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The HPA axis also undergoes age-related changes including alterations in the sensitivity and responsiveness of the hypothalamus and pituitary gland to negative feedback by cortisol, changes in the levels and circadian rhythm of circulating cortisol, changes in the expression and function of CRH and glucocorticoid receptors in the hypothalamus, hippocampus, and prefrontal cortex, changes in the activity and connectivity of brain regions involved in stress regulation, including the amygdala, hippocampus, and prefrontal cortex, and changes in the microbiota, which can impact HPA axis function and contribute to inflammation and oxidative stress (110)
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