Department of Anesthesia and Medicine and Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Circ Res. 2010 Nov 26;107(11):1374-86. doi: 10.1161/CIRCRESAHA.110.231498. Epub 2010 Nov 18.
The turnover of cardiomyocytes in the aging female and male heart is currently unknown, emphasizing the need to define human myocardial biology.
The effects of age and gender on the magnitude of myocyte regeneration and the origin of newly formed cardiomyocytes were determined.
The interaction of myocyte replacement, cellular senescence, growth inhibition, and apoptosis was measured in normal female (n=32) and male (n=42) human hearts collected from patients 19 to 104 years of age who died from causes other than cardiovascular diseases. A progressive loss of telomeric DNA in human cardiac stem cells (hCSCs) occurs with aging and the newly formed cardiomyocytes inherit short telomeres and rapidly reach the senescent phenotype. Our data provide novel information on the superior ability of the female heart to sustain the multiple variables associated with the development of the senescent myopathy. At all ages, the female heart is equipped with a larger pool of functionally competent hCSCs and younger myocytes than the male myocardium. The replicative potential is higher and telomeres are longer in female hCSCs than in male hCSCs. In the female heart, myocyte turnover occurs at a rate of 10%, 14%, and 40% per year at 20, 60, and 100 years of age, respectively. Corresponding values in the male heart are 7%, 12%, and 32% per year, documenting that cardiomyogenesis involves a large and progressively increasing number of parenchymal cells with aging. From 20 to 100 years of age, the myocyte compartment is replaced 15 times in women and 11 times in men.
The human heart is a highly dynamic organ regulated by a pool of resident hCSCs that modulate cardiac homeostasis and condition organ aging.
目前尚不清楚衰老女性和男性心脏中心肌细胞的更新频率，这凸显了定义人类心肌生物学特性的必要性。
本研究旨在确定年龄和性别对心肌细胞再生程度和新形成的心肌细胞起源的影响。
本研究检测了来自因非心血管疾病死亡的年龄为 19 至 104 岁的男性（n=42）和女性（n=32）患者的正常心脏中的心肌细胞替换、细胞衰老、生长抑制和细胞凋亡之间的相互作用。随着年龄的增长，人心脏干细胞（hCSCs）中的端粒 DNA 逐渐丢失，新形成的心肌细胞继承了短端粒并迅速呈现衰老表型。我们的数据提供了有关女性心脏维持与衰老性肌病发展相关的多种变量的卓越能力的新信息。在所有年龄段，女性心脏都具有比男性心肌更大的功能成熟 hCSC 池和更年轻的心肌细胞。女性 hCSC 的复制潜能更高，端粒更长。在女性心脏中，心肌细胞的更新速度分别为每年 10%、14%和 40%，对应的年龄分别为 20 岁、60 岁和 100 岁；而在男性心脏中，心肌细胞的更新速度分别为每年 7%、12%和 32%，对应的年龄分别为 20 岁、60 岁和 100 岁，这表明心肌发生涉及到随着年龄的增长，越来越多的实质细胞参与其中。从 20 岁到 100 岁，女性的心肌细胞池更新了 15 次，男性更新了 11 次。
人类心脏是一个高度动态的器官，由一群调节心脏内稳态和器官衰老的常驻 hCSC 调节。
