Mouse Skin Research Articles

Revisiting Unaddressed Safety Concerns Regarding Intense Pulsed Light Treatment: Past and Present Perspectives.

The light spectrum of intense pulsed light (IPL) comprises visible to near-infrared light. It has been widely employed in the field of aesthetics for approximately 30 years. However, several studies have demonstrated the appearance of various undesirable biomarkers on the skin after IPL irradiation, which remain elucidated. We reviewed the evolving concepts and explored the potentially harmful effects of IPL that may have been neglected in the past. Increased levels of reactive oxidative stress, p53, p16, proliferating cell nuclear antigen, interleukin-6, C-reactive protein, and cleaved caspase 3 and decreased albumin levels in human or mouse skin have been observed after IPL treatment. Visible and infrared light can exert harmful and beneficial effects on human skin. If perform improperly, IPL treatment may lead to cellular senescence, photoaging, photocarcinogenesis, thermal aging, and inflammaging. Further studies are required to verify the significance of the changes in the relevant biomarkers. The selection of treatment candidates, optimal parameters, and standardized protocols for IPL therapy are necessary.

Identification of Key Genes Related to Immune-Lipid Metabolism in Skin Barrier Damage and Analysis of Immune Infiltration.

Several physical and chemical factors regulate skin barrier function. Skin barrier dysfunction causes many inflammatory skin diseases, such as atopic dermatitis and psoriasis. Activation of the immune response may lead to damage to the epidermal barrier. Abnormal lipid metabolism is defined as abnormally high or low values of plasma lipid components such as plasma cholesterol and triglycerides. The mouse skin barrier damage model was used for RNA sequencing. Bioinformatics analysis and validation were performed. Differently expressed genes (DEGs) related to immune and lipid metabolism were screened by differentially expressed gene analysis, and the enriched biological processes and pathways of these genes were identified by GO-KEGG. The interactions between DEGs were confirmed by constructing a PPI network. GSEA, transcription factor regulatory network, and immune infiltration analyses were performed for the 10 genes. Expression validation was performed by public datasets. The expression of key genes in mouse skin tissue was detected by qPCR. The expression of differentially expressed immune cell markers in the skin was detected by immunofluorescence. Based on the trans epidermal water loss (TEWL) score, the expression of key genes was detected by qPCR before skin barrier injury, at 4h and 7d, and at recovery from injury. Il17a, Il6, Tnf, Itgam, and Cxcl1 were immune-related key genes. Pla2g2f, Ptgs2, Plb1, Pla2g3, and Pla2g2d were key genes for lipid metabolism. Database validation and experimental results revealed that the expression trends of these genes were consistent with our analyses. The research value of these genes has been demonstrated through mouse datasets and experimental validation, and future therapeutic approaches may be able to mitigate the disease by targeting these genes to modulate the function of the skin barrier.

Poly-D,L-Lactic Acid Filler Attenuates Ultraviolet B-Induced Skin Pigmentation by Reducing Destruction of the Basement Membrane

Poly-D,L-lactic acid (PDLLA) filler, which increases volume and collagen synthesis, is used for skin rejuvenation. PDLLA filler also increases M2 macrophages and IL-10. Ultraviolet (UV) radiation induces dermal hyperpigmentation by disrupting the basement membrane (BM), allowing melanin to move into the dermis. Therefore, using UV-irradiated macrophages and animal skin, we determined whether PDLLA filler decreased M1 macrophages and skin inflammation, thereby reducing BM destruction and dermal hyperpigmentation. UV radiation increased the M1 macrophage marker CD86 and TNF-α expression, which was inhibited by the treatment of macrophages with PDLLA. In fibroblasts treated with conditioned medium from UV-irradiated macrophages, NF-κB activity, NLRP3 inflammasome components (NLRP3, ASC, and pro-caspase-1), IL-18, MMP2, and MMP9 increased, but all decreased after PDLLA treatment. Similar to the in vitro study, UV-irradiated mouse skin showed increased CD86, NLRP3, ASC, pro-caspase-1, MMP2, and MMP9, which decreased after PDLLA injection. Disruption of the lamina densa of the BM and dermal pigmentation increased after UV irradiation and decreased after PDLLA injection. In conclusion, PDLLA reduced dermal pigmentation by decreasing BM destruction in UV-irradiated skin. PDLLA has the potential to reduce dermal pigmentation by regenerating the BM.

Bay 11-7082, an NF-κB Inhibitor, Prevents Post-Inflammatory Hyperpigmentation Through Inhibition of Inflammation and Melanogenesis.

Post-inflammatory hyperpigmentation (PIH) is a very common disorder of cutaneous hyperpigmentation, which poses a persistent management challenge in the fields of dermatology and esthetics. This study was designed to explore the anti-melanogenic and anti-inflammatory effects of Bay 11-7082, an NF-κB inhibitor, using small-molecule screening, to determine its potential application for PIH prevention. The molecular mechanisms were investigated invitro and exvivo in epidermis-humanized mice using melanin content, RT-PCR, and immunoblotting. Bay 11-7082 suppressed proinflammatory cytokines and ameliorated 2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis on day 15. The suppression of melanin synthesis by Bay 11-7082 was attributed to the reduction of MITF, which was induced by extracellular signal-regulated kinase activation. Bay 11-7082 reduced epidermal melanin accumulation in UVB-stimulated exvivo human epidermis as well as in the ear and tail skin of K14-stem cell factor (SCF) transgenic mice. Topical administration of Bay 11-7082 improved PIH on day 35 in the post-DNFB dorsal skin of K14-SCF transgenic mice. In conclusion, Bay 11-7082 can be considered a promising candidate for the development of a preventive topical agent for PIH.

Deep Learning With Optical Coherence Tomography for Melanoma Identification and Risk Prediction.

Malignant melanoma is the most severe skin cancer with a rising incidence rate. Several noninvasive image techniques and computer-aided diagnosis systems have been developed to help find melanoma in its early stages. However, most previous research utilized dermoscopic images to build a diagnosis model, and only a few used prospective datasets. This study develops and evaluates a convolutional neural network (CNN) for melanoma identification and risk prediction using optical coherence tomography (OCT) imaging of mice skin. Longitudinal tests are performed on four animal models: melanoma mice, dysplastic nevus mice, and their respective controls. The CNN classifies melanoma and healthy tissues with high sensitivity (0.99) and specificity (0.98) and also assigns a risk score to each image based on the probability of melanoma presence, which may facilitate early diagnosis and management of melanoma in clinical settings.

Comparative Study of Cytotoxicity and Accumulation of Boron and Lithium-Containing Drugs in Skin Melanoma Cells In Vitro.

We studied cytotoxicity and accumulation of boron and lithium by cultured human fibroblasts and human and mouse skin melanoma cell cultures. The cytotoxicity of boron and lithium drugs was assessed by MTT tests in the boron and lithium concentration range of 10-640 μg/ml. Cell viability was significantly reduced after incubation with boron and lithium at concentrations >160 μg/ml. To assess accumulation of boron and lithium, the concentration of elements was measured using inductively coupled plasma atomic emission spectrometry. Melanoma cells more intensively accumulated lithium in comparison with boron. The results indicate the possibility of safe application of lithium salts in concentrations minimally required for successful neutron capture therapy.

P2RY6 deletion promotes UVB-induced skin carcinogenesis by activating the PI3K/AKT signal pathway.

Our previous research has demonstrated that P2RY6 functions as an oncogene in DMBA/TPA-induced two-stage chemical skin carcinogenesis in mice. However, considering that human skin cancer is predominantly attributed to UV radiation from sunlight, additional investigations are needed to elucidate the role of P2RY6 in UVB-induced skin carcinogenesis. Surprisingly, we found that P2ry6-deficient mice exhibited marked promotion to UVB-induced skin papilloma formation compared with wild-type mice, suggesting its tumor-suppressive role in UVB-induced skin cancer. Additionally, a P2ry6 gene knockout promoted skin hyperplasia induced by short-term UVB irradiation, while UDP, the ligand of P2RY6, could inhibit the short-term UVB-induced increase of epiderma thickness in mouse skin. Furthermore, UVB irradiation could significantly upregulate P2RY6 expression in human and mouse skin cells. These results indicated that P2RY6 may play a crucial protective role in resisting the UVB-induced formation of skin tumors. At the molecular level, the loss of the P2RY6 gene inhibits the ubiquitination modification and expression of XPC after UVB irradiation in skin keratinocytes, resulting in the accumulation of CPDs (cyclobutane pyrimidine dimers). We have also demonstrated that P2RY6 deletion activates the PI3K/AKT signaling pathway both invitro and invivo. The CPD accumulation and acute inflammatory response enhanced by the loss of the P2RY6 gene can be reversed by an AKT inhibitor. These findings suggest that P2RY6 may act as a tumor suppressor in UVB-induced skin cancer by regulating the PI3K/AKT signaling pathway.

Extending the acute skin response spectrum to include the far-UVC.

Guidance on maximal limits for ultraviolet (UV) exposure has been developed by national and international organizations to protect against adverse effects on human skin and eyes. These guidelines consider the risk of both acute effects (i.e., erythema and photokeratitis) and delayed effects (e.g., skin and ocular cancers) when determining exposure limits, and specify the dose a person can safely receive during an 8-h period without harmful effects. The determination of these exposure limits relies on the action spectra of photobiological responses triggered by UV radiation that quantify the effectiveness of each wavelength at eliciting each of these effects. With growing interest in using far-UVC (200-235 nm) radiation to control the spread of airborne pathogens, recent arguments have emerged about revisiting exposure limits for UV wavelengths. However, the standard erythema action spectrum, which provides some of the quantitative basis for these limits, has not been extended below 240 nm. This study assists to expand the erythema action spectrum to far-UVC wavelengths using a hairless albino mice model. We estimate that inducing acute effects on mouse skin with 222 nm radiation requires a dose of 1162 mJ/cm2, well above the current ACGIH skin exposure limit of 480 mJ/cm2.

Hydroxyprolyl-Glycine in 24 H Urine Shows Higher Correlation with Meat Consumption than Prolyl-Hydroxyproline, a Major Collagen Peptide in Urine and Blood

Background. Urinary collagen peptides, the breakdown products of endogenous collagen, have been used as biomarkers for various diseases. These non-invasive biomarkers are easily measured via mass spectrometry, aiding in diagnostics and therapy effectiveness. Objectives. The objective of this study was to investigate the effects of consuming collagen-containing meat on collagen peptide composition in human blood and urine. Methods. Ten collagen peptides in 24 h urine were quantified. Results. Prolyl-hydroxyproline (Pro-Hyp) was the most abundant peptide. Except for hydroxyprolyl-glycine (Hyp-Gly), levels of other minor collagen peptides showed high correlation coefficients with Pro-Hyp (r = 0.42 vs. r > 0.8). Notably, 24 h urinary Hyp-Gly showed a correlation coefficient of r = 0.72 with meat consumption, significantly higher than the coefficient for Pro-Hyp (r = 0.37). Additionally, the levels of Pro-Hyp and Hyp-Gly in the blood of seven young women participants increased similarly after consuming fish meat, while before ingestion, only negligible amounts of Hyp-Gly were present. To examine which peptides are generated by the degradation of endogenous collagen, mouse skin was cultured. The amount of Pro-Hyp released from the skin was approximately 1000-fold higher than that of Hyp-Gly. Following consumption of collagen-containing meat, both Pro-Hyp and Hyp-Gly are released in blood and excreted into urine, although Pro-Hyp is primarily generated from endogenous collagen even under physiological conditions. Conclusion. Therefore, in 24 h urine samples, the non-negligible fraction of Pro-Hyp is contributed by endogenous collagen, making 24 h urine Hyp-Gly level a potential biomarker for evaluating meat consumption on the day.

Mitochondrial mechanotransduction through MIEF1 coordinates the nuclear response to forces.

Tissue-scale architecture and mechanical properties instruct cell behaviour under physiological and diseased conditions, but our understanding of the underlying mechanisms remains fragmentary. Here we show that extracellular matrix stiffness, spatial confinements and applied forces, including stretching of mouse skin, regulate mitochondrial dynamics. Actomyosin tension promotes the phosphorylation of mitochondrial elongation factor 1 (MIEF1), limiting the recruitment of dynamin-related protein 1 (DRP1) at mitochondria, as well as peri-mitochondrial F-actin formation and mitochondrial fission. Strikingly, mitochondrial fission is also a general mechanotransduction mechanism. Indeed, we found that DRP1- and MIEF1/2-dependent fission is required and sufficient to regulate three transcription factors of broad relevance-YAP/TAZ, SREBP1/2 and NRF2-to control cell proliferation, lipogenesis, antioxidant metabolism, chemotherapy resistance and adipocyte differentiation in response to mechanical cues. This extends to the mouse liver, where DRP1 regulates hepatocyte proliferation and identity-hallmark YAP-dependent phenotypes. We propose that mitochondria fulfil a unifying signalling function by which the mechanical tissue microenvironment coordinates complementary cell functions.

EIF6 modulates skin wound healing by upregulating keratin 6B.

Eukaryotic translation initiation factor 6 (eIF6) plays a crucial role in 60S ribosome biogenesis and protein translation, as well as in hypertrophic scar formation, but its potential role in epithelialization is still poorly understood. Herein, we found that eIF6 negatively correlated with the wound healing process. Mice with genetically knockdown eIF6 (eIF6+/-) showed faster re-epithelization as shown by the longer tongue of the newly formed epidermis. Furthermore, eIF6 ablation accelerated the wound healing process by targeting basal keratinocytes in the eIF6 keratinocyte-conditional knockout (eIF6f/+; Krt5-Cre+) mice. Mechanistically, keratin 6B, an important wound-activated protein, was significantly upregulated in eIF6f/+; Krt5-Cre+ mice skin as proved by RNA-seq, western immunoblots, and immunofluorescence staining. Moreover, an elevated level of KRT6B and accelerated proliferative capacity were also observed in stable knockdown eIF6 HaCaT cells. Taken together, eIF6 downregulation could accelerate epithelialization by upregulating KRT6B expression and promoting keratinocyte proliferation. Our results for the first time indicate that eIF6 might be a novel target to regulate re-epithelialization.

Phosphatidylserine Topically Attenuates Imiquimod-induced Psoriasis Through Inflammation Inhibition in Mice.

Psoriasis is a chronic skin condition that is associated with persistent inflammation and skin lesions. Topical therapy has been a promising approach to the alleviation of psoriasis through the application of anti-inflammatory agents. Phosphatidylserine (PS) administration has shown anti-inflammatory effects in the trials. Consequently, the objective of this study was to evaluate the effects of topical PS on the potential improvement of an imiquimod (IMQ)-induced psoriasis model. Additionally, cyclosporine A was utilized as a comparative anti-psoriatic agent in our study. The psoriasis model was established by topically applying IMQ to the dorsal skin of mice once daily for five consecutive days. The efficacy of topical PS was assessed using the Psoriasis Area and Severity Index (PASI) score to evaluate skin lesions. Subsequently, the skin samples were analyzed using Baker's scoring system, Masson's trichrome staining, immunohistochemistry, and real-time PCR analysis. IMQ-induced plaque-type psoriasis resulted in a significant increase (P<0.05) in dermal thickness, hyperkeratosis, PASI score, and inflammatory cytokines at the lesion site. The topical PS and cyclosporine A significantly (P<0.05) reduced PASI score and dermal thickness, while also alleviating erythema and scaling when compared to untreated mice. Furthermore, biomolecular assessments revealed that PS significantly (P<0.05) inhibited the gene expression of IL-17, IL-23, and TNF-α cytokines in the IMQ-induced lesions. Topical PS may pointedly alleviate psoriasis through the inhibition of inflammation. The beneficial effects of the PS recommend further investigation in both experimental and clinical studies in the control of skin psoriasis.

Application of Box-Behnken design for the optimization of Khellin-loaded ethosomes formulation for the management of psoriasis in mice

The objective of the present study was to develop and optimize Khellin-loaded ethosomes formulation to enhance the topical delivery of Khellin for the management of psoriasis. Based on vesicle size, polydispersity (PdI) and encapsulation efficiency, the formulation was optimized using the "3-factor 3-level", Box-Behnken design (BBD). Antioxidant, Anti-inflammatory and Anti-psoriatic activity were further assessed for the optimized formulation. The optimized formulation carried vesicles with a size of 214.64 ± 0.04 nm, PdI 0.387 ± 0.001 and an encapsulation efficiency of 68.38 ± 0.01%. Rhodamine-B loaded formulation was applied to mice skin, and the penetration depth was measured using confocal laser scanning microscopy (CLSM). It was found that the Rhodamine-B solution penetrated mice’s skin to a depth of 20.0 µm. However, the Rhodamine-B loaded ethosomes formulation penetrated mice’s skin to a depth of 55.0 µm. Further, the Khellin-loaded ethosomes formulation possessed strong antioxidant activity, presented a good reduction in paw edema, and showed good anti-inflammatory activity. In addition, the prepared Khellin-loaded ethosomes formulation exhibited considerable effects against psoriasis.

Modulation of Plet1 expression by N-Acetylglucosamine through the IL-17A-MAPK pathway in an imiquimod-induced psoriasis mouse model.

Psoriasis (Ps) is a chronic inflammatory disorder marked by skin plaque formation, driven by immune dysregulation and genetic factors. Despite the available treatments, incidence of Ps is increasing in the dermatology patients. Novel strategies are crucial due to current treatment limitations. The interleukin 17 (IL-17) pathway is pivotal in Ps pathogenesis, however the expression of its putative target gene placenta expressed transcript 1 (Plet1) remains unstudied in Ps. Considering the potential anti-inflammatory properties of N-Acetylglucosamine (GlcNAc), our study explored its role in modulating Plet1 expression in an imiquimod (IMQ)-induced Ps mouse model. Our data demonstarted a significant reduction of inflammation and Psoriasis Area and Severity Index (PASI) scores, downregulation of growth factors (GFs), IL-17A, and MAPK expression after GlcNAc treatment. In addition, GlcNAc treatment reduced neutrophils, monocyte-dendritic cells (Mo-DC) and conventional T cells (Tcons) while increasing monocyte-macrophages (Mo-Macs) and regulatory T cells (Tregs). GlcNAc treatment also downregulated Plet1 overexpression in psoriatic mouse skin and in vitro, reduced proliferation and apoptosis in IL-17A stimulated human dermal fibroblasts (HDF), along with IL-17A and TGF-β mRNA expression. Together, these data suggest that, GlcNAc interferes with downstream mechanisms in IL-17 pathway and downregulating Plet1 expression, presenting a promising strategy for Ps treatment.

Efficient Treatment of Psoriasis Using Conditioned Media from Mesenchymal Stem Cell Spheroids Cultured to Produce Transforming Growth Factor-β1-Enriched Small-Sized Extracellular Vesicles.

Psoriasis is a common chronic inflammatory disease in which keratinocytes proliferate abnormally due to excessive immune action. Psoriasis can be associated with various comorbidities and has a significant impact on health-related quality of life. Although many systemic treatments, including biologic agents, have been developed, topical treatment remains the main option for psoriasis management. Consequently, there is an urgent need to develop topical treatments with minimal side effects and high efficacy. Mesenchymal stem cells (MSCs) exhibit excellent immune regulation, anti-inflammatory activities, and therapeutic effects, and MSC-derived extracellular vesicles (EVs) can serve as crucial mediators of functional transfer from MSCs. Therefore, this study aimed to develop a safe and easy-to-use emulsion cream for treating psoriasis using MSC conditioned media (CM) containing EVs. We developed an enhanced Wharton's jelly MSC (WJ-MSC) culture method through a three-dimensional (3D) culture containing exogenous transforming growth factor-β3. Using the 3D culture system, we obtained CM from WJ-MSCs, which yielded a higher EV production compared to that of conventional WJ-MSC culture methods, and investigated the effect of EV-enriched 3D-WJ-MSC-CM cream on psoriasis-related inflammation. Administration of the EV-enriched 3D-WJ-MSC-CM cream significantly reduced erythema, thickness, and scaling of skin lesions, alleviated imiquimod-induced psoriasiform lesions in mice, and ameliorated histopathological changes in mouse skin. The upregulated mRNA expression of inflammatory cytokines, including IL-17a, IL-22, IL-23, and IL-36, decreased in the lesions. In conclusion, we present here a new topical treatment for psoriasis using an MSC EV-enriched cream.

Reveal mechanical and optical properties changes during prolonged skin stretching via in vivo continuous investigation

Skin expansion is a well-established technique in plastic surgery, and recent studies have highlighted its potential in promoting hair regeneration. This study aimed to explore how the mechanical and optical properties of skin change during a prolonged stretching process. A hybrid method was developed to assess, in vivo, the effects of an 8-day skin stretching protocol—previously used in hair regeneration research—on the dorsal skin of mice. This method combined mechanical and optical measurement systems. Tensile stress–strain curves were generated using a spring-based setup, while optical properties such as scattering and birefringence were analyzed with a polarimetry imaging system that incorporated the Mueller matrix (MM) and Mueller matrix polar decomposition (MMPD) methods. The results showed that Young's modulus increased from approximately 5 kPa on day 1 to 60–100 kPa by days 6–8, indicating collagen fiber straightening and increased stiffness. Optical analysis revealed greater anisotropy in both scattering and birefringence, as reflected by changes in MM elements and MMPD results. These changes suggest skin adaptation and regeneration, particularly within the first 24 h of stretching. Interestingly, alterations in optical properties closely mirrored changes in mechanical properties, pointing to a coordinated process of structural remodeling and functional adaptation in the skin. These findings offer valuable insights into skin remodeling and adaptation, which could guide future tissue engineering strategies.

Targeting hypoxia and thrombospondin-2 in diabetic wound healing.

Impaired wound healing in diabetic patients is the leading cause of diabetes-associated hospitalizations and approximately 50% of lower limb amputations. This is due to multiple factors, including elevated glucose, sustained hypoxia, and cell dysfunction. Previously, diabetic wounds were found to contain excessive levels of the matricellular protein thrombospondin-2 (TSP2) and genetic ablation of TSP2 in diabetic mice or treatment of wounds with a hydrogel derived from TSP2-null mouse skin improved healing. Previously, TSP2 has been shown to be repressed by hypoxia, but in the present study we observed sustained hypoxia and overlapping TSP2 deposition in diabetic wounds. We determined this observation was due to the insufficient HIF-1α activation verified by western blot and immunofluorescent analysis of wound tissues and invitro hypoxia experiments. Application of Dimethyloxalylglycine (DMOG), which can stabilize HIF-1α, inhibited TSP2 expression in diabetic fibroblasts in hypoxic conditions. Therefore, we prepared DMOG-containing TSP2KO hydrogel and applied it to the wounds of diabetic mice. In comparison to empty TSP2KO hydrogel or DMOG treatment, we observed improved wound healing associated with a reduction of TSP2, reduced hypoxia, and increased neovascularization. Overall, our findings shed light on the intricate interplay between hyperglycemia, hypoxia, and TSP2 in the complex environment of diabetic wounds.

Protective Effects of Keratinocyte-Derived GCSF and CCL20 on UVB-Induced Melanocyte Damage.

The skin microenvironment created by keratinocytes (KC) influences the stress responses of melanocytes (MC) to UVB insults. This study employed RNA sequencing analysis as well as in vitro and in vivo models to elucidate the underlying mechanisms. Our RNA-Seq analysis revealed a statistically significant upregulation of GCSF and CCL20 genes in UVB-irradiated KC, correlating with the protective effects of KC on MC responses to UVB exposure. Recombinant GCSF and CCL20 exhibited the most pronounced modulation of UVB-induced MC responses. These effects included the attenuation of apoptosis and reduction of ROS formation, along with the upregulation of tyrosinase and tyrosinase-related protein-1, which are involved in the melanogenic pathway. ELISA was also used to confirm that UVB could induce the secretion of GCSF and CCL20 from KC. A similar correlation between GCSF and CCL20 expression in KC and tyrosinase levels in MC was observed in UVB-irradiated mouse skin. Our study provides novel insights into the protective role of GCSF and CCL20 in the paracrine effects of KC on UVB-induced MC damage through the modulation of stress response pathways, the MITF-tyrosinase axis, and the regulation of p53. These findings have implications for the development of pharmacological strategies targeting KC-derived paracrine factors for the prevention of skin photodamage.

Application of a Photothermal Microscope To Study the Process of Cutaneous Lesion Formation of Malignant Melanoma.

In this study, we applied a photothermal microscope to study the process of malignant melanoma formation. We analyzed benign papilloma tumors, their metastatic carcinomas, and metastatic melanoma on the preparation of mouse skin using a gray-level co-occurrence matrix (GLCM) method. Based on the analysis of nine GLCM parameters investigated, the characteristics during the degenerative and metastatic processes are clarified by the investigation. The determination of characteristic parameters corresponding to three processes before, during, and after the degeneration indicated that this investigation enables the detection of the malignant transformation and related processes.

Senescent cell transplantation into the skin induces age-related peripheral dysfunction and cognitive decline.

Cellular senescence is an established cause of cell and tissue aging. Senescent cells have been shown to increase in multiple organs during aging, including the skin. Here we hypothesized that senescent cells residing in the skin can spread senescence to distant organs, thereby accelerating systemic aging processes. To explore this hypothesis, we initially observed an increase in several markers of senescence in the skin of aging mice. Subsequently, we conducted experiments wherein senescent fibroblasts were transplanted into the dermis of young mice and assessed various age-associated parameters. Our findings reveal that the presence of senescent cells in the dermal layer of young mice leads to increased senescence in both proximal and distal host tissues, alongside increased frailty, and impaired musculoskeletal function. Additionally, there was a significant decline in cognitive function, concomitant with increased expression of senescence-associated markers within the hippocampus brain area. These results support the concept that the accumulation of senescent cells in the skin can exert remote effects on other organs including the brain, potentially explaining links between skin and brain disorders and diseases and, contributing to physical and cognitive decline associated with aging.