Aging of the Liver: Proteolysis of Oxidatively Modified Glutamine Synthetase

During aging cells accumulate altered forms of proteins, notably oxidatively modified proteins. The multicatalytic protease selectively degrades oxidized proteins, suggesting that the age-related accumulation of oxidized proteins might be a consequence of decreased activity of this protease, The protease activity of liver homogenates was assayed with an improved fluorimetric method, using oxidatively modified glutamine synthetase as substrate, Application of this assay to extracts from liver of Fischer 344 rats from both Japan and the United States demonstrated a marked preference for the oxidized substrate, as expected. Extracts from animals ages 8 to 26 months maintain both total proteolytic activity and the ability to distinguish between native and oxidized substrates. Oxidatively modified hepatocyte extracts were also employed as substrate, and older animals again maintained proteolytic activity. The multicatalytic protease was purified from liver of young and old rats, and the specific activity of the preparations were comparable when assayed with oxidatively modified glutamine synthetase. We conclude that the intrinsic neutral or alkaline proteolytic activity of rat liver is maintained during aging,