Changes with age in peritoneal macrophage functions. Implication of leukocytes in the oxidative stress of senescence

The age-related deterioration of the immune cells contributes to the increased morbidity and mortality of the aged populations. Since ageing is the result of oxidative stress and macrophages are an important source of oxidation, which is produced in order to carry out many of their functions, the changes with age of several macrophage functions as well as of oxidative stress parameters (oxidants, inflammatory mediators and antioxidants) of peritoneal leukocytes have been investigated using young 14 months), adult (7 months), mature (12 months) and old (20 months) female ICR (CD-1) mice. With age the macrophage functions suffer deterioration. Thus, chemotaxis, phagocytosis and intracellular superoxide anion production decrease in old animals. Moreover, the levels of antioxidant defenses, such as superoxide dismutase activity, decrease with ageing. However, the adherence capacity and the release of oxidant and inflammatory mediators, such as extracellular superoxide anion, TNF-alpha and PGE(2), as well as oxidized glutathione/reduced glutathione ratio, increase with age. These results show that these cells suffer oxidative stress with ageing, which results in an increase of the oxidative damage to nuclear DNA. These changes in peritoneal immune cells could contribute to the chronic oxidative stress state linked to senescence.