The effects of extracellular matrix degradation mediated by chronic inflammation in aged skin on the structure and function of eccrine sweat glands.

Abstract

Eccrine sweat glands (ESGs) are critical organs for human thermoregulation, yet their function progressively declines with aging. This study aims to investigate the underlying mechanisms responsible for the age-related impairment of ESG function. Through comparative analysis between skin tissues from young and aged mice/human, we observed structural loosening of aged ESG and a significant reduction in the expression of extracellular matrix (ECM) components-type I and type II collagen. Further investigation revealed a significant upregulation of the inflammatory cytokine interleukin (IL)-1β and matrix metalloproteinases and proteases (MMP)-1 in aged tissues, which can modulate the collagen degradation, suggesting that ECM degradation may be regulated by an inflammatory microenvironment. To validate this hypothesis, we established a model of chronic inflammation by intradermally injecting IL-1β into the footpads of mice. The results demonstrated suppressed ESG function, structural loosening of ESG tissues, and a marked reduction of type I and type II collagen surrounding the ESGs. In summary, this study reveals that type I and type II collagen are distributed around ESGs, providing structural and functional support. The activation of the IL-1β-MMP-1 inflammatory pathway in aging may contribute to ESG dysfunction and structural disruption by degrading the collagen around ESGs.