Researchers here review what is known of the structural and functional aging of the adrenal gland, and conclude that this is an understudied area. While it is fairly clear that changes in signaling generated by the adrenal gland can be hypothesized to be harmful over the long term, based on what is known of the roles of DHEA, cortisol, and so forth, it remains to be demonstrated conclusively that adrenal gland aging directly contributes to the onset and progression of the age-related conditions it correlates with.
Our hypothesis is that structural and functional changes of the adrenal cortex develop and progress with increasing age, resulting in reduced secretion of DHEA/DHEAS and increased secretion of cortisol. It is important to obtain further evidence to better characterise the degenerative changes of the adrenal cortex, and to elucidate the clinical consequences of this. Adrenal cortex senescence is an emerging entity which appears to fulfil the criteria for an ageing-related pathology.
Functional changes are observed with increasing chronological age, in particular there is reduced secretion of DHEA and DHEAS, and there is increased output of cortisol. Such changes are associated with a range of adverse clinical outcomes, including an increased risk of premature mortality, systemic lupus erythematosus (SLE), dementia, breast cancer, rheumatoid arthritis, schizophrenia, bipolar affective disorder, depression, Alzheimer's disease, diabetes, and low bone mineral density. These findings have been reported in studies carried out in humans.
However, further evidence is required before adrenal cortex senescence can be definitively regarded as an age-related pathology. Whilst numerous diseases are associated with low serum DHEA/DHEAS, this may just be an association, or a consequence of the disease process. It remains to be determined whether reduced secretion of DHEA/DHEAS has any pathological outcomes. Similarly, it is important to advance the understanding of whether the increased cortisol output observed with increasing age mediates any adverse clinical effects, its underlying pathophysiology, and to better characterise the ageing-related changes in aldosterone secretion. Furthermore, much of the research considering the structural and morphological changes of the ageing adrenal gland has been carried out in animal models, and evidence from human studies is relatively scarce.
Link: https://doi.org/10.1007/s40618-025-02566-9
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