Proteins Implicated In Cardiac Senescence

与心脏衰老有关的蛋白质

• 批准号: 6508399
• 负责人: Kenneth R Boheler
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6508399
• 关键词: aging; cardiac myocytes; cell senescence; developmental genetics; gene expression; laboratory rat; microarray technology; muscle proteins; myocardium

The Laboratory of Cardiovascular Science has a strong commitment to identifying and studying the process of aging in the myocardium. To identify gene products in heart potentially involved in aging, cDNA microarrays were analyzed with mRNA from left ventricles of Fisher 344 rats. Samples from 12, 18, 24 and 30 months were compared with those from 6 months. Of over 9000 unique cDNAs analyzed as a function of age, 388 (4.3%) showed altered expresson where the balanced differential expression (BDE) was greater than 2.0 (down-regulated) or less than -2.0 (up-regulated). Of the 388 sequences, 125 were unknown ESTs. The number of transcripts with altered abundances generally increased with aging and were as follows: 12 mo. 1 increased (I) and 2 decreased (D); 18 mo. 29 (I), 75 (D); 24 mo. 37 (I), 33 (D); and 30 mo. 182 (I), 67 (D). Of the 388 transcripts with altered abundance, 91% showed changes in expression at one time point, and only 9% showed changes in more than two age groups. Most of the RNAs showing altered expression at multiple time points have been grouped into functional categories. The data indicate that the vast majority of transcripts (greater than 95%) do not change with aging. Only 4.3% of the transcripts showed age-dependent alterations, most of which occurred late in life (64%, 249/388 occurred at 30 months). Of these, 47% (118/249) corresponded to ESTs whose identity remain to be determined. We have now completed an extensive quantitative-PCR analysis to identify gene products whose expression is altered in aging and eliminated numerous false positives. Now that the initial screening has been completed, the aim is to determine the significance of the changes in gene expression with the aging process. For this, molecular analyses are underway to identify which products may actually be involved in the hypothesized signal events responsible for the aging process. As a corollary to this project, we have begun and are near completion of an additional microarray analysis of human control and failing hearts. The data are being compared with that generated in the aging model to identify candidate genes implicated not only in aging, but also in disease.

心血管科学实验室对识别和研究心肌衰老的过程有坚定的承诺。为了鉴定潜在参与衰老的心脏中的基因产物，用Fisher 344大鼠的左心室中分析了cDNA微阵列。将12、18、24和30个月的样本与6个月的6个月进行了比较。在9000多个由年龄的函数分析的超过9000个独特的cDNA中，有388（4.3％）显示了平衡差分表达（BDE）大于2.0（下调）或小于-2.0（上调）的变化。在388个序列中，有125个是未知的EST。随着年龄的增长，丰度变化的转录本的数量通常如下：12 mo。 1增加（i）和2降低（d）； 18 mo。 29（i），75（d）; 24 mo。 37（i），33（d）;和30 mo。 182（i），67（d）。在388个具有变化丰度的转录本中，有91％的人在一个时间点显示表达变化，只有9％的年龄组显示出变化。大多数在多个时间点显示表达变化的RNA已将其分为功能类别。数据表明，绝大多数成绩单（大于95％）不会随着衰老而变化。只有4.3％的成绩单显示出年龄的变化，其中大多数发生在生命后期（64％，249/388发生在30个月时）。其中，47％（118/249）对应于其身份尚待确定的EST。现在，我们已经完成了广泛的定量PCR分析，以鉴定其在衰老中的表达改变并消除了许多假阳性的基因产物。现在，最初的筛选已经完成，目的是确定基因表达变化与衰老过程的重要性。为此，正在进行分子分析，以确定哪些产品实际上可能与负责老化过程的假设信号事件有关。作为该项目的推论，我们已经开始，几乎完成了对人类控制和失败心脏的其他微阵列分析。将数据与衰老模型中产生的数据进行了比较，以鉴定不仅与衰老有关的候选基因，而且还涉及疾病。