Does the capacity of ribosomes to control translation fidelity change with age?

The stress of increased magnesium concentration and of antibiotic action was used to test for changes in the capacity of ribosomes to maintain the fidelity of translation in protein synthesis during aging. Elongation fidelity of ribosomes isolated from livers of young adult (6-10 months, n=9) and old (23-24 months, n=11) rats was assessed for poly(U) message through the error co-incorporation of leucine (Leu) with phenylalanine (Phe), using controlled rate measurements. No statistically significant difference in the error response of ribosomes from young and old animals was detected on manipulating magnesium. The maximum Phe and Leu rates occurred at approximately 8 and approximately 11 mM Mg2+, respectively; the relative error frequency (Leu/Phe ratio) at the Leu maximum was approximately 2%. The aminoglycoside paromomycin (PM) elicited a considerably higher degree of error incorporation: 12-14% Leu/Phe in the range of the Leu rate maximum, 40-60 microM paromomycin, at 9 mM Mg2+. A statistically significant increase was detected in the error frequency for ribosomes from old as compared with young animals (at p less than 0.02) between 20 and 60 microM paromomycin, the largest increase (approximately 9%) occurring at the Leu rate maximum. Also, the ribosomes from the old animals, in terms of the error frequency, were found to be significantly more sensitive to paromomycin concentration (at p less than 0.02) up to the Leu maximum. These results indicate that liver ribosomes of old rats may have a slightly decreased capacity to maintain fidelity, which can be expressed under particular conditions.