Mapping epidermal and dermal cellular senescence in human skin aging

Area of Science:

• Dermatology
• Cell Biology
• Aging Research

Background:

• Cellular senescence, characterized by irreversible cell cycle arrest, accumulates with age due to various stressors.
• Understanding cellular senescence is crucial for investigating human skin aging and regeneration processes.

Purpose of the Study:

• To investigate epidermal and dermal senescence in human skin aging using single-cell RNA sequencing and spatial transcriptomics.
• To identify the role of senescent melanocytes and fibroblasts in age-related skin changes, particularly photoaging.

Main Methods:

• Utilized single-cell RNA sequencing and spatial transcriptomics to create a skin aging atlas.
• Curated a skin-specific cellular senescence gene set (SenSkin™) and analyzed its expression.
• Examined senescent cell distribution and their impact on epidermal and dermal cell functions.

Main Results:

• Photoaging significantly increases senescent cell burden compared to chronological aging.
• The SenSkin™ gene set is elevated in photoaged, chronologically aged, and CDKN1A+ (p21) cells.
• Senescent melanocytes increase melanin synthesis, while senescent fibroblasts decrease collagen and elastic fiber production.
• Senescent cells tend to cluster, especially in photoaged skin.

Conclusions:

• Cellular senescence is a key driver of age-related skin dysfunction, with distinct roles for epidermal and dermal senescent cells.
• Senescent melanocytes and reticular dermal fibroblasts contribute to haphazard pigmentation and reduced skin elasticity, respectively.
• This study provides a framework for understanding skin aging through the lens of cellular senescence.