Cardiac hypertrophy, aging and changes in cardiac ribosomal RNA gene dosage in man.

The dosage of ribosomal RNA genes was determined in left ventricular myocardium obtained from two young individuals (ages 18 and 20 years), and from three older individuals (ages 64, 73 and 75 years), two of whom were diagnosed to have left ventricular hypertrophy. The technique of RNA-DNA molecular hybridization was employed to determine the gene dosage. The results indicate that there is a significant decline in the dosage of ribosomal RNA genes in the myocardium from the older individuals; the average hybridization level (the parameter of gene dosage) was 0.096% (range: 0.092 to 0.100%) for the young myocardium, and 0.068% (range: 0.063 to 0.076%) for the older myocardium. Within the older age group the hybridization level for the one tissue judged to be non-hypertrophic was essentially identical in its dosage to the tissues derived from hypertrophic myocardium. These results, which are highly consistent with earlier studies on canine tissues, are interpreted to suggest that: (1) a ribosomal RNA gene loss such as that measured in aging myocardium may impose limitations on the rate of RNA synthesis, and thus indirectly cause abnormally low rates of protein synthesis within the myocardium during periods of stress, and (2) that such restrictions on the maximum rate of protein synthesis may account for the decreased ability of aged myocardium to respond to increased work loads, and the reduced contractility characteristic of aging muscle, hypertrophic myocardium and the failing heart.