Effects of aging on the various steps of protein synthesis: fragmentation of elongation factor 2.

The possible mechanism responsible for the in vivo protein synthesis decline during aging was studied. In order to determine the effect of aging on the various steps of protein synthesis, we determined the ribosomal state of aggregation and the time of assembly and release of polypeptide chains in the process of protein synthesis in rat liver. The results suggest that elongation is the most sensitive step to aging. A molecular study of the Elongation Factor 2 (EF-2), the main protein involved in the elongation step, shows that this protein has a higher content of carbonyl groups and is less active in old rats. In addition, the molecular mass analysis of EF-2 shows that this protein becomes fragmented in old rats. A similar pattern of fragmentation is found in 3-month-old rats suffering oxidative stress, in that the decline in protein synthesis is similar to that found in old rats. These data suggest that: i) oxidative stress seems to be involved in the modifications of EF-2 observed during aging, and ii) the observed modifications (oxidation and fragmentation) of EF-2 could account for the decline in protein synthesis in old animals.