An Improved Human 3D Skin Model for Aging Research
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ABSTRACT:
PROVIDER: PRJNA1238314 | ENA |
REPOSITORIES: ENA
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Project description:Current models used to study skin aging, including in vivo murine models, ex vivo human skin, and in vitro 2D cell cultures, present significant limitations in replicating the complexity of chronological human skin aging. To address this gap, we developed a novel 3D human full-thickness skin aging model using primary dermal fibroblasts and epidermal keratinocytes harvested from the same aged donors (average age 80 years). Comprehensive histological, immunostaining, and transcriptomic analyses of this aging model, compared to a young 3D skin model (average age 20 years), revealed distinct hallmarks of chronological skin aging, including reduced epidermal and dermal thickness, decreased extracellular matrix content, diminished cell proliferation, and increased cellular senescence. Furthermore, 3D aging skin model also showed reduced IGF-1 expression and induction of AP1/JunB, which were consistent with observations in aged human skin. Transcriptomic profiling further identified upregulated pathways associated with extracellular matrix degradation, cellular senescence, and immune responses, aligning closely with published data from human aged skin. This novel in vitro model faithfully recapitulates several key features of chronological skin aging, offering a robust platform for studying aging mechanisms and testing therapeutic interventions. We have used microarray to study the gene expression profile of 3D skin models
2025-03-31 | GSE292398 | GEO
Project description:Local IL-17 orchestrates skin aging
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Project description:Aging is a multifaceted systemic process that contributes to the onset of age-related diseases. Despite advances, few comprehensive anti-aging strategies have successfully reversed the adverse effects of aging. Heterochronic parabiosis studies have highlighted the potential of systemic rejuvenation through blood-borne factors, yet the precise drivers of aging and rejuvenation, along with their mechanisms, remain largely elusive. Furthermore, translating these findings to humans has been challenging. In this study, we achieved human skin rejuvenation through systemic factors using a microphysiological system comprising a 3D skin model and a 3D bone marrow model, which simulates the niche for progenitor and blood cells. Treatment with young human serum, compared to aged human serum, enhanced cell proliferation and reduced the biological age of skin tissue, as determined by methylation-based age clocks. Notably, these effects required the presence of bone marrow-derived cells in the system. Further analysis of the bone marrow model revealed serum-dependent changes in cell population composition and aging markers. Proteome profiling identified 55 potential systemic rejuvenating proteins secreted by bone marrow-derived cells. Among these, seven proteins were validated to have rejuvenating effects on human skin cells through hallmark aging assays, underscoring their role as key systemic factors in reversing skin aging.
2025-07-29 | PXD059082 | Pride
Project description:We analyze the effect of magnetic 3D bioprinting using NanoShuttle-PL on the proteome of primary human skin fibroblasts and epidermal squamous cell carcinoma cells. NanoStuttle-PL employs magnetic nanoparticles that interact electrostatically with cells rendering them magnetic and allowing manipulation of their 3D assembly using external magnetic forces.
2021-07-16 | PXD023701 | Pride
Project description:Atopic dermatitis, a chronic inflammatory skin disease with increasing prevalance, is closely associated with skin barrier defects. A cytokine related to disease severity and inhibition of keratinocyte differentiation is IL-31. To identify its molecular targets, IL-31-dependent gene expression was determined in 3-dimensional organotypic skin models. In this data set we include expression data from human 3D skin models treated with or without IL-31 for 2, 8, 24 and 48 hours. As a source of keratinocytes HaCaT cells were used. These are immortalized primary keratinocytes. Human dermal fibroblasts were derived from a skin biopsy. A total of 8 samples were analyzed. We compared the control vs the IL-31 treated sample for each time point.
2016-02-29 | E-GEOD-76880 | biostudies-arrayexpress
Project description:This study examines differential gene expression in 3D skin organoids treated with Nintedanib.
2025-02-17 | GSE289407 | GEO
Project description:Human skin is composed of the cell-rich epidermis, the extracellular matrix (ECM) rich dermis, and the hypodermis. Within the dermis, a dense network of ECM proteins provides structural support to the skin and regulates a wide variety of signaling pathways which govern cell proliferation and other critical processes. Both intrinsic aging, which occurs steadily over time, and extrinsic aging (photoaging), which occurs as a result of external insults such as UV radiation, cause alterations to the dermal ECM. In this study, we utilized both quantitative and global proteomics, alongside single harmonic generation (SHG) and two-photon autofluorescence (TPAF) imaging, to assess changes in dermal composition during intrinsic and extrinsic aging. We find that both intrinsic and extrinsic aging result in significant decreases in structural ECM integrity, evidenced by decreasing collagen abundance and increasing fibril fragmentation, and ECM-supporting proteoglycans. Intrinsic aging also produces changes distinct from those produced by photoaging, including reductions in elastic fiber and crosslinking enzyme abundance. In contrast, photoaging is primarily defined by increases in elastic fiber-associated protein and pro-inflammatory proteases. Changes induced by photoaging are evident even in comparisons of young underarm and forearm skin, indicating that photoexposure experienced by an individual’s mid-20s is sufficient for large-scale proteomic alterations and that molecular-level changes due to photoaging are evident well before clinical indications are present. GO term enrichment revealed that both intrinsic aging and photoaging share common features of chronic inflammation.
2020-07-03 | PXD015982 | Pride
Project description:Age-related cognitive decline is associated with altered physiology of the hippocampus. While changes in gene expression have been observed in aging brain, the regulatory mechanisms underlying these changes remain underexplored. We generated single-nucleus gene expression, chromatin accessibility, DNA methylation, and 3D genome data from 40 human hippocampal tissues spanning adult lifespan. We observed a striking loss of astrocytes, OPC, and endothelial cells during aging, including astrocytes that play a role in regulating synapses. Microglia undergo a dramatic switch from a homeostatic state to a primed inflammatory state through DNA methylome and 3D genome reprogramming. Aged cells experience erosion of their 3D genome architecture. Our study identifies age-associated changes in cell types/states and gene regulatory features that provide insight into cognitive decline during human aging.
2025-06-10 | GSE299139 | GEO
Project description:Skin aging is characterized by structural and functional changes that lead to slower wound healing and higher rate of infections, which contribute to age-associated frailty. This likely depends on synergy between alterations in the local microenvironment and stem cell–intrinsic changes, underscored by pro-inflammatory microenvironments that drive pleotropic changes. To date, little is known about the precise nature and origin of the proposed age-associated inflammatory cues, or how they affect different tissue resident cell types. Based on deep single-cell RNA-sequencing of the entire dermal compartment, we now provide a comprehensive understanding of the age-associated changes in all skin cell types. We show a previously unreported skew towards an IL-17–expressing phenotype of Th cells, γδ T cells and innate lymphoid cells in aged skin. Aberrant IL-17 signaling is common to many autoimmune (e.g., rheumatoid arthritis and psoriasis) and chronic inflammatory diseases. Importantly, in vivo blockade of IL-17–triggered signaling during the aging process reduces the pro-inflammatory state by affecting immune and non-immune skin cells of both dermis and epidermis. Strikingly, IL-17 neutralization significantly delays the appearance of age-related traits, such as decreased epidermal thickness, increased cornified layer thickness and ameliorated hair follicle stem cell activation and hair shaft regeneration. Our results indicate that the aged skin shows chronic and persistent signs of inflammation, and that age-associated increased IL-17 signaling could be targeted as a strategy to prevent age-associated skin ailments in elderly.
2022-12-31 | GSE193920 | GEO
Project description:Organismal aging in mammals is manifested with architectural alteration and functional decline of multiple organs throughout the body. In aged skin, hairs are sparse, which has led to the hypothesis that the hair follicle stem cells (HFSCs) undergo epidermal differentiation during aging. Here, we employ single cell analysis to interrogate aging-related changes in the HFSCs. Unexpectedly, HFSCs maintain their lineage fidelity and show no signs of shifting to an epidermal fate. Despite maintaining lineage identity, HFSCs do show prevalent transcriptional changes in extracellular matrix genes. Of importance, these HFSC changes are accompanied by profound architectural perturbations in the aging stem cell niche. Upon surveying the dermis from young and aged skin, we also observe age-related changes in many non-epithelial cell types, including resident immune cells, sensory neurons, arrector pili muscles, and blood vessels – all of which have been previously associated with abilities to modulate hair follicle regeneration. Consistent with both intrinsic and extrinsic alterations in stem cell: niche communications, we find that in response to skin wounding, aged HFSCs repair the epidermis, but are defective in hair follicle regeneration. Intriguingly, whereas aged dermis cannot support young HFSCs, aged HFSCs can be rescued when supported by young dermis. Together, these findings favor a model where skin tissue microenvironment plays a dominant role in dictating the molecular properties and activities of HFSCs.
2019-12-31 | GSE124901 | GEO