Effect of Age on Thyroxine-Induced Cardiac Hypertrophy in Mice1

Induction of cardiac hypertrophy by thyroxine was compared in adult (8 mo.) and old (26 mo.) euthyroid C57BI/6J mice. Hearts in old and adult animals ultimately exhibited the same percentage increases in heart/body weight ratio, and dose-response curves were identical, but there.was a sig-nificantly longer lag period before hypertrophy occurred in older mice. In both groups, increases in 3H-leucine incorporation into protein were observed prior to increases in heart/body weight ratios. We interpret these observations to indicate that lower protein synthetic rates in old hearts signal an impairment in adaptability which may contribute to the increased incidence of heart failure with age. and Florini (1972) found that the rate of protein synthesis was significantly lower in hearts from old (25 to 27 mo.) C57B1/ 6J mice than in those from adult (8 to 9 mo.) mice. However, there was no decrease in heart weight in the older animals, so presumably the rate of protein degradation changed in par-allel with the observed changes in the rate of protein synthesis. Furthermore, hearts from old animals were at least as active as those from young animals (1 to 3 mo.) when protein syn-thesis was measured in the perfusion system. Thus it was not obvious from the results of Geary and Florini (1972) that the decreased rate of protein synthesis in hearts of old mice could be correlated with the increased incidence of heart disease with age in human popula-tions. However, it occurred to us that hearts in old animals might be less responsive to stresses which normally cause increases in car-diac protein synthesis; i.e., old hearts might be relatively slow to synthesize additional contrac-tile tissue under conditions in which cardiac hypertrophy is essential for survival. We first attempted to induce hypertrophy by controlled 1 Supported by a grant from the Heart Association of Upstate Ne