PROTEINS IMPLICATED IN CARDIAC SENESCENCE

心血管科学实验室致力于识别和研究心肌的衰老过程。为了鉴定心脏中可能与衰老有关的基因产物，我们用Fisher 344大鼠左心室的mRNA分析了cDNA微阵列。将12个月、18个月、24个月和30个月的样本进行比较。在作为年龄函数分析的9000多个独特cdna中，388个（4.3%）显示表达改变，其中平衡差异表达（BDE）大于2.0（下调）或小于-2.0（上调）。在388个序列中，有125个是未知的est。随着年龄的增长，丰度改变的转录本数量普遍增加，如下所示：12个月，1个增加(I)， 2个减少(D)；18月29 (I), 75 (D)；24月37 (I), 33 (D)；和30月。182 (I), 67 (D)。在丰度改变的388个转录本中，91%在一个时间点表现出表达变化，只有9%在两个以上年龄组中表现出变化。大多数在多个时间点显示表达改变的rna被归类为功能类别。数据表明，绝大多数转录本（大于95%）不随年龄变化。只有4.3%的转录本显示出年龄依赖性的改变，其中大多数发生在生命后期（64%，249/388发生在30个月）。其中47%（118/249）属于身份尚未确定的est。现在初步筛选已经完成，目的是确定基因表达随衰老过程变化的意义。为此，许多分子分析正在进行中，以确定哪些产物可能实际上参与了导致衰老过程的假设信号事件。

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.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, numerous molecular analyses are underway to identify which products may actually be involved in the hypothesized signal events responsible for the aging process.