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Objectives  Although the effect of ultraviolet radiation ( UVR ) on human skin has been extensively studied, very little is known on how  UVR  impacts on hair follicle ( HF ) homeostasis. Here, we investigated how solar spectrum  UVR  that hits the human skin surface impacts on  HF  biology, and whether any detrimental effects can be mitigated by a widely used cosmetic and nutraceutical ingredient, caffeine.    Methods  Human scalp skin with terminal  HF s was irradiated transepidermally  ex vivo  using either 10 J/cm 2   UVA  (340–440 nm) + 20  mJ /cm 2   UVB  (290–320 nm) (low dose) or 50 J/cm 2   UVA  + 50  mJ /cm 2   UVB  (high dose) and organ‐cultured under serum‐free conditions for 1 or 3 days. 0.1% caffeine (5.15 mmol/L) was topically applied for 3 days prior to  UV  exposure with 40 J/cm 2   UVA  + 40  mJ /cm 2   UVB  and for 3 days after  UVR . The effects on various toxicity and vitality read‐out parameters were measured in defined skin and  HF  compartments.    Results  Consistent with previous results, transepidermal  UVR  exerted skin cytotoxicity and epidermal damage. Treatment with high and/or low  UVA + UVB  doses also induced oxidative  DNA  damage and cytotoxicity in human  HF s. In addition, it decreased proliferation and promoted apoptosis of  HF  outer root sheath ( ORS ) and hair matrix ( HM ) keratinocytes, stimulated catagen development, differentially regulated the expression of  HF  growth factors, and induced perifollicular mast cell degranulation.  UVR ‐mediated  HF  damage was more severe after irradiation with high  UVR  dose and reached also proximal  HF  compartments. The topical application of 0.1% caffeine did not induce skin or  HF  cytotoxicity and stimulated the expression of  IGF ‐1 in the proximal  HF ORS . However, it promoted keratinocyte apoptosis in selected  HF  compartments. Moreover, caffeine provided protection towards  UVR ‐mediated  HF  cytotoxicity and dystrophy, keratinocyte apoptosis, and tendential up‐regulation of the catagen‐promoting growth factor.    Conclusion  Our study highlights the clinical relevance of our scalp  UV  irradiation  ex vivo  assay and provides the first evidence that transepidermal  UV  radiation negatively affects important human  HF  functions. This suggests that it is a sensible prophylactic strategy to integrate agents such as caffeine that can act as  HF  photoprotectants into sun‐protective cosmeceutical and nutraceutical formulations.

Transepidermal UV radiation of scalp skin ex vivo induces hair follicle damage that is alleviated by the topical treatment with caffeine