The effect of aging on constitutive mRNA levels and lipopolysaccharide inducibility of acute phase genes.

Eukaryotic organisms possess natural defense processes associated with their response to injury, inflammation and pollutants. One of these, the acute phase (AP) host response, is characterized by a series of hepatic physiological reactions triggered by factors released as a result of bacterial infection, inflammation or tissue injury and is believed to be the mechanism by which cells and tissues are protected against further damage and injury. The capacity to respond to these physiological insults is known to be affected by aging. We propose that the AP response represents a series of intrinsic processes and interactions that may be affected by aging. Furthermore, we propose that this may be due to the progressive failure of the acute phase response. In this study we examine the relationship between aging and the expression of both positive and negative acute phase reactants, i.e., acute phase serum proteins whose levels are increased or decreased in response to systemic injury and infection. The mRNA levels of the positive acute phase reactants, alpha 1-acid glycoprotein (AGP), alpha 1-antitrypsin (AT), and the negative acute phase reactant, albumin were measured in both normal and inflammation-induced mice of ages 2, 7, 12, and 24 months. A significant decrease in the constitutive levels of AT and albumin mRNAs occurred as a function of increased age. Furthermore, aging decreased the ability of the AGP and albumin genes to respond to inflammation. Our studies indicate that aging may affect the transcription of these genes, processing of their mRNA or stability of the mRNA levels.