Abstract
Inactive cortisone is converted into active cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Excessive levels of active glucocorticoids could deteriorate skin barrier function; barrier impairment is also observed in aged skin. In this study, we aimed to determine whether permeability barrier impairment in the aged skin could be related to increased 11β-HSD1 expression. Aged humans (n = 10) showed increased cortisol in the stratum corneum (SC) and oral epithelium, compared to young subjects (n = 10). 11β-HSD1 expression (as assessed via immunohistochemical staining) was higher in the aged murine skin. Aged hairless mice (56-week-old, n = 5) manifested greater transepidermal water loss, lower SC hydration, and higher levels of serum inflammatory cytokines than the young mice (8-week-old, n = 5). Aged 11β-HSD1 knockout mice (n = 11), 11β-HSD1 inhibitor (INHI)-treated aged wild type (WT) mice (n = 5) and young WT mice (n = 10) exhibited reduced SC corticosterone level. Corneodesmosome density was low in WT aged mice (n = 5), but high in aged 11β-HSD1 knockout and aged INHI-treated WT mice. Aged mice exhibited lower SC lipid levels; this effect was reversed by INHI treatment. Therefore, upregulation of 11β-HSD1 in the aged skin increases the active-glucocorticoid levels; this suppresses SC lipid biosynthesis, leading to impaired epidermal permeability barrier.
Highlights
Various physiological parameters in aged skin, including structure, wound healing ability, immune function, and metabolism, show changes compared to those in young skin [1,2,3,4,5]
The skin barrier function reportedly deteriorates with an increased surface pH, leading to impaired skin integrity and cohesion and delayed barrier recovery, due to the reduction of epidermal lipid synthesis [6,7,8]
GCfunction producand structure of the aged skin may be due to the increased local GC production, which tion, which is largely mediated by 11β-HSD1 [14,29]
Summary
Various physiological parameters in aged skin, including structure, wound healing ability, immune function, and metabolism, show changes compared to those in young skin [1,2,3,4,5]. The skin barrier function reportedly deteriorates with an increased surface pH, leading to impaired skin integrity and cohesion and delayed barrier recovery, due to the reduction of epidermal lipid synthesis [6,7,8]. These characteristics of the aged skin are similar to the changes caused by excessive endogenous or exogenous glucocorticoid (GC) levels [2]. Physiological changes in the aged skin might be associated with the increase of the active GC level [2,14,15,16]
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