaluation of ingredients and formulations, showed that the incorporated ingredients were non-mutagenic and non-sensitizing, and considering the margin of safety (MoS), the cosmetic raw materials could be considered safe. Skin compatibility was confirmed by the patch test performed under dermatological control, evidencing the "non-irritating" potential of the developed cosmetic formulation.

Potential of Bioactive Protein and Protein Hydrolysate from Apis mellifera Larvae as Cosmeceutical Active Ingredients for Anti-Skin Aging.

This study aimed to extract bioactive proteins and protein hydrolysates from Apis mellifera larvae and assess their potential application in cosmetics as well as their irritation properties. The larvae were defatted and extracted using various mediums, including DI water, along with 0.5 M aqueous solutions of sodium hydroxide, ascorbic acid, citric acid, and hydrochloric acid. Subsequently, the crude proteins were hydrolyzed using the Alcalase® enzyme. All extracts underwent testing for antioxidant activities via the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) and Griess assays. Anti-aging properties were evaluated in terms of anti-collagenase and anti-hyaluronidase effects. Irritation potential was assessed using the hen's egg chorioallantoic membrane (HET-CAM) test. The results revealed that the sodium hydroxide extraction showed promising outcomes in terms of yield, protein content, and effectiveness in inhibiting hyaluronidase, with the highest inhibition at 78.1 ± 1.5%, comparable to that of oleanolic acid. Conversely, crude protein extracted with ascorbic acid and its hydrolysate showed notable antioxidant and collagenase-inhibitory activities. Remarkably, their anti-collagenase effects were comparable to those of ascorbic acid and lysine. Additionally, it demonstrated safety upon testing with the CAM. In conclusion, the findings provided valuable insights into the utilization of A. mellifera larval proteins as active ingredients with a wide range of cosmeceutical applications, particularly due to their antioxidant, anti-aging, and low irritation properties, which hold significant promise for anti-skin wrinkles.

A Characterization of Biological Activities and Bioactive Phenolics from the Non-Volatile Fraction of the Edible and Medicinal Halophyte Sea Fennel (Crithmum maritimum L.).

Although the biochemical composition and biological properties of the volatile fraction of the halophyte sea fennel (Crithmum maritimum L.) have been largely described, little is known about its polar constituents and bioactivities. Here, a hydromethanolic extract of Crithmum maritimum (L.) leaves was fractionated, and the fractions were evaluated in vitro for antioxidant (using DPPH, ABTS, and FRAP bioassays), anti-inflammatory (inhibition of NO production in RAW 264.7 macrophages), antidiabetic (alpha-glucosidase inhibition), neuroprotective (inhibition of acetylcholinesterase), and skin-protective (tyrosinase and melanogenesis inhibitions) activities. Polar fractions of the extract were rich in phenolics and, correlatively, displayed a strong antioxidant power. Moreover, fractions eluted with MeOH20 and MeOH80 exhibited a marked inhibition of alpha-glucosidase (IC50 = 0.02 and 0.04 mg/mL, respectively), MeOH60 fractions showed a strong capacity to reduce NO production in macrophages (IC50 = 6.4 µg/mL), and MeOH80 and MeOH100 fractions had strong anti-tyrosinase activities (630 mgKAE/gDW). NMR analyses revealed the predominance of chlorogenic acid in MeOH20 fractions, 3,5-dicaffeoylquinic acid in MeOH40 fractions, and 3-O-rutinoside, 3-O-glucoside, 3-O-galactoside, and 3-O-robinobioside derivatives of quercetin in MeOH60 fractions. These compounds likely account for the strong antidiabetic, antioxidant, and anti-inflammatory properties of sea-fennel polar extract, respectively. Overall, our results make sea fennel a valuable source of medicinal or nutraceutical agents to prevent diabetes, inflammation processes, and oxidative damage.

Topical application of retinyl propionate, 4 hexyl resorcinol, and niacinamide reverses molecular and clinical features of ageing.

OBJECTIVE: Topical tretinoin is the mainstay of treatment for photoageing, despite the risk of skin irritation. Cosmetic combination anti-ageing formulations may offer similar efficacy to tretinoin, while improving on tolerability. We aim to demonstrate facial appearance benefits of a novel triple-active cosmetic formulation containing 4-hexylresorcinol, retinyl propionate, and niacinamide and to identify transcriptomic biomarkers underpinning these benefits. METHODS: A cosmetic prototype formulation containing 4-hexylresorcinol, retinyl propionate, and niacinamide was evaluated ex vivo and in a clinical study. For ex vivo experiments, the cosmetic formulation was applied for 3 days to healthy surgical discard skin from female donors aged 31-51 years, with tissues harvested for gene expression and histologic analyses. In the clinical study, females aged 47-66 years with moderate-to-severe overall visual photodamage on the face applied either topical 0.02% tretinoin or the cosmetic formulation to the face for 16 weeks and to forearms for 1 week, with forearm biopsies taken for gene expression analyses. Visual grading for facial photodamage and VISIA-CR images was taken throughout the clinical study. Safety was visually assessed during site visits, and adverse event monitoring was conducted throughout. RESULTS: Gene expression analyses in both studies revealed modulation of pathways associated with skin rejuvenation, with several genes of interest identified due to being implicated in ageing and differentially expressed following the application of the cosmetic formulation. Reversal of a consensus skin ageing gene signature was observed with the cosmetic formulation and tretinoin in the ex vivo and clinical studies. Both the cosmetic formulation and tretinoin clinically improved the overall appearance of photoageing, crow's feet, lines, wrinkles, and pores. Adverse event reporting showed that the cosmetic formulation caused less skin irritation than tretinoin. CONCLUSION: In a double-blind clinical study, the novel triple-active cosmetic combination formulation improved the visual appearance of photoageing similarly to prescription tretinoin. The cosmetic formulation and tretinoin reversed a consensus gene signature associated with ageing. Together with adverse event reporting, these results suggest that the cosmetic formulation may be a well-tolerated and efficacious alternative to tretinoin for improving the visual features of photoageing.

OBJECTIF: Le trétinoine topique est le pilier du traitement du photovieillissement, malgré le risque d'irritation cutanée. Les formulations cosmétiques combinés anti­âge peuvent offrir une efficacité similaire à la trétinoine, tout en améliorant la tolérance. Notre objectif est de démontrer les avantages esthétiques pour l'apparence du visage d'une nouvelle formulation cosmétique triple active contenant du 4­hexylrésorcinol, du rétinyl propionate et de la niacinamide, et d'identifier les biomarqueurs transcriptomiques sous­jacents à ces avantages. MÉTHODES: Une formulation cosmétique prototype contenant du 4­hexylrésorcinol, du rétinyl propionate et de la niacinamide a été évaluée ex vivo et lors d'une étude clinique. Pour les expériences ex vivo, la formulation cosmétique a été appliquée pendant 3 jours sur des peaux saines issues de donatrices âgées de 31 à 51 ans, avec prélèvement de tissus pour l'analyse de l'expression génique et l'histologie. Dans l'étude clinique, des femmes âgées de 47 à 66 ans présentant un photovieillissement visuel global modéré a sévère sur le visage ont appliqué soit du trétinoine topique à 0.02%, soit la formulation cosmétique sur le visage pendant 16 semaines et sur les avant­bras pendant 1 semaine, avec des biopsies d'avant­bras prélevées pour l'analyse de l'expression génique. L'évaluation visuelle du photovieillissement facial et les images VISIA­CR ont été réalisées tout au long de l'étude clinique. La sécurité a été évaluée visuellement lors des visites sur site, et une surveillance des événements indésirables a été effectuée. RÉSULTATS: Les analyses de l'expression génique dans les deux études ont révélé une modulation des voies associées au rajeunissement cutané, avec plusieurs gènes d'intérêts identifiés en raison de leur implication dans le vieillissement et de leur expression différentielle suite à l'application de la formulation cosmétique. Une inversion de la signature génique du vieillissement cutané consensuelle a été observée avec la formulation cosmétique et la trétinoine dans les études ex vivo et cliniques. La formulation cosmétique et la trétinoine ont toutes deux amélioré cliniquement l'apparence globale du photovieillissement, des pattes d'oie, des ridules, des rides et des pores. Les rapports sur les événements indésirables ont montré que la formulation cosmétique provoquait moins d'irritation cutanée que la trétinoine. CONCLUSION: Dans une étude clinique en double aveugle, la nouvelle formulation cosmétique triple active a amélioré l'apparence visuelle du photovieillissement de manière similaire à la trétinoine sur ordonnance. La formulation cosmétique et la trétinoine ont inversé une signature génique consensuelle associée au vieillissement. En tenant compte des rapports sur les événements indésirables, ces résultats suggèrent que la formulation cosmétique pourrait constituer une alternative bien tolérée et efficace à la trétinoine pour améliorer les caractéristiques visuelles du photovieillissement.

Tricarboxylic Acid Cycle Intermediates and Individual Ageing.

Anti-ageing biology and medicine programmes are a focus of genetics, molecular biology, immunology, endocrinology, nutrition, and therapy. This paper discusses metabolic therapies aimed at prolonging longevity and/or health. Individual components of these effects are postulated to be related to the energy supply by tricarboxylic acid (TCA) cycle intermediates and free radical production processes. This article presents several theories of ageing and clinical descriptions of the top markers of ageing, which define ageing in different categories; additionally, their interactions with age-related changes and diseases related to α-ketoglutarate (AKG) and succinate SC formation and metabolism in pathological states are explained. This review describes convincingly the differences in the mitochondrial characteristics of energy metabolism in animals, with different levels (high and low) of physiological reactivity of functional systems related to the state of different regulatory systems providing oxygen-dependent processes. Much attention is given to the crucial role of AKG and SC in the energy metabolism in cells related to amino acid synthesis, epigenetic regulation, cell stemness, and differentiation, as well as metabolism associated with the development of pathological conditions and, in particular, cancer cells. Another goal was to address the issue of ageing in terms of individual characteristics related to physiological reactivity. This review also demonstrated the role of the Krebs cycle as a key component of cellular energy and ageing, which is closely associated with the development of various age-related pathologies, such as cancer, type 2 diabetes, and cardiovascular or neurodegenerative diseases where the mTOR pathway plays a key role. This article provides postulates of postischaemic phenomena in an ageing organism and demonstrates the dependence of accelerated ageing and age-related pathology on the levels of AKG and SC in studies on different species (roundworm Caenorhabditis elegans, Drosophila, mice, and humans used as models). The findings suggest that this approach may also be useful to show that Krebs cycle metabolites may be involved in age-related abnormalities of the mitochondrial metabolism and may thus induce epigenetic reprogramming that contributes to the senile phenotype and degenerative diseases. The metabolism of these compounds is particularly important when considering ageing mechanisms connected with different levels of initial physiological reactivity and able to initiate individual programmed ageing, depending on the intensity of oxygen consumption, metabolic peculiarities, and behavioural reactions.

SSK1-Loaded Neurotransmitter-Derived Nanoparticles for Alzheimer's Disease Therapy via Clearance of Senescent Cells.

Age is a significant contributor to the onset of AD. Senolysis has been recently demonstrated to ameliorate aging-associated diseases that showing a great potential in AD therapy. However, due to the presence of BBB, the anti-AD activity of senolytics are significantly diminished. SSK1 is a prodrug that can be activated by ß-gal, a lysosomal enzyme commonly upregulated in senescent cells, and thus selectively eliminates senescent cells. Furthermore, the level of ß-gal is significantly correlated with conventional AD genes from clinical sequencing data. SSK1-loaded neurotransmitter -derived lipid nanoparticles are herein developed (SSK1-NPs) that revealing good BBB penetration and bioavailability of in the body. At the brain lesion, SSK1-NP treatment significantly reduces the expression of genes associated with senescence, induced senescent cells elimination, decreased amyloid-beta accumulation, and eventually improve cognitive function of aged AD mice. SSK1-NPs, a novel nanomedicine displaying potent anti-AD activity and excellent safety profile, provides a promising strategy for AD therapy.

Comparisons between eyebags, droopy eyelids, and eyebrow positioning identified by photo-numeric scales or identified by written descriptive scales: Insights from the Singapore/Malaysia cross-sectional genetics epidemiology study (SMCGES) cohort.

BACKGROUND: We evaluate skin sagging phenotypes (eyebags, droopy eyelids, low eyebrow positioning) using written descriptive scales and photo-numeric scales. We also study how anti-ageing interventions and digital screen time influence skin sagging. AIM: We compare the two phenotype assessment methods with each other. METHOD: Skin sagging and personal lifestyle data obtained from 2885 ethnic Chinese young adults from the Singapore/Malaysia cross-sectional genetics epidemiology study (SMCGES) cohort were collated and compared. RESULTS: Significant correlations (p-value < 0.001) between written descriptive scales and photo-numeric scales were observed for eyebags (0.25) and eyebrow positioning (0.08). Significant correlations (p-value < 0.001) were observed after combining both scales for eyebags (0.38), droopy eyelids (0.30), and eyebrow positioning (0.30). Anti-ageing interventions are associated with delayed progression of eyebags from 18-45 years old, droopy eyelids from 31-45 years old, and eyebrow positioning from 35-40 years old. Significantly lower (p-value < 0.02) eyebrow positioning is associated with both <1 and 1-3 h of screen time stratified by age. CONCLUSION: Written descriptive scales provide comparable results to photo-numeric scales. However, validating and adapting photo-numeric scales for different populations identifies phenotypes better. Anti-ageing interventions are beneficial at different age ranges. Screen time is associated with skin sagging in young (18-30 years old) participants.

The Potential Use of Vitamin D3 and Phytochemicals for Their Anti-Ageing Effects.

Unlike other vitamins, vitamin D3 is synthesised in skin cells in the body. Vitamin D3 has been known as a bone-related hormone. Recently, however, it has been considered as an immune vitamin. Vitamin D3 deficiency influences the onset of a variety of diseases. Vitamin D3 regulates the production of proinflammatory cytokines such as tumour necrosis factor-α (TNF-α) through binding to vitamin D receptors (VDRs) in immune cells. Since blood levels of vitamin D3 (25-OH-D3) were low in coronavirus disease 2019 (COVID-19) patients, there has been growing interest in the importance of vitamin D3 to maintaining a healthy condition. On the other hand, phytochemicals are compounds derived from plants with over 7000 varieties and have various biological activities. They mainly have health-promoting effects and are classified as terpenoids, carotenoids, flavonoids, etc. Flavonoids are known as the anti-inflammatory compounds that control TNF-α production. Chronic inflammation is induced by the continuous production of TNF-α and is the fundamental cause of diseases like obesity, dyslipidaemia, diabetes, heart and brain diseases, autoimmune diseases, Alzheimer's disease, and cancer. In addition, the ageing process is induced by chronic inflammation. This review explains the cooperative effects of vitamin D3 and phytochemicals in the suppression of inflammatory responses, how it balances the natural immune response, and its link to anti-ageing effects. In addition, vitamin D3 and phytochemicals synergistically contribute to anti-ageing by working with ageing-related genes. Furthermore, prevention of ageing processes induced by the chronic inflammation requires the maintenance of healthy gut microbiota, which is related to daily dietary habits. In this regard, supplementation of vitamin D3 and phytochemicals plays an important role. Recently, the association of the prevention of the non-disease condition called "ME-BYO" with the maintenance of a healthy condition has been an attractive regimen, and the anti-ageing effect discussed here is important for a healthy and long life.

The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing.

Ageing is a crucial risk factor for Alzheimer's disease (AD) and is characterised by systemic changes in both intracellular and extracellular microenvironments that affect the entire body instead of a single organ. Understanding the specific mechanisms underlying the role of ageing in disease development can facilitate the treatment of ageing-related diseases, such as AD. Signs of brain ageing have been observed in both AD patients and animal models. Alleviating the pathological changes caused by brain ageing can dramatically ameliorate the amyloid beta- and tau-induced neuropathological and memory impairments, indicating that ageing plays a crucial role in the pathophysiological process of AD. In this review, we summarize the impact of several age-related factors on AD and propose that preventing pathological changes caused by brain ageing is a promising strategy for improving cognitive health.

A study of anti-wrinkle functions and improvement of cream with Phaseolus angularis.

Chronic exposure to ultraviolet (UV) radiation from sunlight accelerates skin ageing, which is followed by harsh, thick, dry and loose conditions. One of the most demonstrative symptoms is deep wrinkles induced by skin barrier disruption. Our previous research showed that Phaseolus angularis seed extract (PASE) effectively inhibits skin ageing through UVB protection in HaCaT cells by suppressing skin damage. However, its efficacy has not been evaluated in clinical trials so far. PASE cream's effectiveness was initially tested on the artificial skin model, revealing an increase in filaggrin and defence against skin damage. Based on these results, in this single-centred, randomized, double-blind study, we investigated the anti-ageing effect of PASE in human eye wrinkle areas. For these 21 healthy adult women aged 30 to 59, a PASE cream was applied to the right eye wrinkle area and a placebo to the left eye wrinkle area twice a day (morning and evening) for 12 weeks. The change in thick, deep crease wrinkles around the eyes was confirmed by visual evaluation, skin measurements and a questionnaire. As a result, the surface roughness (R1), maximum roughness (R2), average roughness (R3), smoothness depth (R4) and arithmetic mean roughness (R5) values in the group using the PASE cream all decreased. Particularly, R1, R4 and R5 significantly decreased by 18.1%, 18.6% and 25.0%, respectively. Subjects who applied PASE cream also experienced an improvement in skin moisture nearly twice the time compared to the placebo group. In addition, no participants reported side effects. Our study showed that PASE cream led to clinically significant levels of wrinkle improvement. In conclusion, as PASE is a natural, safe food with no side effects, it can be a good resource for natural anti-wrinkle functional cosmetics in the future.

L'exposition chronique aux rayons ultraviolets (UV) du soleil accélère le vieillissement cutané, qui provoque un épaississement et un assèchement de la peau et la rend plus lâche. La présence de rides profondes induites par la rupture de la barrière cutanée en constitue l'un des symptômes les plus manifestes. Lors d'études précédentes, nous nous sommes rendu compte que l'extrait de graines de Phaseolus angularis (PASE) inhibait efficacement le vieillissement de la peau en assurant la protection anti­UVB des cellules HaCaT grâce à la suppression des lésions cutanées. Cependant, son efficacité n'a pas été évaluée lors d'essais cliniques à ce jour. L'efficacité de la crème PASE a d'abord été testée sur le modèle de peau artificielle, sur laquelle elle a fait augmenter les taux de filaggrine et assuré une défense contre les lésions cutanées. Sur la base de ces résultats, dans cette étude unicentrique, randomisée et en double aveugle, nous avons étudié l'effet anti­âge de la PASE chez l'humain au niveau des rides proches de l'œil. Pour ces 21 femmes adultes en bonne santé âgées de 30 à 59 ans, une crème PASE a été appliquée sur la zone de rides de l'œil droit et un placebo sur la zone de rides de l'œil gauche deux fois par jour (matin et soir) pendant 12 semaines. La modification des rides profondes et épaisses autour des yeux a été confirmée par une évaluation visuelle, des mesures cutanées et un questionnaire. Il a été découvert que les valeurs de rugosité de surface (R1), de rugosité maximale (R2), de rugosité moyenne (R3), de profondeur de douceur (R4) et de moyenne arithmétique (R5) dans le groupe à l'aide de la crème PASE avaient toutes diminué. En particulier, R1, R4 et R5 ont significativement diminué de 18,1 %, de 18,6 % et de 25,0 %, respectivement. Les patients qui ont appliqué la crème PASE ont également présenté une amélioration de l'hydratation de la peau presque deux fois supérieure à celle du groupe placebo. En outre, aucun participant n'a signalé d'effets secondaires. Notre étude a montré que la crème PASE entraînait des niveaux cliniquement significatifs d'amélioration des rides. En conclusion, comme le PASE est un aliment naturel, sûr et dépourvu d'effets secondaires, elle peut constituer une bonne ressource pour les cosmétiques fonctionnels naturels antirides à l'avenir.

Transcriptomic and metabolomic analyses reveal that lemon extract prolongs Drosophila lifespan by affecting metabolism.

Ageing is an evolutionarily conserved and irreversible biological process in different species. Numerous studies have reported that taking medicine is an effective approach to slow ageing. Lemon extract (LE) is a natural extract of lemon fruit that contains a variety of bioactive phytochemicals. Various forms of LE have been shown to play a role in anti-ageing and improving ageing-related diseases. However, studies on the molecular mechanism of LE in Drosophila ageing have not been reported. In this study, we found that 0.05 g/L LE could significantly extend Drosophila lifespan and greatly improve antioxidative and anti-heat stress abilities. Furthermore, transcriptome and metabolome analyses of 10 d flies between the LE-fed and control groups suggested that the differentially expressed gene ppo1 (Prophenoloxidase 1) and metabolite L-DOPA (Levodopa) were co-enriched in the tyrosine metabolism pathway. Overall, our results indicate that affecting metabolism was the main reason for LE extending Drosophila lifespan.

N-acetyl-L-hydroxyproline - A potent skin anti-ageing active preventing advanced glycation end-product formation in vitro and ex vivo.

OBJECTIVE: Advanced glycation end-products (AGEs) represent a large group of compounds generated by a non-enzymatic reaction between reducing sugars and amino groups. The formation and accumulation of AGEs in the skin lead to protein crosslinking, dermal stiffening and yellowing, which ultimately contribute to cutaneous ageing. Amino acids have been described to exhibit anti-glycation effects. The objective of this study was to understand the inhibitory role of the amino acid derivative N-acetyl-L-hydroxyproline (NAHP) as an anti-glycation active for human skin. METHODS: A cell-free assay investigating the inhibition of glycation of serum albumin by NAHP was used to determine the capability of NAHP to decrease AGE formation. Also, by assessing the amount of the AGE N-(carboxymethyl)lysine (CML) the anti-glycation abilities of NAHP were investigated utilizing dot blot analysis. The improvement of cell-matrix interaction by NAHP was determined in vitro using a glycated fibroblast-populated collagen lattice (FPCL) dermis model. In skin biopsies, AGE autofluorescence was determined after treatment with NAHP and/or glucose ex vivo. RESULTS: NAHP significantly and dose-dependently inhibited levels of AGEs, which were induced by the glycation of a protein solution. This decrease could be visualized by showing that the brownish appearance as well as the AGE-specific fluorescence of glucose-treated samples were reduced after the application of increasing amounts of NAHP. Also, CML formation was dose-dependently inhibited by NAHP. In FPCLs, the contractile capacity of fibroblasts was significantly disturbed after glycation. This could be prevented by the addition of NAHP. Compared to glyoxal-treated samples, the co-application of NAHP significantly decreased the diameter as well as the weight of glycated FPCLs. Ex vivo application of glucose to skin explants showed a higher AGE fluorescence signal compared to control explants. Co-treatment with NAHP and glucose decreased the level of AGE fluorescence in comparison to glucose-treated explants. CONCLUSION: These data provide clear evidence that under glycation stress conditions treatment with NAHP inhibited AGE formation in vitro and ex vivo and prevented the loss of cellular contractile forces in a glycated dermis model. Thus, NAHP obviously provides a beneficial treatment option to counteract AGE-related changes in human skin such as dermal stiffening and yellowish skin appearance.

OBJECTIF: Les produits finis de glycation avancée (AGE) représentent un grand groupe de composés générés par une réaction non enzymatique entre des sucres réduits et des groupes amino. La formation et l'accumulation d'AGE dans la peau entraînent une réticulation protéique, un raidissement de la peau et un jaunissement, qui finissent par contribuer au vieillissement cutané. Les acides aminés ont été décrits comme ayant des effets d'anti­glycation. L'objectif de cette étude était de comprendre le rôle inhibiteur du dérivé d'acide aminé N­acétyl­L­hydroxyproline (NAHP) en tant qu'actif anti­glycation pour la peau humaine. MÉTHODES: Un test acellulaire étudiant l'inhibition de la glycation de l'albumine sérique par la NAHP a été utilisé pour déterminer la capacité de la NAHP à diminuer la formation d'AGE. En évaluant la quantité de l'AGE N­(carboxyméthyl)lysine (CML), les capacités d'anti­glycation de la NAHP ont également été étudiées à l'aide d'une analyse par dot blot. L'amélioration de l'interaction cellule­matrice par la NAHP a été déterminée in vitro à l'aide d'un modèle de derme de lattices de collagène composées de fibroblastes glyqués. Dans des biopsies cutanées, l'autofluorescence des AGE a été déterminée après un traitement par NAHP et/ou glucose ex vivo. RÉSULTATS: La NAHP a inhibé de manière significative et dose­dépendante les taux d'AGE induits par la glycation d'une solution protéique. Cette diminution a pu être visualisée en montrant que l'aspect brunâtre ainsi que la fluorescence spécifique aux AGE des échantillons traités par glucose ont été réduits après l'application de quantités croissantes de NAHP. En outre, la formation de CML était inhibée de manière dose­dépendante par la NAHP. Dans des lattices de collagène composées de fibroblastes, la capacité contractile des fibroblastes était significativement perturbée après la glycation. Cela a pu être évité par l'ajout de NAHP. Par rapport aux échantillons traités au glyoxal, la co­application de NAHP a significativement réduit le diamètre ainsi que le poids des lattices de collagène composées de fibroblastes glyquées. L'application ex vivo de glucose sur les explants de peau a montré un signal de fluorescence des AGE plus élevé que les explants témoins. Le traitement concomitant par NAHP et glucose a réduit le niveau de fluorescence des AGE par rapport aux explants traités par glucose. CONCLUSION: Ces données fournissent des preuves évidentes que, dans des conditions de stress par glycation, le traitement par NAHP a inhibé la formation d'AGE in vitro et ex vivo, et a prévenu la perte des forces contractiles cellulaires dans un modèle de derme glyqué. Ainsi, la NAHP constitue manifestement une option de traitement bénéfique pour contrer les changements liés aux AGE dans la peau humaine, tels que le raidissement du derme et l'aspect jaunâtre de la peau.

Review of optical methods for noninvasive imaging of skin fibroblasts-From in vitro to ex vivo and in vivo visualization.

Fibroblasts are among the most common cell types in the stroma responsible for creating and maintaining the structural organization of the extracellular matrix in the dermis, skin regeneration, and a range of immune responses. Until now, the processes of fibroblast adaptation and functioning in a varying environment have not been fully understood. Modern laser microscopes are capable of studying fibroblasts in vitro and ex vivo. One-photon- and two-photon-excited fluorescence microscopy, Raman spectroscopy/microspectroscopy are well-suited noninvasive optical methods for fibroblast imaging in vitro and ex vivo. In vivo staining-free fibroblast imaging is not still implemented. The exception is fibroblast imaging in tattooed skin. Although in vivo noninvasive staining-free imaging of fibroblasts in the skin has not yet been implemented, it is expected in the future. This review summarizes the state-of-the-art in fibroblast visualization using optical methods and discusses the advantages, limitations, and prospects for future noninvasive imaging.

Combatting ageing in dermal papilla cells and promoting hair follicle regeneration using exosomes from human hair follicle dermal sheath cup cells.

Dermal papilla cells (DPCs) undergo premature ageing in androgenetic alopecia and senescent alopecia. As critical components of hair follicle reconstruction, DPCs are also prone to senescence in vitro, resulting in a diminished hair follicle inductivity capacity. Dermal sheath cup cells (DSCCs), a specific subset of hair follicle mesenchymal stem cells, intimately linked to the function of DPCs. The primary objective of this research is to investigate the anti-ageing effect of exosomes derived from DSCCs (ExoDSCCs ) on DPCs. Exosomes were utilized to treat H2 O2 -induced DPCs or long-generation DPCs(P10). Our findings demonstrate that ExoDSCCs(P3) promote the proliferation, viability and migration of senescent DPCs while inhibiting cell apoptosis. The expression of senescence marker SA-ß-Gal were significantly downregulated in senescent DPCs. When treated with ExoDSCCs(P3) , expression of inducibility related markers alkaline phosphatase and Versican were significantly upregulated. Additionally, ExoDSCCs(P3) activated the Wnt/ß-catenin signalling in vitro. In patch assay, ExoDSCCs(P3) significantly promoted hair follicle reconstruction in senescent DPCs. In summary, our work highlights that ExoDSCCs(P3) may restore the biological functions and improve the hair follicle induction ability of senescent DPCs. Therefore, ExoDSCCs(P3) may represent a new strategy for intervening in the ageing process of DPCs, contributing to the prevention of senile alopecia.