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Hypothalamic-pituitary-adrenal (HPA) axis and aging.
Deepashree Gupta1, John E Morley
1Division of Endocrinology, Saint Louis University, Missouri, St. Louis; Divisions of Endocrinology and Geriatric Medicine, Saint Louis University, Missouri, St. Louis.
Comprehensive Physiology
|November 28, 2014
Summary
Aging is linked to hypothalamic-pituitary-adrenal (HPA) axis dysfunction, affecting cognition and physical health. This review explores HPA axis changes in aging, including altered hormone levels and feedback mechanisms.
Area of Science:
- Endocrinology
- Neuroscience
- Gerontology
Background:
- Human aging is characterized by increased frailty and morbidity.
- Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is implicated in age-related diseases such as depression, cognitive decline, and Alzheimer's disease.
- HPA axis dysfunction may also contribute to sarcopenia and reduced physical performance in older adults.
Purpose of the Study:
- To review the pathophysiology of HPA axis dysfunction in the context of human aging.
- To examine the relationship between HPA axis alterations and age-related cognitive and physical decline.
- To discuss the complex and sometimes conflicting findings regarding HPA axis function in aging.
Main Methods:
- Literature review of studies investigating HPA axis function in aging.
- Analysis of hormonal changes including adrenocorticotropic hormone (ACTH), cortisol, pregnenolone, DHEA, and aldosterone.
- Examination of glucocorticoid (GC) negative feedback mechanisms in the hypothalamus, hippocampus, and prefrontal cortex.
Main Results:
- Aging is associated with increased basal ACTH and cortisol secretion.
- Glucocorticoid negative feedback is impaired at the level of the paraventricular nucleus (PVN), hippocampus (HC), and prefrontal cortex (PFC).
- Diurnal cortisol patterns flatten, and there is a decline in pregnenolone and DHEA with aging. Aldosterone may decrease, but some older individuals are predisposed to hyperaldosteronism.
Conclusions:
- HPA axis dysfunction is a significant factor in aging, contributing to both cognitive and physical impairments.
- Altered hormone secretion and feedback mechanisms characterize the aging HPA axis.
- Further research is needed to resolve controversies and fully understand the HPA axis's role in aging.
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