Glucocorticoids and DHEA: Do They Have a Role in Immunosenescence?

This chapter summarizes recent work suggesting that human immunosenescence may be closely related to both psychological distress and stress hormones. The age-related immunological changes are also similarly found during chronic stress or glucocorticoid exposure. It follows that endogenous glucocorticoids (cortisol) could be associated to immunosenescence. When compared with young subjects, healthy elders are emotionally distressed in parallel to increased cortisol/ dehydroepiandrosterone (DHEA) ratio. Furthermore, chronic stressed elderly subjects may be particularly at risk of stress-related pathology because of further alterations in glucocorticoid-immune signaling. Although DHEA and its metabolites have been described with immune-enhancing properties, their potential use as hormonal boosters of immunity should be interpreted with caution. The psychoneuroendocrine hypothesis of immunosenescence is presented in which the agerelated increase in the cortisol/DHEA ratio is major determinant of immunological changes observed during aging. We finally discuss that strictly healthy elders are largely protected from chronic stress exposure and show normal cortisol levels and T-lymphocyte function. This information adds a new key dimension on the biology of aging and stress.