Vitamin D and the aging skin: insights into oxidative stress, inflammation, and barrier function.

Abstract

Skin aging is a multifactorial biological process driven by the cumulative effects of oxidative stress, chronic low-grade inflammation, and progressive deterioration of barrier function. Among its pivotal regulatory nodes, the Vitamin D-Vitamin D receptor (VDR) signaling axis acts as an integrative hub that senses and coordinates photic, redox, and metabolic cues to regulate immune homeostasis and structural integrity, thereby shaping the skin's defensive and reparative capacity throughout aging. Disruption of this axis amplifies inflammaging, accelerates dermal and epidermal structural decline, and compromises cutaneous resilience against environmental insults. Phenotypic shifts in keratinocytes, melanocytes, Langerhans cells, and T lymphocytes during aging are tightly linked to VDR-governed transcriptional programs and pathway crosstalk. Mechanistically, Nrf2-mediated antioxidant networks, Wnt/β-catenin and NF-κB signal interplay, stabilization of E-cadherin/β-catenin complexes, lipid metabolic remodeling, and reprogramming of immune tolerance collectively constitute the molecular basis through which Vitamin D mitigates skin aging. This review systematically delineates the critical role of the VDR axis in the onset and progression of skin aging and proposes its repositioning as a programmable molecular node for intervention, aiming to modulate inflammaging and maintain barrier homeostasis to slow the structural and functional decline of aging skin.