Investigating Transcriptional Age Acceleration in Inflammatory Skin Diseases

Area of Science:

• Dermatology and Molecular Biology
• Genetics and Epigenetics
• Aging Research

Background:

• Epigenetic age acceleration is known in inflammatory skin disease.
• Transcriptional clocks, representing age-related gene expression, are less understood in these conditions.

Purpose of the Study:

• To investigate the role of transcriptional clocks in hidradenitis suppurativa, atopic dermatitis, and plaque psoriasis.
• To understand the pathophysiology and disease trajectory of these inflammatory skin conditions.

Main Methods:

• Utilized 7 clock algorithms to analyze gene expression in patients (n=37 hidradenitis suppurativa, n=27 atopic dermatitis, n=28 plaque psoriasis) and healthy subjects (n=38).
• Compared transcriptional age between lesional, nonlesional, and healthy skin.
• Analyzed associations between FLG gene variants and transcriptional age acceleration in atopic dermatitis.

Main Results:

• Five of 7 transcriptional clocks accurately predicted age across all groups.
• Significant age acceleration was observed in lesional skin compared to healthy and nonlesional skin for all studied diseases.
• FLG gene variants correlated with transcriptional age acceleration in atopic dermatitis patients.
• Clock genes were enriched in pathways related to aging, inflammation, and metabolism.

Conclusions:

• Transcriptional age acceleration is evident in inflammatory skin diseases.
• These findings provide a foundation for exploring age-related transcriptional changes in skin disease pathophysiology.
• Transcriptional clocks may offer insights into disease trajectory and aging processes in the skin.