Bodyak Natalya, Kang Peter M, Hiromura Makoto, Sulijoadikusumo Indra, Horikoshi Nobuo, Khrapko Konstantin, Usheva Anny
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Nucleic Acids Res. 2002 Sep 1;30(17):3788-94. doi: 10.1093/nar/gkf497.
Heart disease remains the most frequent cause of death in the general population with increasing incidence in the elderly population. The pathologic failure of the aging heart may be related to structural and functional alterations in cardiac muscle cells. However, the molecular mechanisms underlying the aging-related decline in cardiac muscle function are largely unknown. To provide the first analysis of cardiac aging at the level of gene expression, we established and compared cDNA libraries from apparently healthy young and aged mouse ventricular cardiac muscle cells. We report the identification of genes that exhibit aging-related changes of mRNA levels. Aging expression profiles in aged hearts indicate decreased cellular adaptation and protection against stress-induced injury together with the development of contractile dysfunction. The data suggest reduced activity of the mitochondrial electron transport system and reduced levels of cardiac-specific transcription regulators. The cardiomyocyte aging profile of gene expression displays similarities with known heart disorders. Genes whose mRNA levels change with aging in cardiomyocytes might profoundly affect pathological changes in the heart.
心脏病仍然是普通人群中最常见的死亡原因,且在老年人群中的发病率不断上升。衰老心脏的病理衰竭可能与心肌细胞的结构和功能改变有关。然而,心肌功能随衰老而下降的分子机制在很大程度上尚不清楚。为了在基因表达水平上首次分析心脏衰老,我们建立并比较了来自明显健康的年轻和老年小鼠心室心肌细胞的cDNA文库。我们报告了鉴定出的显示mRNA水平与衰老相关变化的基因。老年心脏中的衰老表达谱表明细胞适应性和对应激诱导损伤的保护作用降低,同时出现收缩功能障碍。数据表明线粒体电子传递系统的活性降低以及心脏特异性转录调节因子的水平降低。心肌细胞衰老的基因表达谱与已知的心脏疾病相似。心肌细胞中mRNA水平随衰老而变化的基因可能会深刻影响心脏的病理变化。