SenSkin™: a human skin-specific cellular senescence gene set

Cellular senescence gene sets have been leveraged to overcome the inadequate sensitivity or specificity of single markers. However, growing evidence of heterogeneity among tissues in senescent cell phenotypes and gene expression profiles has highlighted the need for tissue-specific gene sets. SenSkin™ was curated by an expert review of literature on cellular senescence in the skin and characterized with pathway analysis. To validate SenSkin™, it was evaluated for enrichment with chronological aging in a bulk RNA-sequencing (RNA-seq) dataset and a pseudobulk RNA-seq dataset. Further, changes to SenSkin™ in different skin cell types with photoaging were evaluated in two single-cell RNA-seq datasets. SenSkin™ predominantly included genes related to the senescence-associated secretory phenotype (SASP), which were associated with metabolism and multiple aspects of immune responses. SenSkin™ was more enriched in chronologically aged skin than other commonly used cellular senescence and aging gene sets. In scRNA-seq, SenSkin™ displayed significant upregulation due to photoaging in ten skin cell types. In conclusion, SenSkin™ is a human skin-specific senescence gene set validated in chronological aging and photoaging, which may be more effective at detecting senescent cells in the skin than non-tissue-specific gene sets.