Researchers here show that declining cortisol levels cause macrophage cells of the innate immune system to become more inflammatory with age. This contributes to the state of chronic inflammation in older individuals that accelerates the onset and progression of age-related disease. The aging immune system becomes overactive (inflammaging) and less capable (immunosenescence), and its chronic inflammation acts to disrupt tissue maintenance and cell behavior in numerous harmful ways. Loss of cortisol is only a proximate cause of chronic inflammation, however, and the present research says little of how this relates to deeper causes of aging. Nonetheless, it is one of many lines of research that indicate the importance of inflammation to the aging process.

A persistent state of inflammation can cause serious damage to our bodies. One consequence is that chronic inflammatory diseases, such as atherosclerosis or arthritis, are far more prevalent in older patients. What was uncertain up until now was what actually caused these inflammatory responses to flare up. Researchers have now provided some important insight: the inflammatory process is linked to the fact that the amount of cortisol generated in the body decreases as we get older.

Cortisol and its inactive form cortisone, commonly referred to as stress hormones, are released by the adrenal gland. The hormone cortisol acts as a biochemical signalling molecule and is involved in numerous metabolic processes in the body. Cortisol deficiency in the body leads to an inflammatory response. “The serum level of cortisol in the body is lower in the elderly. Moreover, macrophages, an important type of immune cells, can convert inactive cortisone to active cortisol, but this ability declines with increasing age. What we observe is what we could call “macroph-ageing” – the age-induced disruption of macrophage functions.”

Macrophages are important cells within the immune system that use signalling molecules to control other immune cells. They play a critical role in determining the extent of our body’s inflammatory response. However, macrophage function becomes impaired with increasing age. This can lead to an increase in the quantities of pro-inflammatory signalling molecules, which in turn drives the activity of other inflammatory cells of the body’s immune system.

Researchers found that one particular protein is implicated in the malfunctioning of macrophages in the elderly. The protein is known as GILZ and its levels are regulated in part by cortisol. A lower cortisol level causes macrophages to produce less GILZ, which in turn means that the macrophages simply continue to release inflammatory signalling molecules. The team found that GILZ levels are indeed lower in older subjects. To find out whether that in itself was enough to cause an inflammatory response, researchers genetically deactivated the GILZ protein. The data confirmed that the macrophages were activated and there was a resulting increase in chronic inflammatory processes.