Changes in hepatic DNA binding proteins as a function of age in rats

The process of aging is accompanied by many changes in gene expression, occurring in virtually all organs of the affected individual. Here we report on the relative changes in DNA binding activity of a panel of 15 different transcription factors in the liver of adult (15-month-old) and old (25-month-old) Sprague-Dawley rats. When expressed as a function of nuclear protein concentration, a great majority of the transcription factors analyzed do not show significant differences in DNA binding activities as a function of age, except activator protein 1 (AP-1) and nuclear factor-kappa B, both of which show increased activities in the older animals, and hepatocyte nuclear factor-3, which undergoes a switch from predominantly alpha and beta subspecies in the adults, to predominantly gamma subspecies in the old animals. Further examination of some of the members of the AP-1 complex using Western blot analysis indicates that the increase in binding activity of this particular complex might be due to an increase in the relative mass of Jun B, presumably resulting in a switch from predominantly c-Fos/Jun D in the young to c-Fos/Jun B complexes in the old animals. Nuclear extracts prepared from the liver of old animals yield less proteins per mass of DNA than similar extracts prepared from younger animals. Accordingly, if the data are analyzed as a function of genomic DNA, our results indicate that aging results in a consistent, but generally not statistically significant decrease in most transcription factor DNA binding activities, with AP-1, nuclear factor-kappa B, and transcription factor II D being the exception to this decline.