Aging and Adrenocortical Factors

Abstract

Some of the most interesting factors associated with aging is the significant interindividual variability in mental and physical changes. Identifying factors that can explain this heterogeneity is thus of great interest to many research groups around the world. One factor that is often investigated for its role in the aging process is stress, and the effect it has on the body. The hypothalamic-pituitary-adrenal (HPA) axis is the major neuroendocrine system that regulates the body’s response to stress, by changing its activity, resulting in a release of a cascade of hormones, with cortisol being the final product in humans. A number of theories propose that high amounts of stress lead to a change of regulation of this system over time, which can then become a risk factor for psychological and physical disease in older age. These theories include the general adaptation syndrome, the allostatic load model, and the glucocorticoid cascade hypothesis. They argue that with high amounts of stress over time individuals become more prone to disease, especially with advanced age. There is some evidence for mechanisms relating to the HPA axis and stress-related disease in aging in accordance with these models; however, findings from especially more recent studies question the strength of these effects. It appears that other factors, especially events early in life can have a lifelong, programming effect on the regulation of the HPA axis, sometimes stronger than age-related changes. Newer theories such as life history theory consider these effects, and can complement previous models to better explain the available data. Currently, studies are underway to determine how well these theories can be combined to explain age-related disease.