Introduction

All organisms are exposed to stimuli construed as stressors and all organisms mount a characteristic physiologic response to stress to maintain homeostasis (Herman et al., 1996). Many physical illnesses can be linked to life stress, particularly in aged individuals (McEwen & Stellar, 1993; Clauw & Chrousos, 1997; Katz, 1996). Impairments in the physiological responses to stress have particularly been associated with immune, endocrine, neurological, and psychiatric disorders. Examples of neuropsychiatric disorders, which are associated with dysregulation of the stress response, include depression, post-traumatic stress disorder, and neurodegenerative disorders (Kathol et al., 1989; Charney et al., 1993; McEwen, 1992, Landfield & Eldridge, 1991; Sapolsky et al., 1986; Landfield et al., 1992).

Activation of physiologic stress responses involve the sympathetic nervous system and the hypothalamic–pituitary–adrenal (HPA) axis. The HPA axis is the best characterized component of the physiologic stress response. In aging, this stress component undergoes significant changes. As mentioned, changes are associated with neurologic and psychiatric disorders in late life, and it has been hypothesized that these changes are related to the pathogenesis of some of these disorders. The purpose of this chapter is to discuss the alterations in the HPA axis which occur with normal aging and also to relate these changes within the context of disorders of aging. We will initially discuss the physiology of the HPA axis. This discussion will be followed by a discussion of animal and human studies which have examined the HPA axis in normal aging and disease states in late life.