Impaired Angiogenesis and Th1/Th17 Polarization: A Possible Explanation for the Decreased Incidence of Rosacea in the Aged.

Background: Rosacea is a common inflammatory skin disorder characterized by frequent facial flushing, erythema, telangiectasia, and papules, with a higher incidence observed in individuals aged 30-50 years and a tendency to decrease in the elderly. This age-related decline in incidence drew our attention to further explore the relationship between rosacea pathogenesis and aging.

Methods: We analyzed the incidence of rosacea across 8340 individuals without systemic diseases. The effects of LL37-induced rosacea-like erythema and inflammation were evaluated in both young and aged mice. Immunofluorescence analysis was performed to assess microvessel density, whereas the expression levels of angiogenesis-related factors, including matrix metalloproteinases (MMPs) and vascular endothelial growth factor α (VEGFα), were quantified. Additionally, immune responses were assessed at both the cellular and systemic levels.

Results: Aged mice displayed milder LL37-induced rosacea-like erythema and inflammation compared to their young counterparts. Immunofluorescence analysis revealed a decrease in microvessel density in rosacea models of the aged group. The expression of angiogenesis-related factors, including MMPs and VEGFα, was decreased in aged mice compared to young mice, indicating a reduced responsiveness to LL37 stimulation. Furthermore, we found that suppressed Th1- and Th17-polarized immune responses, one of the major pathogenic mechanisms of rosacea, were reduced in aged mice in response to LL37 stimulation at both cellular and systemic levels.

Conclusion: The findings suggest that impaired angiogenesis and attenuated Th1/Th17 immune responses underlie the age-related decline in rosacea incidence.