HOXC10 Protects from Skin Aging by Targeting the FZD6/Wnt/β-Catenin Signaling Pathway

Area of Science:

• Molecular Biology
• Gerontology
• Dermatology

Background:

• Aging involves complex gene regulation, with transcription factors playing a crucial role.
• Skin aging is characterized by a decline in cellular function and tissue integrity.

Purpose of the Study:

• To identify core regulatory elements in the transcription factor network of skin aging.
• To investigate the role of homeobox C10 (HOXC10) in the aging process.
• To explore potential therapeutic strategies for delaying skin aging.

Main Methods:

• Single-cell transcriptome analysis of skin.
• In vivo and in vitro experiments using senescent fibroblasts and aging tissues.
• Mechanistic studies involving gene expression analysis and pathway activation.
• Connectivity Map approach to identify functional mimics.

Main Results:

• HOXC10 was identified as a core transcription factor in skin aging.
• HOXC10 expression was decreased in senescent fibroblasts and aging skin.
• Overexpression of HOXC10 delayed cellular senescence and skin aging.
• HOXC10 reduced FZD6 expression, activating the Wnt/β-catenin pathway.
• Simvastatin was identified as a functional mimic of HOXC10 with anti-aging effects.

Conclusions:

• HOXC10 plays a critical role in regulating skin aging through the FZD6/Wnt/β-catenin signaling pathway.
• Targeting the HOXC10/FZD6 axis presents a potential therapeutic strategy for skin aging.
• Simvastatin demonstrates potential as an anti-aging agent for skin.