Glucocorticoid metabolism and function in ageing skin

Tiganescu, Ana (2012). Glucocorticoid metabolism and function in ageing skin. University of Birmingham. Ph.D.

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Abstract

Increased demographic proportions of elderly individuals are driving research into healthy lifespan. Excessive circulating glucocorticoids (GC) often cause hypertension, osteoporosis, central obesity, muscle weakness, skin thinning and poor wound healing (e.g. Cushing’s Syndrome) – conditions common in ageing.
The GC-activating enzyme 11-beta hydroxysteroid dehydrogenase type 1 (11β-HSD1) displays increased activity in bone cells from older vs. younger donors. Here, we report similar findings in the organ most noticeably affected by ageing – skin. 11β-HSD1 activity was increased in skin from older vs. younger donors with increased expression in dermal fibroblasts from the former. GC induced activity exclusively in cells from older individuals, further increasing dermal GC-generating ability. We demonstrate 11β-HSD1-specific regulation of novel GC target genes that may be dysregulated during ageing which correlate with enzyme activity. Finally, studies characterizing the skin phenotype of aged 11β-HSD1-null mice reveal exciting morphological similarities to skin from young mice.
GC therapy is common for elderly skin disorders (e.g. xerosis, pemphigoid and psoriasis). However, elderly patients are more susceptible to side-effects including thinning, bruising, tearing and infection. We identify 11β-HSD1 as a novel therapeutic target to minimize GC-induced side-effects in the elderly, improve the phenotype of ageing skin and limit associated pathologies.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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