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TU Dresden

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In the past we have investigated the connection between glucocorticoids and age-related disorders such as osteoporosis and type-2 diabetes. Glucocorticoids are stress hormones produced by the adrenal gland affecting most cells and tissues in the body. At high concentrations glucocorticoids have powerful immunosuppressive properties. Therefore, they are commonly used in clinical medicine, for instance to treat autoimmune disorders.

However, at their lower, more physiological concentration glucocorticoids are important for the adequate maintenance fuel metabolism, immune function, bone and connective tissue homeostasis as well as growth, development and regeneration. Frequently, chronic disease are linked to the deregulation of either local or systemic glucocorticoid signalling. Glucocorticoids have for instance been implicated in the development of a wide range of diseases such as depression, metabolic syndrome and osteoporosis.

Given the important role of glucocorticoids in the stress response, we were interested in the effects, which chronic stress exposure exerts on bone tissue. Here we were able to show that chronic stress causes a profound imbalance in the skeletal renewal process. The skeleton is constantly being broken down and regenerated. In fact, in humans the skeleton is completely replaced every 10 years (as long as we are still young). In rodents, this process runs even faster. Excessive stress exposure introduced an imbalance in this renewal process via glucocorticoid signalling in bone-forming cells. Ultimately, the stress-induced rise in glucocorticoid levels lead to a loss of bone mass.

In our most recent project we investigated the role of glucocorticoids in the context of ageing and metabolic decline. We were able to show that glucocorticoid signalling in the skeleton can exert an important effect on whole-body energy homeostasis during ageing. This effect was particularly powerful in the functional decline of adipose tissue during ageing. Through the genetic manipulation of glucocorticoid signalling in bone-forming osteoblasts adipose tissue remained functionally active at old age, thus preventing the onset of obesity and insulin resistance. These results opened up the exciting possibility that glucocorticoids may mediate some aspects of the mammalian ageing process.