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

Abstract

The 2′,5′-oligoadenylate (2–5A) system is involved in the defense of mammalian cells against virus infection. In a previous study [25], we demonstrated that the activities of the enzymes which synthesize and degrade 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 aging and development in different tissues of rat. The age-dependent decrease in 2–5OAS activity and increase in 2–5A nuclease activity results in a decrease in the cellular 2–5A content, suggesting that the efficiency 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 brain using a cDNA which was recently cloned from rat hippocampus. We found that the decrease in 2–5OAS activity is accompanied by a decrease in the level of 2–5OAS mRNA; in old animals (32–33 months old), the amount of 2–5OAS mRNA was reduced to 20–30% compared to young adult (2–3 months old) (100%) and middle-aged adult animals (12 months old) (110–120%). In addition, Western-blotting experiments revealed that the amount of class I 2–5OAS capable of binding to its activator, poly(I)·poly(C), is also diminished in the livers and brains of old rats compared to those of young adult and middle-aged adult animals.