Alcohol, aging, and the stress response

R L Spencer, K E Hutchison, R L Spencer, K E Hutchison

Abstract

The body responds to stress through a hormone system called the hypothalamic-pituitary-adrenal (HPA) axis. Stimulation of this system results in the secretion of stress hormones (i.e., glucocorticoids). Chronic excessive glucocorticoid secretion can have adverse health effects, such as Cushing's syndrome. Alcohol intoxication activates the HPA axis and results in elevated glucocorticoid levels. Ironically, elevated levels of these stress hormones may contribute to alcohol's pleasurable effects. With chronic alcohol consumption, however, tolerance may develop to alcohol's HPA axis-activating effects. Chronic alcohol consumption, as well as chronic glucocorticoid exposure, can result in premature and/or exaggerated aging. Furthermore, the aging process affects a person's sensitivity to alcohol and HPA axis function. Thus, a three-way interaction exists among alcohol consumption, HPA axis activity, and the aging process. The aging process may impair the HPA axis' ability to adapt to chronic alcohol exposure. Furthermore, HPA axis activation may contribute to the premature or exaggerated aging associated with chronic alcohol consumption.

Figures

Figure 1
Figure 1
The three-way interaction of alcohol, cortisol secretion, and the aging process. Cortisol secretion is an indicator of the activity of the hypothalamic-pituitary-adrenal (HPA) axis, a hormone system that coordinates the stress response. Alcohol consumption stimulates cortisol secretion (1a). In turn, cortisol facilitates alcohol’s rewarding effects (1b). Chronic alcohol consumption also can lead to premature and/or exaggerated aging (2a). Conversely, the aging process results in increased blood alcohol levels following consumption of the same alcohol dose as well as increased vulnerability to alcohol’s effects, including alcohol’s abuse potential (2b). Finally, chronic cortisol elevation also results in premature and/or exaggerated aging (3a), and the aging process can lead to increased cortisol secretion by impairing the organism’s ability to adapt to stress (3b).
Figure 2
Figure 2
Schematic representation of the hypothalamic-pituitary-adrenal (HPA) axis. In response to stimulatory neural input from other brain regions (e.g., in stressful situations), certain cells in the brain’s hypothalamus secrete corticotropin-releasing hormone (CRH). This hormone stimulates cells in the pituitary gland, which is located below the hypothalamus, to secrete adrenocorticotropic hormone (ACTH) into the bloodstream. ACTH then is transported to the adrenal glands located atop the kidneys, where it activates certain cells to release cortisol, which exerts numerous metabolic effects. The HPA axis is regulated by both direct and indirect negative feedback mechanisms. Thus, cortisol directly inhibits further release of CRH from the hypothalamus and ACTH from the pituitary gland and indirectly lowers CRH secretion by reducing the neural input from other brain regions. NOTE: + = stimulatory effect; –= inhibitory effect.

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