Nutrition and age-associated inflammation: implications for disease prevention

Accumulating evidence suggests that aging is associated with dysregulated immune and inflammatory responses. Investigation into the cellular and molecular mechanisms underlying this phenomenon suggests that an up-regulated cyclooxygenase (COX)-2 expression, and resulting increase in production of prostaglandin E(2) (PGE(2)), is a critical factor. Macrophages from old mice have significantly higher levels of PGE(2) production compared with those from young mice, a result of increased COX-2 expression and protein levels leading to increased COX enzyme activity. Furthermore, studies suggest that the age-associated increase in macrophage PGE(2) production is due to ceramide-induced up-regulation of nuclear factor-kappa B activation. Such processes may also occur in cell types other than macrophages, lending further insight into potential mechanisms of age-related diseases. Moreover, the excess PGE(2) induces harmful effects in other cell types such as T cells and adipocytes through the negative crosstalk between macrophages with other cells, resulting in further increased susceptibility to diseases. Nutrient/dietary medications, such as antioxidants and certain lipids have suggested a promising route to reduce the age-related increase in COX activity and PGE(2) production that is associated with several disease states.