CO lattice laser reverses skin aging caused by UVB.
Wang Hongyi,Guo Bingyu,Hui Qiang,Lin Feng,Tao Kai
Aging
The carbon dioxide (CO) lattice laser has been successfully used to treat facial skin photoaging induced by UV light. In this study, we analyzed the effect of CO lattice laser irradiation on skin photoaging, and investigated the underlying mechanisms. Our results demonstrate that the laser promoted collagen synthesis and proliferation of primary human skin fibroblasts, inhibited cell senescence, and induced expression of superoxide dismutase (SOD) and the signaling protein SMAD3. In addition, this laser reversed cell cycle arrest and fibroblast apoptosis induced by UVB irradiation, and restored fibroblast proliferation inhibited by SMAD3 silencing. Using a rat model of photoaging, our results show that the laser increased collagen expression and dermal thickness, demonstrating that the CO lattice laser has a profound therapeutic effect on photoaged skin. Together, our and data show that the CO lattice laser can reverse the skin aging caused by UVB, and indicate that this effect is mediated through SMAD3.
10.18632/aging.103063
Andrographolide Sodium Bisulfate Prevents UV-Induced Skin Photoaging through Inhibiting Oxidative Stress and Inflammation.
Zhan Janis Ya-Xian,Wang Xiu-Fen,Liu Yu-Hong,Zhang Zhen-Biao,Wang Lan,Chen Jian-Nan,Huang Song,Zeng Hui-Fang,Lai Xiao-Ping
Mediators of inflammation
Andrographolide sodium bisulfate (ASB), a water-soluble form made from andrographolide through sulfonating reaction, is an antioxidant and anti-inflammatory drug; however, the antiphotoaging effect of ASB has still not been revealed. Oxidative stress and inflammation are known to be responsible for ultraviolet (UV) irradiation induced skin damage and consequently premature aging. In this study, we aimed at examining the effect of ASB on UV-induced skin photoaging of mice by physiological and histological analysis of skin and examination of skin antioxidant enzymes and immunity analyses. Results showed that topical administration of ASB suppressed the UV-induced skin thickness, elasticity, wrinkles, and water content, while ASB, especially at dose of 3.6 mg/mouse, increased the skin collagen content by about 53.17%, decreased the epidermal thickness by about 41.38%, and prevented the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, ASB decreased MDA level by about 40.21% and upregulated the activities of SOD and CAT and downregulated the production of IL-1β, IL-6, IL-10, and TNF-α in UV-irradiated mice. Our study confirmed the protective effect of ASB against UV-induced photoaging and initially indicated that this effect can be attributed to its antioxidant and anti-inflammatory activities in vivo, suggesting that ASB may be a potential antiphotoaging agent.
10.1155/2016/3271451
Effects of Sphingomyelin-Containing Milk Phospholipids on Skin Hydration in UVB-Exposed Hairless Mice.
Molecules (Basel, Switzerland)
Reactive oxygen species (ROS) generated by ultraviolet (UV) exposure cause skin barrier dysfunction, which leads to dry skin. In this study, the skin moisturizing effect of sphingomyelin-containing milk phospholipids in UV-induced hairless mice was evaluated. Hairless mice were irradiated with UVB for eight weeks, and milk phospholipids (50, 100, and 150 mg/kg) were administered daily. Milk phospholipids suppressed UV-induced increase in erythema and skin thickness, decreased transepidermal water loss, and increased skin moisture. Milk phospholipids increased the expression of filaggrin, involucrin, and aquaporin3 (AQP3), which are skin moisture-related factors. Additionally, hyaluronic acid (HA) content in the skin tissue was maintained by regulating the expression of HA synthesis- and degradation-related enzymes. Milk phospholipids alleviated UV-induced decrease in the expression of the antioxidant enzymes superoxidase dismutase1 and 2, catalase, and glutathione peroxidase1. Moreover, ROS levels were reduced by regulating heme oxygenase-1 (HO-1), an ROS regulator, through milk phospholipid-mediated activation of nuclear factor erythroid-2-related factor 2 (Nrf2). Collectively, sphingomyelin-containing milk phospholipids contributed to moisturizing the skin by maintaining HA content and reducing ROS levels in UVB-irradiated hairless mice, thereby, minimizing damage to the skin barrier caused by photoaging.
10.3390/molecules27082545
Effects of Collagen-Tripeptide and Galacto-oligosaccharide Mixture on Skin Photoaging Inhibition in UVB-exposed Hairless Mice.
Photochemistry and photobiology
Collagen-tripeptide (CTP) and galacto-oligosaccharide (GOS), which improve collagen homeostasis and barrier function in the skin, are widely used in the food industry to improve wrinkle-related parameters and skin health. In this study, the photoprotective effect of CTP/GOS mixtures (3:1, 1:1, and 1:3) in ultraviolet (UV) B-irradiated hairless mice was examined. Skin parameter analysis, histological approaches, molecular biology techniques and HPLC analysis were applied to investigate the photoaging protective effect, signaling pathways and changes in the microbiota. Oral administration of CTP/GOS mixtures ameliorated photoaged physical parameters and serum levels of pro-inflammatory cytokines compared to UV-irradiated control group. Administration of the 1:3 mixture showed significant changes in the extracellular matrix-related gene expression compared to other mixture groups. The cecal short-chain fatty acid (SCFA) content showed a significant increase in the CTP/GOS mixed group with a higher GOS content than the control group. In the 16S rRNA-based analysis of cecal microbiota, the relative abundance ratio of the Akkermansia genus belonging to the Verrucomicrobia phylum was higher in CTP and GOS mixture-administered groups than in the UV-irradiated control group. Taken together, CTP/GOS mixtures showed a synergistic effect on photoprotective activity through changes in the gene expression, cytokine levels and intestinal microbiota composition.
10.1111/php.13618
Rosmarinic acid alleviates ultraviolet-mediated skin aging via attenuation of mitochondrial and ER stress responses.
Experimental dermatology
Chronic exposure to Ultraviolet B radiation (UV-B) evokes a myriad of toxic signalling events in the irradiated skin. One of such response is ER stress, which is known to exacerbate photodamage responses. Also, recent literature has highlighted the adverse impact of environmental toxicants on mitochondrial dynamics and mitophagy. Impaired mitochondrial dynamics escalates oxidative damage and causes apoptosis. There have been evidences that support crosstalk between ER stress and mitochondrial dysfunction. However, mechanistic clarification is still needed to verify the interactions between UPR responses and mitochondrial dynamics impairment in UV-B-induced photodamage models. Lastly, plant-based natural agents have garnered attention as therapeutic agents against skin photodamage. Thus, gaining mechanistic insights of plant-based natural agents is required for their application and feasibility in clinical settings. With this aim in view, this study was performed in primary human dermal fibroblasts (HDFs) and Balb/C mice. Different parameters regarding mitochondrial dynamics, ER stress, intracellular damage and histological damage were analyzed using western blot, rt-PCR and microscopy. We demonstrated that UV-B exposure leads to induction of UPR responses, upregulation of Drp-1 and inhibition of mitophagy. Further, 4-PBA treatment leads to reversal of these noxious stimuli in irradiated HDF cells, thereby, indicating an upstream role of UPR induction in mitophagy inhibition. Also, we explored the therapeutic effect of Rosmarinic acid (RA) against ER stress and impaired mitophagy in photodamage models. RA prevents intracellular damage via alleviation of ER stress and mitophagic responses in HDFs and irradiated Balb/C mice skin. The current study summarizes the mechanistic insights into UVB-mediated intracellular damage and role of natural plant-based agent (RA) in ameliorating these toxic responses.
10.1111/exd.14773
Exploring the potential of the nano-based sunscreens and antioxidants for preventing and treating skin photoaging.
Chemosphere
Excessive exposure to sunlight, especially UV irradiation, causes skin photodamage. Sunscreens, such as TiO and ZnO, can potentially prevent UV via scattering, reflection, and absorption. Topical antioxidants are another means of skin photoprotection. Developing nanoparticles for sunscreens and antioxidants is recommended for photoaging prevention and treatment as it can improve uncomfortable skin appearance, stability, penetration, and safety. This study reviewed the effects of nano-sized sunscreens and antioxidants on skin photoprevention by examining published studies and articles from PubMed, Scopus, and Google Scholar, which explore the topics of skin photoaging, skin senescence, UV radiation, keratinocyte, dermal fibroblast, sunscreen, antioxidant, and nanoparticle. The researchers of this study also summarized the nano-based UV filters and therapeutics for mitigating skin photoaging. The skin photodamage mechanisms are presented, followed by the introduction of current skin photoaging treatment. The different nanoparticle types used for topical delivery were also explored in this study. This is followed by the mechanisms of how nanoparticles improve the UV filters and antioxidant performance. Lastly, recent investigations were reviewed on nanoparticulate sunscreens and antioxidants in skin photoaging management. Sunscreens and antioxidants for topical application have different concepts. Topical antioxidants are ideal for permeating into the skin to exhibit free radical scavenging activity, while UV filters are prescribed to remain on the skin surface without absorption to exert the UV-blocking effect without causing toxicity. The nanoparticle design strategy for meeting the different needs of sunscreens and antioxidants is also explored in this study. Although the benefits of using nanoparticles for alleviating photodamage are well-established, more animal-based and clinical studies are necessary.
10.1016/j.chemosphere.2023.140702
Study of Carnosine's effect on nude mice skin to prevent UV-A damage.
Radrezza Silvia,Carini Marina,Baron Giovanna,Aldini Giancarlo,Negre-Salvayre Anne,D'Amato Alfonsina
Free radical biology & medicine
The skin is an important barrier against external attacks from bacteria, radicals, or radiations. UV-A radiations cause significant impairment of this barrier, inducing inflammation, oxidative stress, and wrinkle formation, thereby promoting photoaging. Previous studies reported that carnosine, a potent antioxidant, and carbonyl scavenger agent, may prevent photoaging features in the skin of hairless mice exposed to UV-A radiations. In the present study, we used a quantitative proteomic approach to analyze the changes evoked by carnosine in the skin proteome of hairless mice exposed to UV-A. This approach allowed to quantify more than 2480 proteins, among them consistent differences were observed for 89 proteins in UV-A exposed vs control unexposed skins, and 252 proteins in UV-A-exposed skin preventively treated by carnosine (UVAC) vs UV-A. Several functional pathways were altered in the skins of UV-A exposed hairless mice, including the integrin-linked kinase, calcium signaling, fibrogenesis, cell migration and filament formation. An impairment of mitochondrial function and metabolism was observed, with an up-regulation of cytochrome C oxidase 6B1 and NADH: ubiquinone oxidoreductase S8. Skins pre-treated by carnosine were prevented from UV-A induced proteome alterations. In conclusion, our study emphasizes the potency of a proteomic approach to identify the consequences of UV radiations in the skins, and points out the capacity of carnosine to prevent the alterations of skin proteome evoked by UV-A.
10.1016/j.freeradbiomed.2021.07.010
Skin penetration and UV-damage prevention by nanoberries.
Bucci Paula,Prieto María Jimena,Milla Laura,Calienni María Natalia,Martinez Luis,Rivarola Viviana,Alonso Silvia,Montanari Jorge
Journal of cosmetic dermatology
BACKGROUND:Ethanolic extract from blueberry (Vaccinium myrtillus) is rich in anthocyanins and thus exhibits antioxidant activity. On the other hand, ultradeformable liposomes are capable of penetrating to the impermeable barrier of skin. Nanoberries are ultradeformable liposomes carrying blueberry extract. OBJECTIVES:In this study, their capacity to penetrate the stratum corneum and photodamage prevention were tested, with the aim of developing a topical formulation for skin protection from environmental damage. METHODS:Nanoberries were prepared by lipid film resuspension with ethanolic extract from blueberry, followed by sonication and incorporation to a gel. Size, zeta potential, deformability, rheology, and viscoelasticity were determined. Toxicity was assessed in vivo in zebrafish model, while in vitro cytotoxicity assay was performed on HaCaT and HEK-293T cell lines. Skin penetration was evaluated with the Saarbrücken penetration model followed by tape stripping, cryosection, or optical sectioning. UV-damage protection and photoprotection were determined by ad hoc methods with UVA, UVB, and UVC radiation on HaCaT cells. Wound assay was performed on HaCaT cells. RESULTS:Nanoberries of about 100 nm, with differential elastic properties, did penetrate the stratum corneum, with low toxicity. When HaCaT cells were exposed to UV radiation in the presence of nanoberries, their viability was maintained. CONCLUSIONS:Nanoberries could be effective to protect the skin from sun photodamage.
10.1111/jocd.12436
Alterations of the pigmentation system in the aging process.
Kang Hee Young,Lee Jin Wook,Papaccio Federica,Bellei Barbara,Picardo Mauro
Pigment cell & melanoma research
Human skin aging is a natural phenomenon that results from continuous exposure to intrinsic (time, genetic factors, hormones) as well as extrinsic factors (UV exposure, pollution, tobacco). In areas that are frequently exposed to the sun, photoaging blends with the process of intrinsic aging, resulting in an increased senescent cells number and consequently accelerating the aging process. The severity of photodamage depends on constitutional factors, including skin phototype (skin color, tanning capacity), intensity, and duration of sunlight/UV exposure. Aging affects nearly every aspect of cutaneous biology, including pigmentation. Clinically, the phenotype of age pigmented skin has a mottled, uneven color, primarily due to age spots, with or without hypopigmentation. Uneven pigmentation might be attributed to the hyperactivation of melanocytes, altered distribution of pigment, and turnover. In addition to direct damage to pigment-producing cells, photodamage alters the physiological crosstalk between keratinocytes, fibroblasts, endothelial cells, and melanocytes responsible for natural pigmentation homeostasis. Interestingly, age-independent diffuse expression of senescence-associated markers in the dermal and epidermal compartment is also associated with vitiligo, suggesting that premature senescence plays an important role in the pathology.
10.1111/pcmr.12994
Ferulic Acid: Signaling Pathways in Aging.
Drug research
The need for clinical remedies to the multiple age-related deficiencies in skin function brought on by extrinsic and intrinsic causes is increased by these demographic changes. Reactive oxygen species (ROS), mitochondrial deoxyribonucleic acid (mtDNA) mutations, telomere shortening, as well as other factors, contribute to the aging of the skin. In this overview, the issue of human skin aging is introduced, along with several pathways and the protective effects of ferulic acid in light of current patents. The complex antioxidant effect of ferulic acid depends on the "sweeping" away of free radicals as well as the suppression of the synthesis of ROS or nitrogen. Furthermore, Cu (II) or Fe protonated metal ions are chelated by this acid (II). Ferulic acid is a free radical scavenger as well as an enzyme inhibitor, increasing the activity of enzymes that scavenge free radicals while decreasing the activity of enzymes that speed up the creation of free radicals. AMPK signalling, which can regulate cellular homeostasis, stress tolerance, cell survival and proliferation, cell death, and autophagy, has recently been linked to aging and lifespan. Therefore, Caenorhabditis elegans (C. elegans) and rodents had longer life-spans due to specific AMPK activation. By inhibiting the TGF-β/Smad signalling pathway, UV irradiation can reduce the production of procollagen. Glycation changes the skin's physical characteristics, making it less elastic and stiffer. . Excessive free radicals simultaneously trigger the nuclear factor kappa B (NF- κB) signalling pathway, increasing TNF levels and matrix metalloproteinase production (MMPs).
10.1055/a-2061-7129
Galectin-7 reprograms skin carcinogenesis by fostering innate immune evasive programs.
Cell death and differentiation
Non-melanoma skin cancer (NMSC) has risen dramatically as a result of chronic exposure to sunlight ultraviolet (UV) radiation, climatic changes and clinical conditions associated with immunosuppression. In spite of considerable progress, our understanding of the mechanisms that control NMSC development and their associated molecular and immunological landscapes is still limited. Here we demonstrated a critical role for galectin-7 (Gal-7), a β-galactoside-binding protein preferentially expressed in skin tissue, during NMSC development. Transgenic mice (Tg46) overexpressing Gal-7 in keratinocytes showed higher number of papillomas compared to WT mice or mice lacking Gal-7 (Lgals7) when subjected to a skin carcinogenesis protocol, in which tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA) and tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were sequentially administered. RNAseq analysis of Tg46 tumor lesions revealed a unique profile compatible with cells of the myelomonocytic lineage infiltrating these tumors, an effect that was substantiated by a higher number of CD11bGr1 cells in tumor-draining lymph nodes. Heightened c-Met activation and Cxcl-1 expression in Tg46 lesions suggested a contribution of this pathway to the recruitment of these cells. Remarkably, Gal-7 bound to the surface of CD11bLy6CLy6G monocytic myeloid cells and enhanced their immunosuppressive activity, as evidenced by increased IL-10 and TGF-β secretion, and higher T-cell inhibitory activity. In vivo, carcinogen-treated Lgals7 animals adoptively transferred with Gal-7-conditioned monocytic myeloid cells developed higher number of papillomas, whereas depletion of these cells in Tg46-treated mice led to reduction in the number of tumors. Finally, human NMSC biopsies showed increased LGALS7 mRNA and Gal-7 protein expression and displayed transcriptional profiles associated with myeloid programs, accompanied by elevated CXCL1 expression and c-Met activation. Thus, Gal-7 emerges as a critical mediator of skin carcinogenesis and a potential therapeutic target in human NMSC.
10.1038/s41418-022-01108-7
TGFβ Signaling in Photoaging and UV-Induced Skin Cancer.
Ke Yao,Wang Xiao-Jing
The Journal of investigative dermatology
UVR is a major etiology for premature skin aging that leads to photoaging and UV-induced skin cancers. In the skin, TGFβ signaling is a growth inhibitor for keratinocytes and a profibrotic factor in the dermis. It exerts context-dependent effects on tumor progression. Chronic UV exposure likely causes TGFβ1/SMAD3 signaling activation and contributes to metalloproteinase-induced collagen degradation and photoinflammation in photoaging. UV irradiation also causes gene mutations in key elements of the TGFβ pathway, including TGFβRI, TGFβRII, SMAD2, and SMAD4. These mutations enable tumor cells to escape from TGFβ-induced growth inhibition and induce genomic instability and cancer stem cells, leading to the initiation, progression, invasion, and metastasis of cutaneous squamous cell carcinoma (cSCC). Furthermore, UV-induced mutations cause TGFβ overexpression in the tumor microenvironment (TME) of cSCC, basal cell carcinoma (BCC), and cutaneous melanoma, resulting in inflammation, angiogenesis, cancer-associated fibroblasts, and immune inhibition, supporting cancer survival, immune evasion, and metastasis. The pleiotropic effects of TGFβ provide possible treatment options for photoaging and skin cancer. Given the high UV-induced mutational burden and immune-repressive TME seen in cSCC, BCC, and cutaneous melanoma, treatment with the combination of a TGFβ signaling inhibitor and immune checkpoint blockade could reverse immune evasion to reduce tumor growth.
10.1016/j.jid.2020.11.007
Skin delivery of epigallocatechin-3-gallate (EGCG) and hyaluronic acid loaded nano-transfersomes for antioxidant and anti-aging effects in UV radiation induced skin damage.
Avadhani Kiran S,Manikkath Jyothsna,Tiwari Mradul,Chandrasekhar Misra,Godavarthi Ashok,Vidya Shimoga M,Hariharapura Raghu C,Kalthur Guruprasad,Udupa Nayanabhirama,Mutalik Srinivas
Drug delivery
The present work attempts to develop and statistically optimize transfersomes containing EGCG and hyaluronic acid to synergize the UV radiation-protective ability of both compounds, along with imparting antioxidant and anti-aging effects. Transfersomes were prepared by thin film hydration technique, using soy phosphatidylcholine and sodium cholate, combined with high-pressure homogenization. They were characterized with respect to size, polydispersity index, zeta potential, morphology, entrapment efficiency, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), in vitro antioxidant activity and ex vivo skin permeation studies. Cell viability, lipid peroxidation, intracellular ROS levels and expression of MMPs (2 and 9) were determined in human keratinocyte cell lines (HaCaT). The composition of the transfersomes was statistically optimized by Design of Experiments using Box-Behnken design with four factors at three levels. The optimized transfersome formulation showed vesicle size, polydispersity index and zeta potential of 101.2 ± 6.0 nm, 0.245 ± 0.069 and -44.8 ± 5.24 mV, respectively. FTIR and DSC showed no interaction between EGCG and the selected excipients. XRD results revealed no form conversion of EGCG in its transfersomal form. The optimized transfersomes were found to increase the cell viability and reduce the lipid peroxidation, intracellular ROS and expression of MMPs in HaCaT cells. The optimized transfersomal formulation of EGCG and HA exhibited considerably higher skin permeation and deposition of EGCG than that observed with plain EGCG. The results underline the potential application of the developed transfersomes in sunscreen cream/lotions for improvement of UV radiation-protection along with deriving antioxidant and anti-aging effects.
10.1080/10717544.2016.1228718
Anti-Wrinkling and Anti-Melanogenic Effect of Methanol Extract.
Lorz Laura Rojas,Yoo Byong Chul,Kim Mi-Yeon,Cho Jae Youl
International journal of molecular sciences
Ultraviolet (UV) exposure causes skin photoaging leading to skin wrinkling and sagging via production of reactive oxygen species (ROS). For this reason, protection from photoaging is an important feature in cosmeceutical and dermatological products. Natural product-derived biomaterials are highly desired as future possible ingredients, because these biomaterials are often safe and effective. In this study, we aimed to characterize the skin protective activity of , traditionally used to treat sunburn and erythema. We determined the free radical scavenging, anti-melanogenic, and moisturizing effects of a methanol extract of (Pm-ME) in keratinocytes (HaCaT cells), melanocytes (B16F10 cells), and fibroblasts (human dermal fibroblasts (HDFs)) at non-cytotoxic concentrations. methanol extract contains coumaric acid as a major component, and the extract exhibited protective activity against UVB- and H₂O₂-induced cytotoxicity. This extract also suppressed the expression of (s) and in HaCaT cells. A reduction of expression under UVB- and H₂O₂-treated conditions was recovered in HaCaT cells by Pm-ME. This extract displayed significant free radical scavenging activity according to the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) assay. The Pm-ME also upregulated the expression levels of () and () in HaCaT cells, indicating a putative moisturizing activity. Interestingly, the expression of collagen type 1 () gene and its promoter activity, as assessed by a reporter gene assay, were found to be increased in HDF and HEK293 cells. Similarly, Pm-ME helped recover collagen levels after UVB and H₂O₂ treatment in HDFs as well as decreased the synthesis and secretion of melanin from B16F10 melanoma cells, which may indicate a beneficial whitening cosmetic value. The p38 inhibitor SB203580 and the JNK inhibitor SP600125 suppressed and expression in H₂O₂-treated HaCaT cells. Similarly, the ERK inhibitor U0126 inhibited in Pm-ME/H₂O₂-treated HaCaT cells. These findings suggested that inhibition of JNK and p38 and activation of ERK could be targeted by Pm-ME. Therefore, Pm-ME may exert anti-photoaging and anti-melanogenic properties via the regulation of mitogen-activated protein kinase, which could be beneficial in the cosmeceutical industry.
10.3390/ijms20051043
A Review of the Role of Green Tea () in Antiphotoaging, Stress Resistance, Neuroprotection, and Autophagy.
Prasanth Mani Iyer,Sivamaruthi Bhagavathi Sundaram,Chaiyasut Chaiyavat,Tencomnao Tewin
Nutrients
Tea is one of the most widely consumed beverages worldwide, and is available in various forms. Green tea is richer in antioxidants compared to other forms of tea. Tea is composed of polyphenols, caffeine, minerals, and trace amounts of vitamins, amino acids, and carbohydrates. The composition of the tea varies depending on the fermentation process employed to produce it. The phytochemicals present in green tea are known to stimulate the central nervous system and maintain overall health in humans. Skin aging is a complex process mediated by intrinsic factors such as senescence, along with extrinsic damage induced by external factors such as chronic exposure to ultraviolet (UV) irradiation-A process known as photoaging-Which can lead to erythema, edema, sunburn, hyperplasia, premature aging, and the development of non-melanoma and melanoma skin cancers. UV can cause skin damage either directly, through absorption of energy by biomolecules, or indirectly, by increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Green tea phytochemicals are a potent source of exogenous antioxidant candidates that could nullify excess endogenous ROS and RNS inside the body, and thereby diminish the impact of photoaging. Several in vivo and in vitro studies suggest that green tea supplementation increases the collagen and elastin fiber content, and suppresses collagen degrading enzyme MMP-3 production in the skin, conferring an anti-wrinkle effect. The precise mechanism behind the anti-photoaging effect of green tea has not been explored yet. Studies using the worm model have suggested that green tea mediated lifespan extension depends on the DAF-16 pathway. Apart from this, green tea has been reported to have stress resistance and neuroprotective properties. Its ROS scavenging activity makes it a potent stress mediator, as it can also regulate the stress induced by metal ions. It is known that tea polyphenols can induce the expression of different antioxidant enzymes and hinder the DNA oxidative damage. Growing evidence suggests that green tea can also be used as a potential agent to mediate neurodegenerative diseases, including Alzheimer's disease. EGCG, an abundant catechin in tea, was found to suppress the neurotoxicity induced by Aβ as it activates glycogen synthase kinase-3β (GSK-3β), along with inhibiting c-Abl/FE65-the cytoplasmic nonreceptor tyrosine kinase which is involved in the development of the nervous system and in nuclear translocation. Additionally, green tea polyphenols induce autophagy, thereby revitalizing the overall health of the organism consuming it. Green tea was able to activate autophagy in HL-60 xenographs by increasing the activity of PI3 kinase and BECLIN-1. This manuscript describes the reported anti-photoaging, stress resistance, and neuroprotective and autophagy properties of one of the most widely known functional foods-green tea.
10.3390/nu11020474
Melasolv™: a potential preventive and depigmenting agent for the senescence of melanocytes.
Frontiers in molecular biosciences
Senescent melanocytes are major contributors to age-related changes in the skin, highlighting the contribution to skin aging. Moreover, prolonged photodamage, such as that caused by UV exposure, can result in melanin accumulation and accelerated melanocyte senescence, thereby exacerbating aging. Melasolv™ is a substance that induces potent depigmentation effects and exhibits low toxicity. The present study aimed to investigate the potential effect of Melasolv™ on senescent melanocytes. We profiled the transcriptomics of Melasolv™-treated melanocytes and identified the possible mechanism of action (MOA) and targets using connectivity mapping analysis. We identified differentially expressed genes in response to treatment with Melasolv™ and validated the data using quantitative real-time PCR. Moreover, we performed an β-gal assay in senescent melanocytes for further validation. Melasolv™ reduced β-gal and melanin levels in senescent melanocytes. Moreover, the identified MOAs are associated with anti-aging and anti-senescence effects. Our findings clearly indicate that Melasolv™ not only exhibits anti-senescent properties but can also potentially alleviate melanin accumulation in senescent cells. These findings could have far-reaching implications in the treatment of age-related photodamaged skin conditions, such as senile lentigo and melasma.
10.3389/fmolb.2023.1228640
Molecular mechanisms of green tea polyphenols with protective effects against skin photoaging.
Roh Eunmiri,Kim Jong-Eun,Kwon Jung Yeon,Park Jun Seong,Bode Ann M,Dong Zigang,Lee Ki Won
Critical reviews in food science and nutrition
Whereas green tea has historically been consumed in high quantities in Northeast Asia, its popularity is also increasing in many Western countries. Green tea is an abundant source of plant polyphenols exhibiting numerous effects that are potentially beneficial for human health. Accumulating evidence suggests that green tea polyphenols confer protective effects on the skin against ultraviolet (UV) irradiation-induced acceleration of skin aging, involving antimelanogenic, antiwrinkle, antioxidant, and anti-inflammatory effects as well as prevention of immunosuppression. Melanin pigmentation in the skin is a major defense mechanism against UV irradiation, but pigmentation abnormalities such as melasma, freckles, senile lentigines, and other forms of melanin hyperpigmentation can also cause serious health and aesthetic issues. Furthermore, UV irradiation initiates the degradation of fibrillar collagen and elastic fibers, promoting the process of skin aging through deep wrinkle formation and loss of tissue elasticity. UV irradiation-induced formation of free radicals also contributes to accelerated photoaging. Additionally, immunosuppression caused by UV irradiation plays an important role in photoaging and skin carcinogenesis. In this review, we summarize the current literature regarding the antimelanogenic, antiwrinkle, antioxidant, and immunosuppression preventive mechanisms of green tea polyphenols that have been demonstrated to protect against UV irradiation-stimulated skin photoaging, and gauge the quality of evidence supporting the need for clinical studies using green tea polyphenols as anti-photoaging agents in novel cosmeceuticals.
10.1080/10408398.2014.1003365
Randomized controlled trial of fractionated laser resurfacing on aged skin as prophylaxis against actinic neoplasia.
The Journal of clinical investigation
BACKGROUNDThe loss of insulin-like growth factor 1 (IGF-1) expression in senescent dermal fibroblasts during aging is associated with an increased risk of nonmelanoma skin cancer (NMSC). We tested how IGF-1 signaling can influence photocarcinogenesis during chronic UVB exposure to determine if fractionated laser resurfacing (FLR) of aged skin, which upregulates dermal IGF-1 levels, can prevent the occurrence of actinic keratosis (AK) and NMSC.METHODSA human skin/immunodeficient mouse xenografting model was used to test the effects of a small molecule inhibitor of the IGF-1 receptor on chronic UVB radiation. Subsequently, the durability of FLR treatment was tested on a cohort of human participants aged 65 years and older. Finally, 48 individuals aged 60 years and older with considerable actinic damage were enrolled in a prospective randomized clinical trial in which they underwent a single unilateral FLR treatment of one lower arm. Numbers of AKs/NMSCs were recorded on both extremities for up to 36 months in blinded fashion.RESULTSXenografting studies revealed that chronic UVB treatment with a topical IGF-1R inhibitor resulted in a procarcinogenic response. A single FLR treatment was durable in restoring appropriate UVB response in geriatric skin for at least 2 years. FLR resulted in sustained reduction in numbers of AKs and decreased numbers of NMSCs in the treated arm (2 NMSCs) versus the untreated arm (24 NMSCs).CONCLUSIONThe elimination of senescent fibroblasts via FLR reduced the procarcinogenic UVB response of aged skin. Thus, wounding therapies are a potentially effective prophylaxis for managing high-risk populations.TRIAL REGISTRATIONClinicalTrials.gov (NCT03906253).FUNDINGNational Institutes of Health, Veterans Administration.
10.1172/JCI150972
A hairy tale: SIRT7 safeguards skin stem cells during aging.
Simon Matthew,Emmrich Stephan,Seluanov Andrei,Gorbunova Vera
The EMBO journal
Stem cell regulation during both normal development and aging has become one of the fastest growing topics in biology. Here, new work by Li et al (2020) offers insight into the aging process within epithelial skin stem cells and highlights how SIRT7, a member of the sirtuin family of protein deacylases and mono-ADP ribosylases, protects adult hair follicle stem cells from aging by ensuring their hair cycle progression.
10.15252/embj.2020106294
Modulation of fracture healing by the transient accumulation of senescent cells.
eLife
Senescent cells have detrimental effects across tissues with aging but may have beneficial effects on tissue repair, specifically on skin wound healing. However, the potential role of senescent cells in fracture healing has not been defined. Here, we performed an in silico analysis of public mRNAseq data and found that senescence and senescence-associated secretory phenotype (SASP) markers increased during fracture healing. We next directly established that the expression of senescence biomarkers increased markedly during murine fracture healing. We also identified cells in the fracture callus that displayed hallmarks of senescence, including distension of satellite heterochromatin and telomeric DNA damage; the specific identity of these cells, however, requires further characterization. Then, using a genetic mouse model () containing a -driven luciferase reporter, we demonstrated transient in vivo senescent cell accumulation during callus formation. Finally, we intermittently treated young adult mice following fracture with drugs that selectively eliminate senescent cells ('senolytics', Dasatinib plus Quercetin), and showed that this regimen both decreased senescence and SASP markers in the fracture callus and significantly accelerated the time course of fracture healing. Our findings thus demonstrate that senescent cells accumulate transiently in the murine fracture callus and, in contrast to the skin, their clearance does not impair but rather improves fracture healing.
10.7554/eLife.69958
Persistent JunB activation in fibroblasts disrupts stem cell niche interactions enforcing skin aging.
Cell reports
Fibroblasts residing in the connective tissues constitute the stem cell niche, particularly in organs such as skin. Although the effect of fibroblasts on stem cell niches and organ aging is an emerging concept, the underlying mechanisms are largely unresolved. We report a mechanism of redox-dependent activation of transcription factor JunB, which, through concomitant upregulation of p16 and repression of insulin growth factor-1 (IGF-1), initiates the installment of fibroblast senescence. Fibroblast senescence profoundly disrupts the metabolic and structural niche, and its essential interactions with different stem cells thus enforces depletion of stem cells pools and skin tissue decline. In fact, silencing of JunB in a fibroblast-niche-specific manner-by reinstatement of IGF-1 and p16 levels-restores skin stem cell pools and overall skin tissue integrity. Here, we report a role of JunB in the control of connective tissue niche and identified targets to combat skin aging and associated pathologies.
10.1016/j.celrep.2021.109634
Sensitive and Selective Dual-Mode Responses to Reactive Oxygen Species by Chiral Manganese Dioxide Nanoparticles for Antiaging Skin.
Advanced materials (Deerfield Beach, Fla.)
Excessive accumulation of reactive oxygen species (ROS) can lead to oxidative stress and oxidative damage, which is one of the important factors for aging and age-related diseases. Therefore, real-time monitoring and the moderate elimination of ROS is extremely important. In this study, a ROS-responsive circular dichroic (CD) at 553 nm and magnetic resonance imaging (MRI) dual-signals chiral manganese oxide (MnO ) nanoparticles (NPs) are designed and synthesized. Both the CD and MRI signals show excellent linear ranges for intracellular hydrogen peroxide (H O ) concentrations, with limits of detection (LOD) of 0.0027 nmol/10 cells and 0.016 nmol/10 cells, respectively. The lower LOD achieved with CD detection may be attributable to its higher anti-interference capability from the intracellular matrix. Importantly, ROS-induced cell aging is intervened by chiral MnO NPs via redox reactions with excessive intracellular ROS. In vivo experiments confirm that chiral MnO NPs effectively eliminate ROS in skin tissue, reduce oxidative stress levels, and alleviate skin aging. This approach provides a new strategy for the diagnosis and treatment of age-related diseases.
10.1002/adma.202308469
Human organ rejuvenation by VEGF-A: Lessons from the skin.
Science advances
Transplanting aged human skin onto young SCID/beige mice morphologically rejuvenates the xenotransplants. This is accompanied by angiogenesis, epidermal repigmentation, and substantial improvements in key aging-associated biomarkers, including ß-galactosidase, p16, SIRT1, PGC1α, collagen 17A, and MMP1. Angiogenesis- and hypoxia-related pathways, namely, vascular endothelial growth factor A (VEGF-A) and HIF1A, are most up-regulated in rejuvenated human skin. This rejuvenation cascade, which can be prevented by VEGF-A-neutralizing antibodies, appears to be initiated by murine VEGF-A, which then up-regulates VEGF-A expression/secretion within aged human skin. While intradermally injected VEGF-loaded nanoparticles suffice to induce a molecular rejuvenation signature in aged human skin on old mice, VEGF-A treatment improves key aging parameters also in isolated, organ-cultured aged human skin, i.e., in the absence of functional skin vasculature, neural, or murine host inputs. This identifies VEGF-A as the first pharmacologically pliable master pathway for human organ rejuvenation in vivo and demonstrates the potential of our humanized mouse model for clinically relevant aging research.
10.1126/sciadv.abm6756
Miniaturized, light-adaptive, wireless dosimeters autonomously monitor exposure to electromagnetic radiation.
Kwon Kyeongha,Heo Seung Yun,Yoo Injae,Banks Anthony,Chan Michelle,Lee Jong Yoon,Park Jun Bin,Kim Jeonghyun,Rogers John A
Science advances
Exposure to electromagnetic radiation (EMR) from the sun and from artificial lighting systems represents a modifiable risk factor for a broad range of health conditions including skin cancer, skin aging, sleep and mood disorders, and retinal damage. Technologies for personalized EMR dosimetry could guide lifestyles toward behaviors that ensure healthy levels of exposure. Here, we report a millimeter-scale, ultralow-power digital dosimeter platform that provides continuous EMR dosimetry in an autonomous mode at one or multiple wavelengths simultaneously, with time-managed wireless, long-range communication to standard consumer devices. A single, small button cell battery supports a multiyear life span, enabled by the combined use of a light-powered, accumulation mode of detection and a light-adaptive, ultralow-power circuit design. Field studies demonstrate single- and multimodal dosimetry platforms of this type, with a focus on monitoring short-wavelength blue light from indoor lighting and display systems and ultraviolet/visible/infrared radiation from the sun.
10.1126/sciadv.aay2462
Neurobiology, Stem Cell Biology, and Immunology: An Emerging Triad for Understanding Tissue Homeostasis and Repair.
Annual review of cell and developmental biology
The peripheral nervous system (PNS) endows animals with the remarkable ability to sense and respond to a dynamic world. Emerging evidence shows the PNS also participates in tissue homeostasis and repair by integrating local changes with organismal and environmental changes. Here, we provide an in-depth summary of findings delineating the diverse roles of peripheral nerves in modulating stem cell behaviors and immune responses under steady-state conditions and in response to injury and duress, with a specific focus on the skin and the hematopoietic system. These examples showcase how elucidating neuro-stem cell and neuro-immune cell interactions provides a conceptual framework that connects tissue biology and local immunity with systemic bodily changes to meet varying demands. They also demonstrate how changes in these interactions can manifest in stress, aging, cancer, and inflammation, as well as how these findings can be harnessed to guide the development of new therapeutics.
10.1146/annurev-cellbio-120320-032429
The dark side of daylight: photoaging and the tumor microenvironment in melanoma progression.
The Journal of clinical investigation
Continued thinning of the atmospheric ozone, which protects the earth from damaging ultraviolet radiation (UVR), will result in elevated levels of UVR reaching the earth's surface, leading to a drastic increase in the incidence of skin cancer. In addition to promoting carcinogenesis in skin cells, UVR is a potent extrinsic driver of age-related changes in the skin known as "photoaging." We are in the preliminary stages of understanding of the role of intrinsic aging in melanoma, and the tumor-permissive effects of photoaging on the skin microenvironment remain largely unexplored. In this Review, we provide an overview of the impact of UVR on the skin microenvironment, addressing changes that converge or diverge with those observed in intrinsic aging. Intrinsic and extrinsic aging promote phenotypic changes to skin cell populations that alter fundamental processes such as melanogenesis, extracellular matrix deposition, inflammation, and immune response. Given the relevance of these processes in cancer, we discuss how photoaging might render the skin microenvironment permissive to melanoma progression.
10.1172/JCI143763
The cIAP ubiquitin ligases sustain type 3 γδ T cells and ILC during aging to promote barrier immunity.
The Journal of experimental medicine
Early-life cues shape the immune system during adulthood. However, early-life signaling pathways and their temporal functions are not well understood. Herein, we demonstrate that the cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1/2), which are E3 ubiquitin ligases, sustain interleukin (IL)-17-producing γ δ T cells (γδT17) and group 3 innate lymphoid cells (ILC3) during late neonatal and prepubescent life. We show that cell-intrinsic deficiency of cIAP1/2 at 3-4 wk of life leads to downregulation of the transcription factors cMAF and RORγt and failure to enter the cell cycle, followed by progressive loss of γδT17 cells and ILC3 during aging. Mice deficient in cIAP1/2 have severely reduced γδT17 cells and ILC3, present with suboptimal γδT17 responses in the skin, lack intestinal isolated lymphoid follicles, and cannot control intestinal bacterial infection. Mechanistically, these effects appear to be dependent on overt activation of the non-canonical NF-κB pathway. Our data identify cIAP1/2 as early-life molecular switches that establish effective type 3 immunity during aging.
10.1084/jem.20221534
Associations of four biological age markers with child development: A multi-omic analysis in the European HELIX cohort.
eLife
Background:While biological age in adults is often understood as representing general health and resilience, the conceptual interpretation of accelerated biological age in children and its relationship to development remains unclear. We aimed to clarify the relationship of accelerated biological age, assessed through two established biological age indicators, telomere length and DNA methylation age, and two novel candidate biological age indicators, to child developmental outcomes, including growth and adiposity, cognition, behavior, lung function and the onset of puberty, among European school-age children participating in the HELIX exposome cohort. Methods:The study population included up to 1173 children, aged between 5 and 12 years, from study centres in the UK, France, Spain, Norway, Lithuania, and Greece. Telomere length was measured through qPCR, blood DNA methylation, and gene expression was measured using microarray, and proteins and metabolites were measured by a range of targeted assays. DNA methylation age was assessed using Horvath's skin and blood clock, while novel blood transcriptome and 'immunometabolic' (based on plasma proteins and urinary and serum metabolites) clocks were derived and tested in a subset of children assessed six months after the main follow-up visit. Associations between biological age indicators with child developmental measures as well as health risk factors were estimated using linear regression, adjusted for chronological age, sex, ethnicity, and study centre. The clock derived markers were expressed as Δ age (i.e. predicted minus chronological age). Results:Transcriptome and immunometabolic clocks predicted chronological age well in the test set (=0.93 and =0.84 respectively). Generally, weak correlations were observed, after adjustment for chronological age, between the biological age indicators.Among associations with health risk factors, higher birthweight was associated with greater immunometabolic Δ age, smoke exposure with greater DNA methylation Δ age, and high family affluence with longer telomere length.Among associations with child developmental measures, all biological age markers were associated with greater BMI and fat mass, and all markers except telomere length were associated with greater height, at least at nominal significance (p<0.05). Immunometabolic Δ age was associated with better working memory (p=4 e-3) and reduced inattentiveness (p=4 e-4), while DNA methylation Δ age was associated with greater inattentiveness (p=0.03) and poorer externalizing behaviors (p=0.01). Shorter telomere length was also associated with poorer externalizing behaviors (p=0.03). Conclusions:In children, as in adults, biological aging appears to be a multi-faceted process and adiposity is an important correlate of accelerated biological aging. Patterns of associations suggested that accelerated immunometabolic age may be beneficial for some aspects of child development while accelerated DNA methylation age and telomere attrition may reflect early detrimental aspects of biological aging, apparent even in children. Funding:UK Research and Innovation (MR/S03532X/1); European Commission (grant agreement numbers: 308333; 874583).
10.7554/eLife.85104
"Deepening" Insight on Skin Aging and Anti-microbial Immunity.
Kobayashi Tetsuro,Nagao Keisuke
Cell metabolism
Skin aging is of considerable interest from various perspectives, ranging from aesthetics to cancer development. Zhang et al. (2019) elucidate an immunological consequence of aging in the adipose layer of skin. Age-dependent increases in TGF-β signaling impair fibroblast adipogenic potential that results in impaired anti-bacterial host defense.
10.1016/j.cmet.2019.02.006
Cellular Senescence in Acute and Chronic Wound Repair.
Cold Spring Harbor perspectives in biology
Cellular senescence, once thought an artifact of in vitro culture or passive outcome of aging, has emerged as fundamental to tissue development and function. The senescence mechanism importantly halts cell cycle progression to protect against tumor formation, while transiently present senescent cells produce a complex secretome (or SASP) of inflammatory mediators, proteases, and growth factors that guide developmental remodeling and tissue regeneration. Transiently present senescence is important for skin repair, where it accelerates extracellular matrix formation, limits fibrosis, promotes reepithelialization, and modulates inflammation. Unfortunately, advanced age and diabetes drive pathological accumulation of senescent cells in chronic wounds, which is perpetuated by a proinflammatory SASP, advanced glycation end-products, and oxidative damage. Although the biology of wound senescence remains incompletely understood, drugs that selectively target senescent cells are showing promise in clinical trials for diverse pathological conditions. It may not be long before senescence-targeted therapies will be available for the management, or perhaps even prevention, of chronic wounds.
10.1101/cshperspect.a041221
Somatic mutations in facial skin from countries of contrasting skin cancer risk.
Nature genetics
The incidence of keratinocyte cancer (basal cell and squamous cell carcinomas of the skin) is 17-fold lower in Singapore than the UK, despite Singapore receiving 2-3 times more ultraviolet (UV) radiation. Aging skin contains somatic mutant clones from which such cancers develop. We hypothesized that differences in keratinocyte cancer incidence may be reflected in the normal skin mutational landscape. Here we show that, compared to Singapore, aging facial skin from populations in the UK has a fourfold greater mutational burden, a predominant UV mutational signature, increased copy number aberrations and increased mutant TP53 selection. These features are shared by keratinocyte cancers from high-incidence and low-incidence populations. In Singaporean skin, most mutations result from cell-intrinsic processes; mutant NOTCH1 and NOTCH2 are more strongly selected than in the UK. Aging skin in a high-incidence country has multiple features convergent with cancer that are not found in a low-risk country. These differences may reflect germline variation in UV-protective genes.
10.1038/s41588-023-01468-x
A Tetrahedral Framework DNA-Based Bioswitchable miRNA Inhibitor Delivery System: Application to Skin Anti-Aging.
Advanced materials (Deerfield Beach, Fla.)
MicroRNA (miR)-based therapy shows strong potential; however, structural limitations pose a challenge in fully exploiting its biomedical functionality. Tetrahedral framework DNA (tFNA) has proven to be an ideal vehicle for miR therapy. Inspired by the ancient Chinese myth "Sun and Immortal Birds," a novel bioswitchable miR inhibitor delivery system (BiRDS) is designed with three miR inhibitors (the three immortal birds) and a nucleic acid core (the central sun). The BiRDS fuses miR inhibitors within the framework, maximizing their loading capacity, while allowing the system to retain the characteristics of small-sized tFNA and avoiding uncertainty associated with RNA exposure in traditional loading protocols. The RNase H-responsive sequence at the tail of each "immortal bird" enables the BiRDS to transform from a 3D to a 2D structure upon entering cells, promoting the delivery of miR inhibitors. To confirm the application potential, the BiRDS is used to deliver the miR-31 inhibitor, with antiaging effects on hair follicle stem cells, into a skin aging model. Superior skin penetration ability and RNA delivery are observed with significant anti-aging effects. These findings demonstrate the capability and editability of the BiRDS to improve the stability and delivery efficacy of miRs for future innovations.
10.1002/adma.202204287
BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates.
Nucleic acids research
Aging in humans is intricately linked with alterations in circadian rhythms concomitant with physiological decline and stem cell exhaustion. However, whether the circadian machinery directly regulates stem cell aging, especially in primates, remains poorly understood. In this study, we found that deficiency of BMAL1, the only non-redundant circadian clock component, results in an accelerated aging phenotype in both human and cynomolgus monkey mesenchymal progenitor cells (MPCs). Unexpectedly, this phenotype was mainly attributed to a transcription-independent role of BMAL1 in stabilizing heterochromatin and thus preventing activation of the LINE1-cGAS-STING pathway. In senescent primate MPCs, we observed decreased capacity of BMAL1 to bind to LINE1 and synergistic activation of LINE1 expression. Likewise, in the skin and muscle tissues from the BMAL1-deficient cynomolgus monkey, we observed destabilized heterochromatin and aberrant LINE1 transcription. Altogether, these findings uncovered a noncanonical role of BMAL1 in stabilizing heterochromatin to inactivate LINE1 that drives aging in primate cells.
10.1093/nar/gkac146
Remodeling of the Collagen Matrix in Aging Skin Promotes Melanoma Metastasis and Affects Immune Cell Motility.
Cancer discovery
Physical changes in skin are among the most visible signs of aging. We found that young dermal fibroblasts secrete high levels of extracellular matrix (ECM) constituents, including proteoglycans, glycoproteins, and cartilage-linking proteins. The most abundantly secreted was HAPLN1, a hyaluronic and proteoglycan link protein. HAPLN1 was lost in aged fibroblasts, resulting in a more aligned ECM that promoted metastasis of melanoma cells. Reconstituting HAPLN1 inhibited metastasis in an aged microenvironment, in 3-D skin reconstruction models, and . Intriguingly, aged fibroblast-derived matrices had the opposite effect on the migration of T cells, inhibiting their motility. HAPLN1 treatment of aged fibroblasts restored motility of mononuclear immune cells, while impeding that of polymorphonuclear immune cells, which in turn affected regulatory T-cell recruitment. These data suggest that although age-related physical changes in the ECM can promote tumor cell motility, they may adversely affect the motility of some immune cells, resulting in an overall change in the immune microenvironment. Understanding the physical changes in aging skin may provide avenues for more effective therapy for older patients with melanoma. SIGNIFICANCE: These data shed light on the mechanochemical interactions that occur between aged skin, tumor, and immune cell populations, which may affect tumor metastasis and immune cell infiltration, with implications for the efficacy of current therapies for melanoma...
10.1158/2159-8290.CD-18-0193
Senescent human melanocytes drive skin ageing via paracrine telomere dysfunction.
The EMBO journal
Cellular senescence has been shown to contribute to skin ageing. However, the role of melanocytes in the process is understudied. Our data show that melanocytes are the only epidermal cell type to express the senescence marker p16 during human skin ageing. Aged melanocytes also display additional markers of senescence such as reduced HMGB1 and dysfunctional telomeres, without detectable telomere shortening. Additionally, senescent melanocyte SASP induces telomere dysfunction in paracrine manner and limits proliferation of surrounding cells via activation of CXCR3-dependent mitochondrial ROS. Finally, senescent melanocytes impair basal keratinocyte proliferation and contribute to epidermal atrophy in vitro using 3D human epidermal equivalents. Crucially, clearance of senescent melanocytes using the senolytic drug ABT737 or treatment with mitochondria-targeted antioxidant MitoQ suppressed this effect. In conclusion, our study provides proof-of-concept evidence that senescent melanocytes affect keratinocyte function and act as drivers of human skin ageing.
10.15252/embj.2019101982
The extracellular matrix dictates regional competence for tumour initiation.
Nature
The skin epidermis is constantly renewed throughout life. Disruption of the balance between renewal and differentiation can lead to uncontrolled growth and tumour initiation. However, the ways in which oncogenic mutations affect the balance between renewal and differentiation and lead to clonal expansion, cell competition, tissue colonization and tumour development are unknown. Here, through multidisciplinary approaches that combine in vivo clonal analysis using intravital microscopy, single-cell analysis and functional analysis, we show how SmoM2-a constitutively active oncogenic mutant version of Smoothened (SMO) that induces the development of basal cell carcinoma-affects clonal competition and tumour initiation in real time. We found that expressing SmoM2 in the ear epidermis of mice induced clonal expansion together with tumour initiation and invasion. By contrast, expressing SmoM2 in the back-skin epidermis led to a clonal expansion that induced lateral cell competition without dermal invasion and tumour formation. Single-cell analysis showed that oncogene expression was associated with a cellular reprogramming of adult interfollicular cells into an embryonic hair follicle progenitor (EHFP) state in the ear but not in the back skin. Comparisons between the ear and the back skin revealed that the dermis has a very different composition in these two skin types, with increased stiffness and a denser collagen I network in the back skin. Decreasing the expression of collagen I in the back skin through treatment with collagenase, chronic UV exposure or natural ageing overcame the natural resistance of back-skin basal cells to undergoing EHFP reprogramming and tumour initiation after SmoM2 expression. Altogether, our study shows that the composition of the extracellular matrix regulates how susceptible different regions of the body are to tumour initiation and invasion.
10.1038/s41586-023-06740-y
Needle-Free Injection of Exosomes Derived from Human Dermal Fibroblast Spheroids Ameliorates Skin Photoaging.
Hu Shiqi,Li Zhenhua,Cores Jhon,Huang Ke,Su Teng,Dinh Phuong-Uyen,Cheng Ke
ACS nano
Human dermal fibroblasts (HDFs), the main cell population of the dermis, gradually lose their ability to produce collagen and renew intercellular matrix with aging. One clinical application for the autologous trans-dermis injection of HDFs that has been approved by the Food and Drug Administration aims to refine facial contours and slow down skin aging. However, the autologous HDFs used vary in quality according to the state of patients and due to many passages they undergo during expansion. In this study, factors and exosomes derived from three-dimensional spheroids (3D HDF-XOs) and the monolayer culture of HDFs (2D HDF-XOs) were collected and compared. 3D HDF-XOs expressed a significantly higher level of tissue inhibitor of metalloproteinases-1 (TIMP-1) and differentially expressed miRNA cargos compared with 2D HDF-XOs. Next, the efficacy of 3D HDF-XOs in inducing collagen synthesis and antiaging was demonstrated and in a nude mouse photoaging model. A needle-free injector was used to administer exosome treatments. 3D HDF-XOs caused increased procollagen type I expression and a significant decrease in MMP-1 expression, mainly through the downregulation of tumor necrosis factor-alpha (TNF-α) and the upregulation of transforming growth factor beta (TGF-β). In addition, the 3D-HDF-XOs group showed a higher level of dermal collagen deposition than bone marrow mesenchymal stem cell-derived exosomes. These results indicate that exosomes from 3D cultured HDF spheroids have anti-skin-aging properties and the potential to prevent and treat cutaneous aging.
10.1021/acsnano.9b04384