Aging, stress and the hippocampus

Abstract

Functional loss often occurs in many body systems (e.g., endocrine, cognitive, motor) with the passage of years, but there is great individual variation in the degree of compromise shown. The current focus on brain aging will continue because demographic trends indicate that the average lifespan will show a continued increase. There is increasing emphasis on understanding how aging contributes to a decline in brain functions, cognition being a prime example. This is due in part to the fact that dementias and other losses in brain function that sometimes accompany aging cause an obvious decline in the quality of life and these deficits are of more concern as the number of elderly increase. Stress also is a ubiquitous aspect of life and there is now a greater interest in understanding the role of stress and the stress response in brain aging. The key role of the hippocampus and its related brain structures in cognition, as well as in the feedback control of the response to stress, have made this brain area a logical focus of investigation for those interested in the impact of stress on brain aging. Here, we describe how the hippocampus changes with age and we examine the idea that age-related changes in the secretion patterns of the hypothalamic-pituitary adrenal (HPA) axis can contribute to aging of this structure. We also examine the proposal that stress, perhaps due to compromised HPA axis function, can contribute to hippocampal aging through exposure to excessive levels of glucocorticoids. The aging hippocampus does not appear to suffer a generalized loss of cells or synapses, although atrophy of the structure may occur in humans. Thus, age-related cognitive impairments are likely related to other neurobiological alterations that could include changes in the signaling, information encoding, plasticity, electrophysiological or neurochemical properties of neurons or glia. Although excessive levels of glucocorticoids are able to interfere with cognition, as well as hippocampal neuronal integrity, and aging is sometimes accompanied by an increase in these steroids because of inadequate feedback control of the HPA axis, none of these are a foregone consequence of aging. The general preservation of cells and the plastic potential of the hippocampus provide a focus for the development of pharmacological, nutritive or lifestyle strategies to combat age-related declines in the hippocampus as well as other brain areas.