Effects of age on myosin and creatine kinase isoforms in left ventricles of Fischer 344 rats

Left ventricles of hearts from male Fischer 344 rats of 2, 8 and 23 months of age were analyzed to determine if aging results in significant alterations in the isoform distribution of myosin and creatine kinase protein and mRNAs. Left ventricles of maturing (2-month) rats contained almost exclusively alpha-myosin heavy chain (MHC) mRNA and protein. In adults (8 months) there was a 5-fold increase in beta-MHC (fetal isoform) and an approximate 10% decrease in alpha-MHC mRNA levels, relative to 2 months. By 23 months (senescence), beta-MHC mRNA levels had increased by 11-fold and alpha-MHC mRNA levels had decreased by about 30%. These changes corresponded to an increase in the relative proportion of beta-MHC protein, from undetectable levels at 2 months, to about 40% by 8 months and to about 60% by 23 months. Increased levels of beta-MHC and its mRNA in older rats correlated with decreased serum thyroid hormone levels. The specific activity of creatine kinase in crude homogenates decreased with age, as has been reported previously. Relative to 2-month controls, the specific activity of creatine kinase had decreased by 21% at 8 months and by 37% at 23 months. Analysis of creatine kinase activity showed no large increase in levels of the fetal (B) isoform with age, as was found for myosin. Levels of mRNAs encoding the B and M isoforms of creatine kinase were significantly reduced in senescent rats. Thus, the decreased levels of creatine kinase in aging rats is correlated with decreased levels of mRNA encoding the BCK and MCK isoforms but not an isoform shift.