Effects of aging and stress on hippocampal structure and function

Abstract Aging is often simply defined as the decline in various body systems and functions (eg, endocrine, cognitive, motor, etc) that occur with the passage of time, although the degree of deterioration can vary greatly across individuals. Increases in average life span have brought a greater focus on brain aging. There is an emphasis on understanding how aging contributes to a decline in brain functions (eg, cognition) because such a decline adversely affects the quality of life. The hippocampus is a key brain structure for cognition and the feedback control of the stress response. Herein we describe how the hippocampus changes with age and we examine the idea that age-related changes in the secretory patterns of the hypothalamic-pituitary adrenal (HPA) axis can contribute to hippocampal aging. We also examine the proposal that cumulative stress, perhaps due to compromised HPA axis function, can contribute to hippocampal aging by subjecting it to 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, and plastic, electrophysiological, or neurochemical properties of neurons or glia. Dysfunction of the HPA axis sometimes occurs with aging, and while excessive glucocorticoids can disrupt cognition as well as hippocampal neuronal integrity, these are not an inevitable consequence of aging. The general preservation of cells and the plastic potential of the hippocampus provide a focus for the development of pharmacological, nutritional, or life-style strategies to combat age-related declines.