Aging-Related Changes in Cutaneous Corticotropin-Releasing Hormone System Reflect a Defective Neuroendocrine-Stress Response in Aging

Abstract

Skin, being a mirror of the body, is a major target for aging research. Aging is a complex process that involves the decline of function or dysfunction of many systems. The corticotropin-releasing hormone (CRH) system is involved in skin inflammation. In addition, CRH has a suggested role in age-associated conditions and in animal aging models. However, a consistent logic interaction between the different CRH system components and the aging process has, to our knowledge, never been examined before. The expression of CRH, CRH-binding protein (CRHBP), CRH receptor 1 (CRHR1), and CRH receptor 2 (CRHR2) in healthy skin samples of 42 patients of different ages (18-92 years) was evaluated by immunohistochemistry, and the age-related changes were assessed. Compared with young skin, the aged skin displayed an upregulation of CRH in sebaceous glands and CRHR1 in hair follicles and the epidermis. Moreover, age-associated downregulation of CRHBP in the sebaceous and sweat glands was detected, whereas the CRHR2 showed no age-related changes. Our findings suggest that the age-associated changes in the expression of CRH system components reflect an exaggerated stress response reaction, putting the aged skin continuously in a stress-like situation.