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Omics · study · 2026

Age-related changes in the phenotype and function of mouse skin macrophages

Listed in NCBI GEO

Skin ageing is accompanied by chronic low-grade inflammation (“inflammaging”) and progressive remodelling of the dermal extracellular matrix, yet the cellular changes that initiate these processes early in life remain poorly defined.

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Here we used single-cell RNA sequencing (scRNA-seq) of dorsal skin from young (8-week), middle-aged (26-week) and aged (52-week) male C57BL/6 mice to map age-related shifts in cellular composition, with a focus on macrophages.

Whereas the relative proportions of most cell types remained largely stable, the macrophage compartment expanded markedly in the oldest skin. Sub-clustering resolved four macrophage populations, three of which expanded or emerged with age. The Mac4 population, marked by S100a8 and S100a9 and a Cd14-high monocyte-derived signature, was detected only in aged skin and was confirmed in situ by F4/80, S100a8 and S100a9 co-staining.

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Cell–cell communication analysis predicted increased macrophage-to-fibroblast signalling in aged skin, including the pro-fibrotic mediators Thbs1 and Spp1, accompanied by up-regulation of collagen and fibrosis-associated genes in a subset of fibroblasts (FB3/FB4). Notably, collagen transcripts increased while COL5A3 protein decreased and dermal collagen architecture appeared disorganised by second-harmonic-generation imaging, pointing to post-transcriptional control of matrix remodelling.

Ex vivo treatment of aged skin with the secretome of γ-irradiated peripheral blood mononuclear cells (PBMC-sec) reduced the macrophage expansion towards a more youthful composition and down-regulated fibrosis-associated fibroblast genes. Together, these findings identify the early emergence of monocyte-derived, pro-inflammatory and potentially pro-fibrotic macrophage subsets as a feature of mouse skin ageing and suggest that PBMC-sec can partially counteract these changes.

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Life Sciences
Inferred from text
Imaging 75% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 11 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE33640015 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:imagingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:single-cell-rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title