IMPAIRMENT OF INTRACELLULAR ANTIVIRAL DEFENSE WITH AGE - AGE-DEPENDENT CHANGES IN EXPRESSION OF INTERFERON-INDUCED AND DOUBLE-STRANDED RNA-ACTIVATED 2-5A SYNTHETASE IN RAT

The 2',5'-oligoadenylate (2-5A) system is involved in the defense of m ammalian cells against virus infection. In a previous study [25], we d emonstrated that the activities of the enzymes which synthesize and de grade 2-5A [2-5A synthetase (2-5OAS) and 2',3'-exoribonuclease] and of the enzyme that is activated by 2-5A (ribonuclease L) change during a ging and development in different tissues of rat. The age-dependent de crease in 2-50AS activity and increase in 2-5A nuclease activity resul ts in a decrease in the cellular 2-5A content, suggesting that the eff iciency of the antiviral 2-5A system is impaired in aged rats. Here we determined the age-dependent changes in the level of mRNA coding for the class I isoenzyme of 2-5OAS (M(r) 40-46 kDa) in rat liver and brai n using a cDNA which was recently cloned from rat hippocampus. We foun d that the decrease in 2-50AS activity is accompanied by a decrease in the level of 2-5OAS mRNA; in old animals (32-33 months old), the amou nt of 2-5OAS mRNA was reduced to 20-30% compared to young adult (2-3 m onths old) (100%) and middle-aged adult animals (12 months old) (110-1 20%). In addition, Western-blotting experiments revealed that the amou nt of class I 2-5OAS capable of binding to its activator, poly(I). pol y(C), is also diminished in the livers and brains of old rats compared to those of young adult and middle-aged adult animals.