Effects of aging on regional rates of cerebral protein synthesis in the Sprague-Dawley rat: examination of the influence of recycling of amino acids derived from protein degradation into the precursor pool

Abstract

The quantitative autoradiographic l-[1- 14C]leucine method for determination of regional rates of cerebral protein synthesis (1CPS leu) requires knowledge of the degree of recycling of leucine derived from protein degradation into the precursor pool for protein synthesis. The influence of recycling can be evaluated by measuring λ, the steady state ratio of the leucine specific activity in the precursor amino acid pool (tRNA-bound leucine) to that in the arterial plasma. To define the changes in 1CPS leu during the process of normal aging in the rat we have evaluated λ in middle-aged (14 months) and aged (24 months) rats and compared its values with those obtained previously in young adult rats (two months of age). The results show that the value of λ is the same in all three age groups, and that there is no change with aging in the fraction of leucine in the precursor pool derived from protein degradation. Our previously reported regional rates of protein synthesis in young adult and aged rats were based on the assumption that there was no recycling of leucine derived from protein degradation into the precursor pool for protein synthesis [Ingvar M. C., Maeder P., Sokoloff L. and Smith C. B. (1985) Brain 108, 155–170]. These values have been recalculated in the present study in order to take into account the appropriate correction for recycling. The recalculated rates are higher than those reported previously, but the effects of aging in the brain as a whole and in some specific brain regions are confirmed. Decreased 1CPS leu was observed by middle-age, and in this cross-sectional study did not appear to decrease further. Of the 39 brain regions examined decreases were found throughout the brain with some proclivity for the brain stem. In comparison with young adults the weighted average rate of protein synthesis in the brain as a whole was found to be decreased by 16 and 11 % in the middle-aged and aged groups, respectively.