Abstract 16878: Cardiomyogenesis in the Aging and Failing Human Heart
The extent of myocyte formation occurring physiologically and pathologically is controversial. Recently, based on the integration of atmospheric 14C into DNA, the turnover of myocytes in the human heart has been claimed to involve 1% of cells annually in young individuals, decreasing to 0.45% with age. This low degree of myocyte renewal is inconsistent with the rate of myocyte death present in the aging and diseased human heart. Because of the numerous limitations in the early study, we performed retrospective 14C birth dating of myocytes isolated from 19 donor hearts, 2-78 years of age, and 17 explanted failing hearts, 22-70 years of age. This magnitude of sampling was introduced to define the effects of aging and disease on myocyte regeneration. The purity of each cell preparation was determined first to correct the values of 14C in myocytes of each heart for the contribution of non-myocytes. Also, the proportion of mononucleated and multinucleated myocytes was measured and introduced in the evaluation of the 14C data. A critical parameter for the interpretation of 14C in the DNA involves the level of polyploidy, which mimics cell replication, resulting in an overestimation of the rate of myocyte turnover. The analysis of ploidy by flow cytometry showed that the majority of myocyte nuclei had a diploid DNA content. Despite its limited contribution, the value of polyploidy in each heart was introduced. From 2 to 20 years and from 33 to 63 years, myocyte age averaged ∼3 and ∼7 years, respectively. From 68 to 78 years, myocyte age decreased to a value of 2.6 years. Thus, myocyte age increased postnatally, remained relatively constant in adulthood, and decreased in the old heart. From 2 to 20 years, annual myocyte renewal comprised 23% of cells, and from 20 to 40 years, 7% of cells. Subsequently, myocyte replacement increased with age; at 50, 60, 70, and 80 years, myocyte formation involved annually 8%, 10%, 14%, and 19% of cells, respectively. From 20 to 78 years of age, the adult human heart replaces ∼8 times its entire myocyte compartment, and myocyte regeneration is further enhanced with chronic heart failure (CHF). In conclusion, retrospective 14C birth dating demonstrated that the human heart etains a remarkable degree of plasticity throughout life and in the presence of CHF.
- © 2012 by American Heart Association, Inc.