Necrotic and apoptotic myocyte cell death in the aging heart of Fischer 344 rats.

Abstract

To determine the effects of aging on myocyte cell death, Fischer 344 rats at 3, 7, 12, 16, and 24 mo of age were injected with myosin monoclonal antibody for the localization and quantification of necrotic myocyte cell death in the left ventricle, interventricular septum, and right ventricle. Conversely, the presence of DNA strand breaks in myocyte nuclei, indicative of programmed cell death, was evaluated by the terminal deoxynucleotidyl transferase assay and confirmed by DNA laddering. Myocyte necrosis, which involved nearly 1,000 myocytes in the left ventricular free wall at 3 mo, progressively increased with aging, reaching a value of 13,600 myocytes at 24 mo. Corre- sponding values in the interventricular septum were 300 and 9,400 myocytes. In the right ventricle, there were 270 necrotic myocytes at 3 mo and 9,000 at 24 mo. Programmed myocyte cell death was restricted to the left ventricular free wall and included 140 cells at 3 mo. This form of myocyte cell death increased at the subsequent age intervals, resulting in the involvement of 874 cells at 24 mo. The combination of necrosis and apoptosis in the left ventricular free wall was associated with 1,150 cells dying at 3 mo and 14,500 at 24 mo. In conclusion, myocyte cell death, apoptotic and necrotic in nature, constitutes an important determinant of the aging process, possibly mediating the occurrence of ventricular dysfunction and failure in the old heart.