NECROTIC AND APOPTOTIC MYOCYTE CELL-DEATH IN THE AGING HEART OF FISCHER-344 RATS

To determine the effects of aging on myocyte cell death, Fischer 344 r ats at 3, 7, 12, 16, and 24 mo of age were injected with myosin monocl onal antibody for the localization and quantification of necrotic myoc yte cell death in the left ventricle, interventricular septum, and rig ht ventricle. Conversely, the presence of DNA strand breaks in myocyte nuclei, indicative of programmed cell death, was evaluated by the ter minal deoxynucleotidyl transferase assay and confirmed by DNA ladderin g. Myocyte necrosis, which involved nearly 1,000 myocytes in the left ventricular free wall at 3 mo, progressively increased with aging, rea ching a value of 13,600 myocytes at 24 mb. Corresponding values in the interventricular septum were 300 and 9,400 myocytes. In the right ven tricle, there were 270 necrotic myocytes at 3 mo and 9,000 at 24 mo. P rogrammed myocyte cell death was restricted to the left ventricular fr ee wall and included 140 cells at 3 mo. This form of myocyte cell deat h increased at the subsequent age intervals, resulting in the involvem ent of 874 cells at 24 mo. The combination of necrosis and apoptosis i n 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, apopt otic and necrotic in nature, constitutes an important determinant of t he aging process, possibly mediating the occurrence of ventricular dys function and failure in the old heart.