Circadian Rhythms in Dermatology: Mechanisms, Clinical Implications, and Chronotherapy Opportunities.

OBJECTIVE

Circadian rhythms regulate key cutaneous processes including DNA repair, keratinocyte proliferation, wound healing, and immune responses. Disruption of circadian timing contributes to photoaging, inflammatory dermatoses, nocturnal pruritus, and carcinogenesis. This review synthesizes current evidence and highlights translational opportunities, aiming to bridge molecular insights with clinical dermatology.

DATA SOURCES: A literature search was conducted in PubMed, Scopus, and Web of Science from January 1990 to March 2025 using terms such as "circadian rhythm," "clock genes," "chronotherapy," "skin," "dermatology," "photoaging," "melatonin," "vitamin D," "psoriasis," "pruritus," and "skin cancer."

STUDY SELECTION: Of 360 records identified, 101 unique publications remained after duplicate removal. Fifty-two were excluded after abstract review. Forty-nine full texts were assessed, and 39 met the inclusion criteria.

DATA EXTRACTION: Studies relevant to circadian regulation of skin physiology, dermatologic conditions, and therapeutic implications were included. Human, animal, and in vitro studies were analyzed, with emphasis on translational findings.

DATA SYNTHESIS: Circadian genes (CLOCK, BMAL1, PER, CRY) regulate epidermal renewal, pigmentation, and repair. DNA repair peaks during the active phase, whereas ultraviolet exposure in the rest phase increases mutagenesis. Melatonin and vitamin D metabolites enhance photoprotection and regeneration. Clinical conditions, including psoriasis, nocturnal itch, and skin cancer, are influenced by circadian misalignment, especially in shift workers. Preliminary evidence suggests that aligning therapies with circadian timing may improve efficacy and reduce toxicity.

CONCLUSIONS

Circadian biology provides a unifying framework for skin physiology and disease. Chronotherapy and biomarker-guided approaches represent promising strategies, but translation into practice requires validation in large, well-designed trials.