Adrenal Aging and Its Implications on Stress Responsiveness in Humans

Abstract

Normal aging results in subtle changes both in ACTH and cortisol secretion. Most notable is the general increase in mean daily serum cortisol levels in the elderly, without a noteworthy alteration in the normal circadian rhythm pattern. Glucocorticoid excess seen in the elderly population can have serious consequences in both the structural and functional integrity of various key areas in the brain, including the hippocampus, amygdala, prefrontal cortex, with consequent impairment in normal memory, cognitive function, and sleep cycles. The chronically elevated glucocorticoid levels also impinge on the normal stress response in the elderly, leading to an impaired ability to recover from stressful stimuli. In addition to the effects on the brain, glucocorticoid excess is associated with other age-related changes, including loss of muscle mass, hypertension, osteopenia, visceral obesity, and diabetes, among others. In contrast to the increase in glucocorticoid levels, other adrenocortical hormones, particularly serum aldosterone and DHEA (the precursor to androgens and estrogens) show significant decreases in the elderly. The underlying mechanisms for their decrease remain unclear. While the adrenomedullary hormone, norephinephrine, shows an increase in plasma levels, associated with a decrease in clearance, no notable changes observed in plasma epinephrine levels in the elderly. The multiplicity and complexity of the adrenal hormone changes observed throughout the normal aging process, suggests that age-related alterations in cellular growth, differentiation, and senescence specific to the adrenal gland must also be considered.

Activation of Adrenal Steroidogenesis and an Improvement of Mood Balance in Postmenopausal Females after Spa Treatment Based on Physical Activity

“…The latter steroids are the primary ligands for both MR and GR in the CNS [89]. Furthermore, besides the adrenal androgens, the aldosterone secretion and renin activity also decline with age [90], which further support the major role of glucocorticoids during aging.…”

“…As the GR antagonists induce an impairment of memory storage, the MR antagonists inhibit the memory retrieval [89]. The hippocampus (HC) and prefrontal cortex (PFC) primarily inhibit the limbic-HPAA activity, while amygdala activates the stress response [90]. While the MR regulates a tonic effect of glucocorticoids in the brain at basal levels, the activation of the GR blunts further activity of the stress response [89,90].…”

“…However, the very intense stress situations induce a delayed, more pronounced and long-lasting amygdala activity [89]. Whereas the activation of the MR promotes the hippocampal plasticity, GR exerts the opposite effect [90]. The MR principally control the threshold of reactivity of the HPAA during stress, which is generally considered to be a healthy state [89].…”

“…Aging is associated with weakened negative feedback on the cortisol secretion, due to impaired sensitivity of the HPAA [90]. The elevation of cortisol levels is frequently related to a lower cognitive status, anxiety, depression, dementia, and neurodegenerative diseases.…”

Epidermal Mineralocorticoid Receptor Inactivation Affects the Homeostasis of All Skin Layers in Chronologically Aged Mice

“…Skin anomalies associated with prolonged elevated GC levels also found in the elderly population include epidermal thinning and dermal atrophy with increased fragility, tearing and bruising, impaired wound healing, increased dehydration, and increased infection risk (Pérez, 2011;Schäcke et al, 2002). Indeed, GCs are likely responsible for many of these detrimental effects as they can be elevated systemically in the elderly owing to alterations in circadian rhythm and impaired sensitivity of the hypothalamic-pituitary-adrenal axis (Yiallouris et al, 2019). Furthermore, even before serum cortisol levels are detected as increased in aging individuals, active GCs are predicted to be elevated in aging skin as a result of increased local production (Tiganescu et al, 2018).…”