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

Area of Science:

• Biogerontology
• Dermatology
• Molecular Biology

Background:

• Cellular senescence is a key aging mechanism, but tissue-specific differences necessitate tailored detection methods.
• Existing senescence gene sets lack specificity for skin, limiting their effectiveness in dermatological research.
• Heterogeneity in senescent cell phenotypes across tissues underscores the need for specialized gene expression profiles.

Purpose of the Study:

• To curate and validate a human skin-specific gene set for cellular senescence detection.
• To assess the efficacy of the new gene set in identifying senescence in chronological and photoaging skin.
• To compare the performance of the skin-specific gene set against commonly used, non-tissue-specific senescence markers.

Main Methods:

• Literature review and expert curation to develop the SenSkin™ gene set.
• Pathway analysis to characterize the gene set's biological relevance.
• Validation using bulk and single-cell RNA sequencing datasets from aged and photoaged skin samples.

Main Results:

• SenSkin™ primarily comprises genes associated with the senescence-associated secretory phenotype (SASP), metabolism, and immune responses.
• The gene set demonstrated higher enrichment in chronologically aged skin compared to existing senescence and aging gene sets.
• SenSkin™ showed significant upregulation in ten different skin cell types affected by photoaging in single-cell RNA-seq analysis.

Conclusions:

• SenSkin™ is a validated, human skin-specific gene set for detecting cellular senescence.
• This specialized tool shows enhanced effectiveness in identifying senescent cells in skin undergoing chronological aging and photoaging.
• SenSkin™ offers a more precise approach to studying skin aging and senescence compared to generic gene sets.