The Impact of Vitamin D on Skin Aging

The active metabolites of vitamin D₃ (D₃) and lumisterol (L₃) exert a variety of antiaging and photoprotective effects on the skin. These are achieved through immunomodulation and include anti-inflammatory actions, regulation of keratinocytes proliferation, and differentiation programs to build the epidermal barrier necessary for maintaining skin homeostasis. In addition, they induce antioxidative responses, inhibit DNA damage and induce DNA repair mechanisms to attenuate premature skin aging and cancerogenesis. The mechanism of action would involve interaction with multiple nuclear receptors including VDR, AhR, LXR, reverse agonism on RORα and -γ, and nongenomic actions through 1,25D₃-MARRS receptor and interaction with the nongenomic binding site of the VDR. Therefore, active forms of vitamin D₃ including its canonical (1,25(OH)₂D₃) and noncanonical (CYP11A1-intitated) D₃ derivatives as well as L₃ derivatives are promising agents for the prevention, attenuation, or treatment of premature skin aging. They could be administrated orally and/or topically. Other forms of parenteral application of vitamin D₃ precursor should be considered to avoid its predominant metabolism to 25(OH)D₃ that is not recognized by CYP11A1 enzyme. The efficacy of topically applied vitamin D₃ and L₃ derivatives needs further clinical evaluation in future trials.