Age-dependent decrease in the activity of protein-synthesis initiation factors in rat brain.

The age-dependent reduction of brain protein synthesis was examined at the initiation step of translation in the rat. Activity of brain initiation factor 2, as well as that of other eukaryotic initiation factors that contribute to the binding of initiator aminoacyl-tRNA to ribosomes, was found to decrease with age and to decline parallel to the decrease in total protein synthesis and brain elongation factor 1 activity. Change in the activity of initiation factors was demonstrated by the results of two different assays which compared favorably with each other. Decreased activity of preparations of initiation factors derived from older animals was observed in: (1) saturating conditions; (2) mixtures of preparations from different ages; and (3) both major cell fractions, i.e. cell sap and microsomes.