Vitamin D receptor signaling in inflammatory senescence–associated skin aging: Mechanisms and therapeutic potentials

Vitamin D receptor (VDR) signaling plays a crucial role in skin homeostasis and represents a promising therapeutic target for inflammatory senescence-associated skin aging. This review examines the roles of VDR signaling in inflammatory senescence-associated skin aging. We summarize the actions of VDR through chromatin modification, transcriptional regulation, and coregulator recruitment, which collectively modulate inflammation and cellular senescence in aging skin. Recent findings highlight the protective role of VDR against inflammatory responses and aging processes through multiple pathways, including NF-κB suppression and regulation of senescence-associated pathways. The review discusses cell-type specific VDR regulation in keratinocytes, immune cells, dermal fibroblasts, and stem cells, emphasizing their distinct roles in skin homeostasis. Current therapeutic approaches encompass vitamin D-based treatments, traditional medicine-derived bioactive compounds, and novel drug delivery systems. Research challenges include limitations in monitoring VDR activity in aging skin and developing effective tissue-specific delivery methods. This analysis emphasizes the therapeutic potential of VDR modulation in aging-related skin conditions and highlights priorities for future investigation of VDR-mediated regulation in inflammatory senescence-associated skin diseases.