Aging is characterized by a profound reduction in anti-inflammatory lipoxin A4 levels

Ongoing low-grade chronic inflammation represents a pathogenetic background for age-related diseases. In this report, we tested the hypothesis that endogenous anti-inflammatory mechanisms may become less efficient with age, resulting in increased susceptibility to inflammatory disorders. Using previously validated ELISA assays, we evaluated urinary levels of the anti-inflammatory, pro-resolution, arachidonic acid (AA) metabolite, lipoxin (LX)A(4) and of the pro-inflammatory cysteinyl leukotrienes (cysLTs) in volunteers aged from 26 to over 100 years. (i) LXA(4) excretion was decreased in elderly people, resulting in a profound unbalance of the LXA(4)/cysLTs ratio, which may be considered an index of the endogenous anti-inflammatory potential. A significant inverse correlation was denoted between age and the LXA(4)/cysLTs ratio (rho = -0.41, P = 0.0026). We conclude that aging is associated with a switch in arachidonic acid metabolism that prevents formation of key 'stop signals' of the inflammatory reaction. This may contribute to promote the development of disease in elderly. (c) 2005 Elsevier Inc. All rights reserved.