Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged Skin

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.

The link between cutaneous inflammation and cognitive impairment

“…[83][84][85][86] Moreover, expression levels of 11bhydroxysteroid dehydrogenase type 1 are increased in the epidermis of aged skin compared to that of the young skin. 87 The increased 11b-hydroxysteroid dehydrogenase type 1 does not only cause epidermal permeability dysfunction 87 but also increases cytokine production in keratinocytes in response to stimuli. 88 In addition, stratum corneum hydration also regulates cutaneous inflammation.…”

“…Conversely, improvement in epidermal permeability barrier lowers expression levels of pro‐inflammatory cytokines, such as IL‐1α and TNF‐α 83–86 . Moreover, expression levels of 11β‐hydroxysteroid dehydrogenase type 1 are increased in the epidermis of aged skin compared to that of the young skin 87 . The increased 11β‐hydroxysteroid dehydrogenase type 1 does not only cause epidermal permeability dysfunction 87 but also increases cytokine production in keratinocytes in response to stimuli 88 .…”

Synopsis of Barrier Function of Skin and Oral Mucosa—Volume 1

“…Several articles dealt with skin problems relating to aging. 11β-hydroxysteroid dehydrogenase type 1 was shown to be at higher levels in human stratum corneum and oral epithelium compared to younger subjects [12]. The resulting increase in cortisol could cause deterioration of the skin barrier function.…”

Treating Hypopituitarism in the Over 65s: Review of Clinical Studies

“…59 Additionally, the expression of 11beta-HSD1 in several tissues (skin, brain, muscle) is increased both in aging rodents and humans. [60][61][62] Based on the above-mentioned considerations, it is reasonable to reason that older patients need lower glucocorticoid replacement doses than young patients. However, no specific recommendations have been provided for this group of patients by guidelines.…”