Disrupted mitochondrial function in aged human dermal fibroblasts
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ABSTRACT:
PROVIDER: PRJNA545351 | ENA |
REPOSITORIES: ENA
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Project description:Skin undergoes changes in structure and function with age, including a shift in metabolic programs. This is particularly evident relative to mitochondrial function in skin cells. Dermal fibroblasts have been known to accumulate damage caused by both external and internal stressors, leading to altered bioenergetics that limits efficient synthesis of ATP and NAD+. To better understand the changes in mitochondrial function with age, metabolic profiles and transcriptomic profiles of primary dermal fibroblasts from varying aged donors were analysed.
2020-10-26 | GSE131938 | GEO
Project description:Extrinsic skin ageing converges on the dermis, a post-mitotic tissue compartment consisting of extracellular matrix and long-lived fibroblasts prone to damage accumulation and maladaptation. Aged human fibroblasts exhibit mitochondrial and nuclear dysfunctions, but it is unclear whether these are cause or consequence of ageing. We report on a systematic study of human dermal fibroblasts retrieved from female donors aged 20-67 years and analyzed in primary culture at low population doubling precluding replicative senescence. Genome-wide array analysis failed to detect significant (>2-fold) age-related expression changes for individual genes, but gene set enrichment analysis revealed down regulation of many genes involved in mitochondrial metabolism and respiratory electron transport, extracellular matrix maintenance, cell cycle progression and protein translation. Consistent with these changes, mitochondrial content, respiratory function and cell proliferation declined with donor age. This was associated with inadequate nuclear mito-biogenesis, hypo- phosphorylation of AMP-dependent protein kinase alpha and upregulation of the alpha2-isoform, suggesting that inadequate mito-nuclear signalling could be the leading event entailing decreased expression of mitochondrial genes and compensatory down regulation of proliferation and protein synthesis. The comparatively few genes exhibiting age-associated up regulation were associate with cholesterol metabolism, immune reactions and mRNA processing, possibly also reflecting adaptation to inadequate mitochondrial function. Donors: 15 human female donors included in the study were aged 20, 21, 23, 26, 26, 40, 41, 42, 43, 49, 60, 62, 63, 64 and 67 years, thus covering the age spectrum 20 – 67 years and providing five biological replicates for each of the age groups “young” (20-30 years), “middle” (40-50 years) and “old” (60-70 years). Human dermal fibroblasts were isolated from skin specimen removed in the course of cosmetic surgery from the bottom side of female breast. Isolation and primary culture of the cells followed published procedures (Tigges and others 2013). Cells were not expanded beyond 12 population doublings, while replicative cell cycle arrest was determined to not occur before 40 population doublings.
2014-04-08 | E-GEOD-55118 | biostudies-arrayexpress
Project description:Mouse primary dermal fibroblasts were treated with 100 nM endothelin-1 (ET1) synthetic peptide for 24 hours. Control samples received no ET1 peptide. The experiment compared treated to untreated to identify gene expression changes due to ET1 exposure. There are three biological replicates for both control and treated samples. These biological replicates represent separate derivations of primary dermal fibroblasts from genetically identical mouse litters aged 0-3 days.
2005-01-01 | E-MEXP-700 | biostudies-arrayexpress
Project description:scRNAseq of aging dermal fibroblasts
| PRJNA435994 | ENA
Project description:The goal of this project is to compare the protein composition of the extracellular matrices (ECMs) deposited in vitro by wild type, heterozygous, or SPAG17 KO neonatal mouse dermal fibroblasts.
2022-09-22 | PXD019869 | Pride
Project description:Mouse primary dermal fibroblasts were treated with DNA demethylating agent 5-aza-2'-deoxycytidine. The exposure was 5um 5A2dC for 96 hours followed by recovery in normal medium for 24 hours. Three biological replicates were created for both the control and treated populations. Each biological replicate represents a separate derivation of dermal fibroblasts from genetically identical mouse pups aged 0-3 days. Cells reached passage 4 before initiating drug exposure.
2005-01-01 | E-MEXP-701 | biostudies-arrayexpress
Project description:Transcriptomic analysis of murine aging dermal fibroblasts at single cell level.
2018-11-14 | GSE111136 | GEO
Project description:To determine if aberrant activation of endothelin-1 (Et1) could lead to the dysregulation of many downstream genes, we exposed fibroblasts to exogenous ET1 peptide and assayed for transcriptional changes by microarray. Mouse dermal fibroblasts were treated with exogenous Et1 peptide for 24 hours. ET1 treatment resulted in significant expression changes - primarily downregulation - of a number of genes. In particular, Tgf-beta-2 and Tgf-beta-3 were among the downregulated genes, which in turn alter the expression status of their many target genes. These data suggest that the stable silencing of Et1 is important for the phenotypic stability of dermal fibroblasts, and perhaps many other cell types as well.<br><br>Three separate biological replicates were derived for both control and treated samples. The primary dermal fibroblasts were derived by explant procedure from the skin of mouse pups aged 0-3 days. By passage 5, cells were split to two separate cultures-- one with 100nM synthetic Et1 peptide added to the medium (treated) and the other with nothing added (control). Cells were exposed to Et1 for 24 hrs, then treated and control populations were harvested for total RNA.
2007-06-29 | E-GEOD-4695 | biostudies-arrayexpress
Project description:RNA-seq of of dermal fibroblasts
| PRJEB22019 | ENA
Project description:The transcriptome of murine dermal fibroblasts
| PRJNA435488 | ENA