Age-related changes in the regulation of autophagic proteolysis in rat isolated hepatocytes

During intervals between meals, autophagy is a major source of nutrients and may remove dam aged organelles and membranes. Age-related changes in the regulation of autophagic proteolysis were studied by monitoring the rate of valine release from liver cells of 2-, 6-. 12-, 18-, and 24-month-old male Sprague-Dawley rats fed ad libitum, and incubated in vitro with added amino acids and 10(-7) M of insulin or glucagon. The maximum rate of proteolysis and its maximum inhibition by amino acids were reached at 6 months and declined thereafter. In contrast. the rate of protein degradation in the presence of high concentrations of amino acids was not affected by aging. The inhibitor effect of insulin was additive to that of amino acids and was not altered significantly by age. The conclusion is that altered regulation of autophagic proteolysis decreases susceptibility of older cells to lysosomal degradation, and it may lead to the accumulation of altered organelles and membranes.