Role of Stress and Hormones of the Hypothalamic-Pituitary-Adrenal (HPA) Axis in Aging

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis is one of the most important allostatic systems that allow a person to respond and adapt against diverse stresses by upregulating the glucocorticoids and adrenal androgens. However, its inhibition is equally important to prevent against deleterious effect of its overex-posure to neuroendocrine and inflammatory stresses. This chapter aims to examine the effect of stress and aging on the dysregulation of the HPA axis. Chronic stress and aging are phenomenons that have complex interaction at the level of HPA axis; while chronic stress promotes aging, consequently aging leads to dys-regulated stress management. The effects of the terminal regulators of the HPA axis like glucocorticosteroids (GCs; cortisol) and adrenal androgens (DHEA and its sulfate; DHEAS) are drastically opposite; while cortisol promotes neuronal cell death and degeneration, DHEAS plays protective role against neuronal impairment. With age there is a marked increase in the nocturnal as well as 24 h circulating cortisol secretion accompanied by clear flattening of the diurnal rhythm of cortisol secretion evident from both animal and human studies. Also, there is a clear dysregulation of the negative feedback inhibition of the GC secretion in chronic stress and aging. Besides, the androgenic steroids like DHEA/ DHEAS secreted in response to ACTH also undergo marked depreciation in elderly subjects. Consequently, there is a marked increase in the cortisol/DHEAS molar ratio with physiological and pathological aging. Hence, the dysregulation in these two classes of steroids with aging and chronic stress and their manifestations are examined in detail in this chapter.