Synergistic effects of Ageing and Stress on Neutrophil function

Although ageing is a complex process, we now know much of what happens with age at the cellular and tissue level. In contrast, our understanding of how the various age-related changes interact to result in frailty and pathology is incomplete. For example ageing is accompanied by a loss of immune function (Immunesenescence), an increase in the level of circulating pro-inflammatory cytokines (Inflammaging), a decline in adrenal androgen production (Adrenopause) whilst concurrently peripheral glucocorticoid activation increases. In this article we propose that these changes in combination increase the susceptibility of older adults to the adverse effects of physical and emotional stress, exacerbating the age-related decline in immune competence and exposing the older individual to increased risk of infections. We have focused upon the effects of stress and ageing on neutrophil function, an element of the immune system that has received less attention from immunogerontologists, despite the primary role of neutrophils in fighting bacterial infections and the major contribution of such infections to age-related morbidity and mortality. We propose that physical and emotional stressors elicit an exaggerated response in older adults that synergises with the age-related loss of neutrophil function, to compromise anti-bacterial mechanisms. Moreover, the molecular basis of this effect may lie with the significant changes in tissue concentrations of cortisol and dehydroepiandrosterone in peripheral target cells including the immune compartment.