A Single-Cell Transcriptomic Atlas of Human Skin Aging

Area of Science:

• Dermatology
• Molecular Biology
• Gerontology

Background:

• Human skin aging is characterized by functional decline and visible changes.
• Understanding the molecular and cellular basis of skin aging is crucial for developing interventions.
• Previous studies have not fully elucidated the single-cell landscape of aging human skin.

Purpose of the Study:

• To investigate the molecular and cellular changes in human eyelid skin during aging using single-cell RNA sequencing.
• To identify key transcription factors and cellular pathways involved in skin aging.
• To explore potential therapeutic targets for age-related skin disorders.

Main Methods:

• Single-cell RNA sequencing of human eyelid skin from individuals across different age groups.
• Bioinformatic analysis to identify cell types, subpopulations, and transcriptional changes.
• Functional assays to assess the impact of transcription factor inhibition and activation on cellular processes.

Main Results:

• Eleven canonical cell types and six basal cell subpopulations were identified in aging human skin.
• Progressive accumulation of photoaging signatures and chronic inflammation were observed with age.
• Early-onset decline in developmental transcription factors was noted, with HES1 and KLF6 playing critical roles.
• Inhibition of HES1 and KLF6 led to impaired cell proliferation, increased inflammation, and senescence.
• Genetic activation of HES1 or quercetin treatment reduced dermal fibroblast senescence.

Conclusions:

• Single-cell analysis provides a molecular framework for understanding human skin aging.
• Transcription factors HES1 and KLF6 are critical regulators of skin cell homeostasis during aging.
• Targeting these transcription factors or using compounds like quercetin may offer therapeutic strategies for skin aging and related disorders.