O22 Transcriptional differences in intrinsic skin ageing reveal divergent gene expression profiles in skin at the extremes of the pigmentary spectrum
Bezaleel Mambwe, Michael Peake, Clare O’Connor, Mike Bell, Mark Farrar, Abigail LangtonAbstract
Introduction and aims
Intrinsic skin ageing involves gradual structural and functional decline driven by time-dependent biological processes. While these features are well characterized in light skin, less is known about intrinsic ageing in darker skin, where clinical phenotypes appear later and differ in presentation. The transcriptional basis for these pigmentation-related differences remains poorly defined. This study applied spatial transcriptomics to characterize intrinsic ageing-related gene expression at the extremes of the pigmentary spectrum and determine whether ageing mechanisms converge between groups.
Methods
Photoprotected buttock biopsies were collected from young (22–29 years) and older (> 69 years) adults with dark (young n = 3; old n = 3) and light (young n = 3; old n = 3) individual typology angle skin types. Dark-skinned participants were of African American ancestry, and light-skinned participants were of White Northern European ancestry. Cryosections were profiled on the Xenium In Situ platform (10x Genomics) using a 475-gene custom panel. Differentially expressed genes (DEGs) were defined as > 1 log2 fold change with adjusted P < 0.05.
Results
Intrinsic ageing produced distinct transcriptional signatures in dark and light skin, with no overlapping DEGs. Dark skin showed 10 DEGs, primarily downregulation of collagen-associated genes (COL1A1, SPARC, LUM) within dermal fibroblasts. Light skin exhibited 23 DEGs, characterized by transcriptional upregulation of elastic fibre–related genes (FBLN2, FBN1, MFAP4, FBLN5, MFAP5) also localized to dermal fibroblasts, alongside reduced expression of melanocyte-associated transcripts. Cell-proportion analysis revealed diminished melanocyte abundance specifically in aged light skin.
Conclusions
These findings demonstrate that intrinsic ageing is defined by divergent transcriptional pathways in light and dark skin, rather than a shared molecular phenotype. Dark skin is characterized by reduced fibroblast-mediated collagen transcription, whereas light skin shows fibroblast-driven elastic fibre remodelling and loss of melanocyte-related transcription, indicating different biological vulnerabilities. These transcriptional distinctions underscore the importance of accounting for pigmentation when interpreting intrinsic ageing biology and developing targeted strategies to support long-term skin health.