Age-related alterations in cardiac protein turnover

The influence of aging on cardiac protein turnover in rats was studied in vitro and in vivo. Hearts were perfused in vitro on a modified Langendorff perfusion apparatus with buffer containing cycloheximide to inhibit protein synthesis, and the rate of phenylalanine release into the perfusate was measured as an index of protein degradation. Phenylalanine release from hearts of 1- to 2 1 2-month-old rats was 0.22 ± 0.013 nmol/mg wet wt/h compared to 0.16 ± 0.011 nmol/mg/h from hearts of 10- to 14-month-old animals (P < 0.005). This represents a 27% decrease in the rate of cardiac protein degradation in perfused hearts of older rats. When insulin was present in the perfusate the difference in cardiac protein degradation rates between animals in these age groups was similar (21% decrease in older animals, P < 0.01). Protein turnover in vivo was measured by the constant infusion technique using [¹⁴C]tyrosine. The fractional rate of cardiac protein degradation decreased from 14.8 ± 1.06%/day at 1 1 2 months of age to 10.8 ± 0.91%/day at 12 months of age (P < 0.05). The rate of protein synthesis was also slower in the older rats, decreasing from 19.6 ± 1.63%/day at 1 1 2 months to 10.8 ± 0.91%/day at 12 months (P < 0.005). In senile (24-month-old) hooded rats the fractional rates of cardiac protein synthesis and degradation were further reduced to 6.7 ± 0.29%/day compared to 12.4 ± 0.61%/day for 12-month-old rats of the same strain (P < 0.005). Thus, we conclude that cardiac protein degradation and synthesis decrease with aging.