Age-related functional alteration of mouse liver ribosomes

The in vitro functional capacity of the mouse liver protein synthesis machinery was studied as a function of age. Polysomes from young (one-three months old) and old (18–24 months old) C57BL/6J mice were incubated under standard conditions in a ribosome-free reticulocyte lysate containing [³H]-leucine. The incorporation of radioactivity into hot TCA-insoluble material was measured as a function of time and kinetic curves were compared. A drastic age-related decrease in the initial rate of leucine incorporation was observed when the total ribosomal fraction (containing the whole range of ribosomal aggregates including subunits and single ribosomes) was assayed. When “heavy polysomes” (fractions from which subunits and single ribosomes had been excluded) were compared, the same difference was observed. This latter result indicated that the observed alteration may be attributed to actively translating ribosomes. Results from experiments using inhibitors of initiation suggest that the observed age-related alteration can be attributed to a reduced capacity of ribosomes from older animals to sustain reinitiation.