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- W4366183963 abstract "Normal aging is associated with progressive changes in cellular function. Keratinocytes experience continual cycles of cellular division and renewal as well as constant exposure to external stimuli, while the balance between unperturbed aging and the cumulative effects of environmental exposures are not completely defined. We isolated keratinocytes from 12 mice aged 3-86 weeks and found 876 differentially methylated regions by whole genome bisulfite sequencing, with regions of progressive DNA hypo/hyper-methylation with age, suggesting a gradual programmatic or population shift in these cells. We found no major population shifts defined by flow cytometry immunophenotyping of murine epidermis. To define programmatic alterations, we performed single cell RNA sequencing on epidermal cells isolated from 10 C57Bl/6 mice ranging from 3-105 weeks of age. We analyzed 66,096 keratinocyte transcriptomes, revealing a distinct aging signature in 6.2% of basal interfollicular keratinocytes in 3wk old mice that increased to 85.4% in >100wk old mice, while other populations like the follicle bulge and upper hair follicle remained relatively stable. We validated aging marker expression using western blot and CITE-seq and found that aging-associated signatures were preserved in lymphocyte-deficient NSG-SGM3 mice, demonstrating that the aging phenotype is independent of mouse strain and immune aging. Gene set enrichment comparing gene expression between aged and young basal interfollicular keratinocytes revealed multiple pathway alterations including activation of inflammatory and hypoxia signaling pathways, as well as an inverse relationship between oxidative phosphorylation and glycolytic pathway gene expression with age. Finally, the murine-derived aging signature was elevated in aged compared to young skin from the GTEx human transcriptome dataset (n=1305) and was independent of sex or sun exposure, suggesting these pathways may be relevant to human skin intrinsic aging." @default.
- W4366183963 created "2023-04-19" @default.
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- W4366183963 date "2023-05-01" @default.
- W4366183963 modified "2023-09-28" @default.
- W4366183963 title "1340 Basal keratinocytes exhibit age-related epigenetic and transcriptomic alterations resulting in an altered metabolic profile" @default.
- W4366183963 doi "https://doi.org/10.1016/j.jid.2023.03.1356" @default.
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