Post D J, Carter K C, Papaconstantinou J
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
Ann N Y Acad Sci. 1991;621:66-77.
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.
真核生物拥有与它们对损伤、炎症和污染物的反应相关的天然防御过程。其中之一，急性期（AP）宿主反应，其特征是由细菌感染、炎症或组织损伤释放的因子触发的一系列肝脏生理反应，并且被认为是细胞和组织免受进一步损伤和伤害的机制。已知对这些生理损伤的反应能力会受到衰老的影响。我们提出AP反应代表了一系列可能受衰老影响的内在过程和相互作用。此外，我们提出这可能是由于急性期反应的逐渐失效。在这项研究中，我们研究衰老与正负急性期反应物表达之间的关系，即其水平会因全身损伤和感染而升高或降低的急性期血清蛋白。在2、7、12和24月龄的正常和炎症诱导小鼠中测量了正急性期反应物α1-酸性糖蛋白（AGP）、α1-抗胰蛋白酶（AT）以及负急性期反应物白蛋白的mRNA水平。随着年龄增长，AT和白蛋白mRNA的组成水平显著下降。此外，衰老降低了AGP和白蛋白基因对炎症的反应能力。我们的研究表明，衰老可能影响这些基因的转录、mRNA的加工或mRNA水平的稳定性。
