Abstract 17367: Myocyte Turnover in the Aging Human Heart
The controversy on the growth reserve of the adult human heart has not been resolved and the extent of myocyte renewal reported by different laboratories varies significantly. Additionally, myocyte regeneration has been claimed to decrease with aging which is inconsistent with the high degree of cell death present in the old myocardium. Thus, the effects of age and gender on the magnitude of myocyte turnover were determined in 32 and 42 female and male hearts, respectively. Myocyte replication, senescence and death were measured in normal female and male human hearts collected from patients 19 to 104 years of age who died from causes other than cardiovascular diseases. Myocardial aging was characterized by a time-dependent increase in the generation of amplifying cardiomyocytes in women and men. Levels of Ki67 and phospho-H3 were comparable in the young female and male heart but differed later in life. As a function of age, the pool of amplifying myocytes was 2-fold higher in women than men, pointing to enhanced myocyte renewal in the female heart. The frequency of p16INK4a-positive myocytes was higher in men than in women. From 19 to 104 years of age, the time-dependent increase in senescent myocytes was 0.68% per year in women and 0.89% per year in men; the 31% higher rate of accumulation of old myocytes in the aging male heart was significant. Myocyte apoptosis occurred only in p16INK4a-positive cells and was consistently higher in men than in women at all ages. However, the increase in myocyte apoptosis with age did not differ with gender. Subsequently, we measured the average age of cardiomyocytes, their age distribution, turnover rate and time to acquire the senescent phenotype to define the biology of myocardial aging. In the female heart, myocyte turnover occurred at a rate of 10%, 15% and 40% per year at 20, 60 and 100 years of age, respectively. Corresponding values in the male heart were 7%, 12% and 32% per year, documenting that cardiomyogenesis involves a large and progressively increasing number of parenchymal cells with aging. In conclusion, the human heart is a highly dynamic organ in which myocyte loss is counteracted in part by myocyte renewal. Myocyte regeneration during physiological aging takes place at previously unexpected levels in both women and men.
- © 2010 by American Heart Association, Inc.