Longevity Briefs: How Do The Adrenal Glands Change With Age?

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

There is no organ or tissue in the body that does not show some sign of deterioration in old age. However, when it comes to ageing, the adrenal cortex (the outer layer of the adrenal gland, which sits above each kidney) is less well studied than many other tissues. The adrenal cortex is divided into layers, with each one producing vital hormones. With age, the function of the adrenal cortex declines by way of a phenomenon called adrenal cortex senescence, leading to a reduction in the production of hormones like DHEA and DHEAS. These hormones are linked to mood, cognitive function, metabolism, and bone health. Conversely, the production of the ‘stress hormone’ cortisol tends to increase with age.

Layers of the adrenal cortex and their functions. RAAS (renin-angiotensin-aldosterone system, responsible for regulating water and salt re-absorption in the kidneys), APCCs (aldosterone-producing cell clusters).
*Adrenal cortex senescence: an ageing-related pathology?*

Disruptions in these hormones are associated with declining cognitive function, mood disturbances and osteoporosis (loss of bone density) with age, but does adrenal cortex senescence cause these age-related problems, or is this merely correlation? That question isn’t so easy to answer. In this paper, researchers review what we know so far about the adrenal cortex’s potential contribution to the ageing process.

The discovery:

Researchers reviewed existing studies concerning adrenal gland ageing. Here is a summary of their key findings:

Reduced DHEA/DHEAS: Studies show that circulating DHEA and DHEAS drops with increasing age, potentially due to a smaller zona reticularis (the layer producing these hormones) and changes in gene expression within this layer. However, clinical trials investigating DHEA supplementation in humans produced inconclusive results, possibly due to small sample sizes, short durations and the difficulties of measuring subjective improvements like mood.
Increased Cortisol: Cortisol levels increase with age, potentially due to reduced ability to sense circulating cortisol and the influence of age-related inflammation. High cortisol levels over an extended period are known to shrink neurons, and high levels correlate with cognitive impairment, type II diabetes and cardiovascular disease in older people. However, a causal relationship has not yet been established.
Aldosterone Secretion: Aldosterone is a hormone that regulates blood pressure and salt content, but how its secretion changes in old age is disputed. Some evidence suggests it declines, while other evidence suggests that it is secreted in an unregulated manner.

The implications:

There is evidence (and most importantly, human evidence) to suggest that adrenal cortical function declines with age, leading to hormonal disruptions that are associated with many age-related diseases. This means that there’s a potential opportunity to prevent or treat some of these conditions by targeting the adrenal cortex. Before that becomes a possibility, we’re going to need a lot more research to understand how the adrenal cortex ages, and how exactly disruptions in different hormones contribute to different aspects of the ageing process.

In the meantime, lifestyle factors known to support overall health and modulate ageing, such as maintaining a healthy weight and engaging in regular exercise, are likely to benefit adrenal function. The study’s findings concerning elevated cortisol and cognitive function also support the value of managing stress, irrespective of adrenal function.