Age-related changes of the hypothalamic-pituitary-adrenal axis: pathophysiological correlates

The aim of this review was to examine the evidence for age-related changes of the hypothalamic-pituitary-adrenal (HPA) axis in both physiological and pathological aging, on the basis of the many data in the literature, as wel l as of our personal findings. A statistically significant circadian rhythmicity of serum cortisol was mai ntained in elderly subjects, even if with a reduced amplitude of the 24 h f luctuations and a trend to an increase of the serum levels in the evening a nd at night-time, in comparison with young controls. Furthermore. an age-re lated impairment of HPA sensitivity to steroid feedback was present in elde rly people, The occurrence of senile dementia amplified the changes already present in physiological aging. While the cortisol secretion was generally well mainta ined in aging, the adrenal production of dehydroepiandrosterone and of its sulfate (DHEAS) exhibited an age-related decline. Therefore, the cortisol/D HEAS molar ratio was significantly higher in elderly subjects and even more in demented ones, than in young controls. Due to the opposite effects of cortisol and DHEAS on the brain and particul arly on the hippocampal region, the imbalance between glucocorticoids and a ndrogens occurring in physiological and even more in pathological aging, ma y have adverse effects on the function of this region, whose key role in le arning and memory is well known.