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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Long-term dietary DHA intervention prevents telomere attrition and lipid disturbance in telomerase-deficient male mice.

PURPOSE: Previous evidence indicated anti-ageing potential of docosahexaenoic acid (DHA), but the underlying mechanism remains unclear. We investigated protective effect of DHA on telomere attrition and lipid disturbance in male mice with premature ageing caused by telomerase deficiency. METHODS: Wild-type (WT) and fourth-generation telomerase-deficient (G4 Terc-/-, Terc knockout, KO) male mice (C57BL/6, 2 months old) were fed control diet (WT-C and KO-C groups) or DHA-enriched diet containing 0.80% DHA by weight (WT-DHA and KO-DHA groups) for 10 months. The ageing phenotypes and metabolic level [carbon dioxide emission, oxygen consumption, and respiratory exchange ratio (RER)] were assessed at the end of the experiment. Telomere length in various tissues and the hepatic gene and protein expression for regulating lipid synthesis and lipolysis were measured. Data were tested using one- or two-factor ANOVA. RESULTS: In KO male mice, DHA prevented weight loss, corrected high RER, and reduced fat loss. Telomere shortening was reduced by 22.3%, 25.5%, and 13.5% in heart, liver, and testes of the KO-DHA group compared with those in the KO-C group. The KO-DHA group exhibited higher gene transcription involved in glycerol-3-phosphate pathway [glycerol-3-phosphate acyltransferase (Gpat)], lower gene expression of ß-oxidation [carnitine palmitoyltransferase 1a (Cpt1a)], and upregulation of proteins in lipid synthesis [mammalian target of rapamycin complex 1 (mTORC1) and sterol responsive element binding protein 1 (SREBP1)] in liver than the KO-C group. CONCLUSION: Long-term DHA intervention attenuates telomere attrition and promotes lipid synthesis via the tuberous sclerosis complex 2 (TSC2)-mTORC1-SREBP1 pathway in KO male mice.

Biotechnological Approaches to Producing Natural Antioxidants: Anti-Ageing and Skin Longevity Prospects.

Plants are the main source of bioactive compounds that can be used for the formulation of cosmetic products. Plant extracts have numerous proven health benefits, among which are anti-ageing and skin-care properties. However, with the increased demand for plant-derived cosmetic products, there is a crucial prerequisite for establishing alternative approaches to conventional methods to ensure sufficient biomass for sustainable production. Plant tissue culture techniques, such as in vitro root cultures, micropropagation, or callogenesis, offer the possibility to produce considerable amounts of bioactive compounds independent of external factors that may influence their production. This production can also be significantly increased with the implementation of other biotechnological approaches such as elicitation, metabolic engineering, precursor and/or nutrient feeding, immobilization, and permeabilization. This work aimed to evaluate the potential of biotechnological tools for producing bioactive compounds, with a focus on bioactive compounds with anti-ageing properties, which can be used for the development of green-label cosmeceutical products. In addition, some examples demonstrating the use of plant tissue culture techniques to produce high-value bioactive ingredients for cosmeceutical applications are also addressed, showing the importance of these tools and approaches for the sustainable production of plant-derived cosmetic products.

Reduction of senescence-associated secretory phenotype and exosome-shuttled miRNAs by Haritaki fruit extract in senescent dermal fibroblasts.

OBJECTIVE: Skin ageing is linked to the accumulation of senescent cells and a "senescence-associated secretory phenotype" (SASP). SASP factors include chemokines, cytokines, and small extracellular vesicles (EVs) containing miRNAs. We characterized SASP profile markers in normal human dermal fibroblasts (HDFs) and evaluated the effect of Haritaki fruit extract on these senescence markers. METHODS: Senescence was induced in HDFs by ionizing radiation (X ray), followed by 14 days of culture. Parallel incubations included fibroblasts treated for 12 days with 10 or 100 µg/mL Haritaki (a standardized extract of Terminalia chebula fruit). Senescence was assessed on Day 14 according to cell morphology, ß-galactosidase activity, RT-qPCR measurement of SASP genes, as well as semi-quantitative (RT-qPCR) expression of miRNAs contained in EVs isolated from the medium. The size and distribution of EVs were measured by Nanoparticle Tracking Analysis. RESULTS: Human dermal fibroblasts exhibited a senescent phenotype 14 days after ionizing-radiation, demonstrated by a flattened and irregular shape, increased ß-galactosidase activity and over-expression of SASP genes. CSF3, CXCL1, IL1ß, IL6 and IL8 genes were increased by 1492%, 1041%, 343%, 478%, 2960% and 293%, respectively. The cell cycle inhibitor, CDKN1A, was increased by 357%, while COL1A1, was decreased by 56% and MMP1 was increased by 293%. NTA analysis of the EVs size distribution indicated a mix of exosomes (45-100 nm) and microvesicles (100-405 nm). miRNA expression in EVs was increased in senescent fibroblasts. miR 29a-3p, miR 30a-3p, miR 34a-5p, miR 24a-3p and miR 186-5p were increased in senescent HDF by 4.17-, 2.43-, 1.17-, 2.01, 12.5-fold, respectively. Incubation of senescent fibroblasts with Haritaki extract strongly decreased SASP mRNA levels and miRNA expression in EVs. CONCLUSION: Haritaki strongly reduced SASP expression and EV-shuttled miRNAs in senescent fibroblasts. These results indicate that Haritaki has strong senomorphic properties and may be a promising ingredient for the development of new anti-ageing dermo-cosmetic products by inhibiting deleterious effects of senescent cells.

OBJECTIF: Le vieillissement cutané est lié à l'accumulation de cellules sénescentes et à un « phénotype sécrétoire associé à la sénescence ¼ (SASP). Le SASP est constitué de chimiokines, cytokines et de petites vésicules extracellulaires (VE) contenant des miARN. Nous avons caractérisé les marqueurs du SASP dans des fibroblastes dermiques humains normaux (HDF) et évalué l'effet d'un extrait de fruit d'Haritaki sur ces marqueurs de la sénescence. MÉTHODES: La sénescence a été induite dans les HDF par des rayonnements ionisants (rayons X), suivis de 14 jours de culture. Parallèlement, des HDF ont été traités pendant 12 jours avec 10 ou 100 µg/mL d'Haritaki (un extrait standardisé de fruit de Terminalia chebula). La sénescence a été évaluée au jour 14 en fonction de la morphologie cellulaire, de l'activité ß-galactosidase, de la mesure des gènes du SASP par RT-PCR, ainsi que de l'expression semi-quantitative (RT-qPCR) des miARN contenus dans les VE isolées du milieu. La taille et la distribution des VE ont été mesurées par Nanoparticle Tracking Analysis (NTA). RÉSULTATS: Les HDF ont présenté un phénotype sénescent 14 jours après le rayonnement ionisant, en effet, ils avaient une forme aplatie et irrégulière, une activité ß-galactosidase accrue et une surexpression des gènes du SASP. Les ARNm de CSF3, CXCL1, IL1ß, IL6 et IL8 ont été augmentés de 1492%, 1041%, 343%, 478%, 2960% et 293%, respectivement. L'inhibiteur du cycle cellulaire, CDKN1A, a été augmenté de 357%, tandis que le COL1A1 a diminué de 56% et la MMP1 a augmenté de 293%. L'analyse NTA de la distribution de taille des VE a montré un mélange d'exosomes (45-100 nm) et de microvésicules (100-405 nm). L'expression des miARN dans les VE a augmenté dans les fibroblastes sénescents. Les miR 29a-3p, miR 30a-3p, miR 34a-5p, miR 24a-3p et miR 186-5p ont été augmentés dans le HDF sénescent de, respectivement, 4,17-, 2,43-, 1,17-, 2,01 et 12,5- fois. L'incubation de fibroblastes sénescents avec l'extrait de Haritaki a fortement diminué les niveaux d'ARNm du SASP et l'expression de miARN dans les VE. CONCLUSION: L'extrait d'Haritaki a fortement réduit l'expression du SASP et de miARN contenus dans les VE des fibroblastes sénescents. Ces résultats indiquent que Haritaki possède de fortes propriétés sénomorphiques et pourrait être un ingrédient prometteur pour le développement de nouveaux produits dermo-cosmétiques anti-âge en inhibant les effets délétères des cellules sénescentes.

Secretomes as an emerging class of bioactive ingredients for enhanced cosmeceutical applications.

Skin ageing is predominantly caused by either intrinsic or extrinsic factors, leading to undesirable skin features. Advancements in both molecular and cellular fields have created possibilities in developing novel stem cell-derived active ingredients for cosmeceutical applications and the beauty industry. Mesenchymal stromal cell (MSC)-derived secretomes or conditioned media hold great promise for advancing skin repair and regeneration due to the presence of varying cytokines. These cytokines signal our cells and trigger biological mechanisms associated with anti-inflammatory, antioxidant, anti-ageing, proliferative and immunomodulatory effects. In this review, we discuss the potential of MSC secretomes as novel biomaterials for skincare and rejuvenation by illustrating their mechanism of action related to wound healing, anti-ageing and whitening properties. The advantages and disadvantages of secretomes are compared with both plant-based and animal-derived extracts. In addition, this paper reviews the current safety standards, regulations, market products and research work related to the cosmeceutical applications of secretomes along with strategies to maintain and improve the therapeutic efficacy and production of secretomes. The future outlook of beauty industry is also presented. Lastly, we highlight significant challenges to be addressed for the clinical realization of MSC secretomes-based skin therapies as well as providing perspectives for the future direction of secretomes.

Coenzyme Q10 ameliorates the quality of mouse oocytes during in vitro culture.

Oxidative stress causes several diseases and dysfunctions in cells, including oocytes. Clearly, oxidative stress influences oocyte quality during in vitro maturation and fertilization. Here we tested the ability of coenzyme Q10 (CoQ10) to reduce reactive oxygen species (ROS) and improve mouse oocyte quality during in vitro culture. Treatment with 50 µM CoQ10 efficiently reduced ROS levels in oocytes cultured in vitro. The fertilizable form of an oocyte usually contains a cortical granule-free domain (CGFD). CoQ10 enhanced the ratio of CGFD-oocytes from 35% to 45%. However, the hardening of the zona pellucida in oocytes was not affected by CoQ10 treatment. The in vitro maturation capacity of oocytes, which was determined by the first polar body extrusion, was enhanced from 48.9% to 75.7% by the addition of CoQ10 to the culture medium. During the parthenogenesis process, the number of two-cell embryos was increased by CoQ10 from 43.5% to 67.3%. Additionally, treatment with CoQ10 increased the expression of Bcl2 and Sirt1 in cumulus cells. These results suggested that CoQ10 had a positive effect on ROS reduction, maturation rate and two-cell embryo formation in mouse oocyte culture.

Anti-ageing peptides and proteins for topical applications: a review.

Skin ageing is a cumulative result of oxidative stress, predominantly caused by reactive oxygen species (ROS). Respiration, pollutants, toxins, or ultraviolet A (UVA) irradiation produce ROS with 80% of skin damage attributed to UVA irradiation. Anti-ageing peptides and proteins are considered valuable compounds for removing ROS to prevent skin ageing and maintenance of skin health. In this review, skin ageing theory has been illustrated with a focus on the mechanism and relationship with anti-ageing peptides and proteins. The effects, classification, and transport pathways of anti-ageing peptides and proteins across skin are summarized and discussed. Over the last decade, several novel formulations and advanced strategies have been developed to overcome the challenges in the dermal delivery of proteins and peptides for skin ageing. This article also provides an in-depth review of the latest advancements in the dermal delivery of anti-ageing proteins and peptides. Based on these studies, this review prospected several semi-solid dosage forms to achieve topical applicability for anti-ageing peptides and proteins.

Comparison of chemical profiles, antioxidation, inhibition of skin extracellular matrix degradation, and anti-tyrosinase activity between mycelium and fruiting body of Cordyceps militaris and Isaria tenuipes.

CONTEXT: Cordyceps militaris and Isaria tenuipes (Cordycipitaceae) are high-value fungi that are used for health-promoting food supplements. Since laboratory cultivation has begun for these fungi, increased output has been achieved. OBJECTIVE: This study compared the chemical profiles, antioxidant, anti-tyrosinase, and skin extracellular matrix degradation inhibition between mycelium and fruiting body of C. militaris and I. tenuipes. MATERIALS AND METHODS: The antioxidative potential of 10% v/v aqueous infused extract from each fungus was separately investigated using 2,2-azinobis(3-ethylbenzo-thiazoline-6-sulphonic acid) (ABTS), 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant ability, and ferric thiocyanate methods. The inhibition against MMP-1, elastase, and hyaluronidase were determined to reveal their anti-wrinkle potential. Anti-tyrosinase activities were determined. RESULTS: C. militaris and I. tenuipes extracts were found to contain a wide range of bioactive compounds, including phenolics, flavonoids, and adenosine. A correlation was discovered between the chemical compositions and their biological activities. The extract from I. tenuipes fruiting body (IF) was highlighted as an extraordinary elastase inhibitor (IC50 = 0.006 ± 0.004 mg/mL), hyaluronidase inhibitor (IC50: 30.3 ± 3.2 mg/mL), and antioxidant via radical scavenging (ABTS IC50: 0.22 ± 0.02 mg/mL; DPPH IC50: 0.05 ± 0.02 mg/mL), thereby reducing ability (EC1: 95.3 ± 4.8 mM FeSO4/g extract) and lipid peroxidation prevention (IC50: 0.40 ± 0.11 mg/mL). IF had a three-times higher EC1 value than ascorbic acid and significantly higher elastase inhibition than epigallocatechin gallate. DISCUSSION AND CONCLUSIONS: IF is proposed as a powerful natural extract with antioxidant and anti-wrinkle properties; therefore, it is suggested for further use in pharmaceutical, cosmeceutical, and nutraceutical industries.

The molecular mechanisms of probiotic strains in improving ageing bone and muscle of d-galactose-induced ageing rats.

AIM: The aim of this study was to evaluate the molecular mechanisms of Lactobacillus strains in improving ageing of the musculoskeletal system. METHODS AND RESULTS: The anti-ageing mechanism of three probiotics strains Lactobacillus fermentum DR9, Lactobacillus paracasei OFS 0291 and L. helveticus OFS 1515 were evaluated on gastrocnemius muscle and tibia of d-galactose-induced ageing rats. Upon senescence induction, aged rats demonstrated reduced antioxidative genes CAT and SOD expression in both bone and muscle compared to the young rats (P < 0·05). Strain L. fermentum DR9 demonstrated improved expression of SOD in bone and muscle compared to the aged rats (P < 0·05). In the evaluation of myogenesis-related genes, L. paracasei OFS 0291 and L. fermentum DR9 increased the mRNA expression of IGF-1; L. helveticus OFS 1515 and L. fermentum DR9 reduced the expression of MyoD, in contrast to the aged controls (P < 0·05). Protective effects of L. fermentum DR9 on ageing muscle were believed to be contributed by increased AMPK-α2 expression. Among the osteoclastogenesis genes studied, TNF-α expression was highly elevated in tibia of aged rats, while all three probiotics strains ameliorated the expression. Lactobacillus fermentum DR9 also reduced the expression of IL-6 and TRAP in tibia when compared to the aged rats (P < 0·05). All probiotics treatment resulted in declined proinflammatory cytokines IL-1ß in muscle and bone. CONCLUSIONS: Lactobacillus fermentum DR9 appeared to be the strongest strain in modulation of musculoskeletal health during ageing. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrated the protective effects of the bacteria on muscle and bone through antioxidative and anti-inflammatory actions. Therefore, L. fermentum DR9 may serve as a promising targeted anti-ageing therapy.