Stress responses and innate immunity: aging as a contributory factor

Summary Evolutionary pressure has selected individuals with traits that allow them to survive to reproduction, without consideration of the consequences for the post‐child rearing years and old age. In the 21st century, society is populated increasingly by the elderly and with the falling birth rate and improved health care this trend is set to continue for the foreseeable future. To minimize the potential burden on health services one would hope that ‘growing old gracefully’ should also mean ‘growing old healthily’. However, for too many the aging process is accompanied by increasing physical and mental frailty producing an elevated risk of physical and psychological stress in old age. Stress is a potent modulator of immune function, which in youth can be compensated for by the presence of an optimal immune response. In the elderly the immune response is blunted as a result of the decline in several components of the immune system (immune senescence) and a shifting to a chronic pro‐inflammatory status (the so‐called ‘inflamm‐aging’ effect). We discuss here what is known of the effects of both stress and aging upon the innate immune system, focusing in particular upon the age‐related alterations in the hypopituitary–adrenal axis. We propose a double hit model for age and stress in which the age‐related increase in the cortisol/sulphated dehydroepiandrosterone ratio synergizes with elevated cortisol during stress to reduce immunity in the elderly significantly.