263 Effect of environmental stress combined with “daily life stress” on skin aging

Abstract

The consequences of stress on the human organism are well established and can be characterized. Daily life stress mainly impacts the hypothalamic-pituitary-adrenal (HPA) axis, which regulates glucocorticoid (GC) secretion by the adrenal gland cortex through adrenocorticotropic hormone (ACTH) released by the hypophysis, under the control of hypothalamic corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP). Cortisol (the hormone of stress) and dehydroepiandrosterone (DHEA) represent the main GCs in humans and act on specific receptors present in most peripheral tissues, including the skin. Chronic exposure to stressful events leads to excessive stimulation of the HPA axis and hypercortisolemia, which plays a pathophysiological role in the development of a variety of stress-related diseases. In the skin, elevated cortisol induces changes that are similar to those involved in the natural aging process. Locally, 11β-hydroxysteroid dehydrogenases (11β-HSD1 and 2) play a major role in regulating the impact of cortisol in the skin tissue. With the goal to study the impact of elevated cortisol in skin tissue, and more particularly on cellular senescence and repair capacity, 3D engineered skin models were developed. The consequences of the exposure of external stress such as UV on stressed reconstructed skin induced by various concentrations of cortisol was also investigated. The new skin reconstructed models obtained in this study represent a promising tool for monitoring the impact of elevated concentrations of cortisol on the skin and to identify biofunctional ingredients or chemical substances with modulatory potential in vitro.