Effect of short-term, low dose aspirin supplementation on the activation of pro-inflammatory NF-κB in aged rats

The basis of our recently proposed “molecular inflammation theory of aging” is that activated inflammatory transcription factors, including versatile NF-κB, occur widespread in the organism during aging. NF-κB plays a key role in pro-inflammatory gene expression, such as cyclooxygenase (COX). Aspirin is one of the most commonly used non-steroidal anti-inflammatory drugs because of its ability to inhibit COX activity. Thus, in the present study, we investigated the effect of short-term, low dose aspirin intake on the modulation of pro-inflammatory NF-κB activation in old rats. To conduct the study, 24-month-old Fischer 344 rats were supplemented with low dose aspirin (0.015%) for 10 days. Biochemical analyses showed suppressed reactive species (RS) and COX-2 activity. The data also showed that NF-κB activation and its associated gene expressions, such as COX-2, iNOS, VCAM-1 and ICAM-1, were all suppressed by the low dose aspirin supplementation through the inhibition of phosphorylation and degradation of IκBα via the NIK/IKK pathway. Our molecular exploration further revealed that aspirin's suppressive action of NF-κB was mediated by its ability to inhibit the nuclear translocation of cytosolic thioredoxin and redox factor-1. These findings showed for the first time that in aged rat short-term low dose dietary aspirin feeding modulates the molecular signal transduction involved in the inflammatory process.