Age and gender effects on cardiomyocyte apoptosis in the normal human heart.
Animal studies have suggested that apoptosis could play a significant role in the myocardial aging process. Although no information is available in humans, the paradigm that cardiomyocyte apoptosis is increased in the aged human heart has been widely propagated. Moreover, it is unknown whether gender differences may influence cardiomyocyte apoptosis. Cardiomyocyte apoptosis was compared between subjects ranging in age from 21 to 93 years (22 men and 19 women), free of any cardiovascular disease, who died of either violent or natural causes. Strict inclusion and exclusion criteria were used to ensure that the selected hearts accurately represented normal aging. Apoptosis was detected using the TdT-mediated dUTP digoxigenin nick end labeling (TUNEL) technique (controls for TUNEL included negative staining for splicing factor SC-35 and for Ki-67 antigen). The percentage of cardiomyocyte death ranged from 0% to 0.0437%, with no correlation with the age of the subject (p =.85). However, the percentage of apoptosis was threefold higher in men than in women (0.0133% +/- 0.0030% vs 0.0042% +/- 0.0008%, respectively; p <.01). Our results in humans do not support the hypothesis that aging influences the percentage of cardiomyocyte apoptosis. However, gender appears to be an important determinant of the occurrence of apoptosis.