Leydig cell gene expression: effects of age and caloric restriction
Leydig cell gene expression: effects of age and caloric restriction
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DOI：
10.1016/j.exger.2003.09.021
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发表时间：
2004-01-01
影响因子：
3.9
通讯作者：
Zirkin, BR
中科院分区：
文献类型：
--
作者：
Chen, HL;Irizarry, RA;Zirkin, BR
在哺乳动物中，血清中睾酮的浓度通常随着年龄的增长而降低。我们已经证明，在大鼠中，这是由于单个Leydig细胞的睾酮产生减少所致。为了了解Leydig细胞类固醇生成功能随年龄变化的机制，我们比较了从年轻和年老的Brown Norway大鼠分离的Leydig细胞中的基因表达谱，重点关注参与类固醇生成或与类固醇生成相关的基因的可能变化。我们还探讨了热量限制对这些基因表达的影响，热量限制是一种干预措施，可以延迟或抑制许多系统和生物体中与年龄相关的病理和生物学变化。在我们使用的每组五个膜上排列的总共1176个基因中，约500个（45%）在从年轻和老年大鼠睾丸分离的Leydig细胞中检测到，在两个年龄段的细胞中检测到相同的基因。应用ANOVA模型统计分析四个处理组中的500个可检测基因。选择感兴趣基因的主要标准是P值小于或等于0.05。随着年龄的增长，大量基因的倍数变化> 1.5。然而，当P值小于或等于0.05作为选择标准时，只有45个基因随年龄变化显著。这些基因中的大多数（但不是全部）也具有> 1.5的倍数变化。在500个基因中，发现17个基因的表达随着年龄的增长而减少，其中最突出的是参与类固醇生成和应激反应/自由基清除的基因。长期的热量限制对年龄改变的45个基因几乎没有影响。与在许多其他细胞类型和系统中看到的热量限制的影响相反，绝大多数（44/45）随年龄变化的Leydig细胞基因并没有被这种干预“拯救”。(C)2003年爱思唯尔公司All rights reserved.
In mammals, the concentration of testosterone in blood serum typically becomes reduced with aging. We have shown that, in rats, this results from reduced testosterone production by individual Leydig cells. To gain an understanding of the mechanisms by which Leydig cell steroidogenic function changes with aging, we compared the gene expression profiles in Leydig cells isolated from young and old Brown Norway rats, focusing on possible changes in genes involved in, or associated with, steroidogenesis. We also explored the effects of caloric restriction, an intervention shown to delay or inhibit age-associated pathologic and biologic changes in a number of systems and organisms, on the expression of these genes. Of the total of 1176 genes arrayed on each of the five membranes per group that we used, about 500 (45%) were detectable in Leydig cells isolated from young and old rat testes, with the same genes detectable in cells from both ages. An ANOVA model was applied to statistically analyze the 500 detectable genes in the four treatment groups. The primary criterion by which interesting genes were selected was a P value of less than or equal to 0.05. With aging, a large number of genes were seen with fold changes of > 1.5. However, when P less than or equal to 0.05 was used as the selection criterion, only 45 genes were seen to change significantly with age. Most, but not all, of these genes also had fold changes of > 1.5. Among the 500 genes, 17 were found to decrease in expression with aging, the most prominent among which were genes involved in steroidogenesis and stress response/free radical scavenging. Long-term caloric restriction had little effect on the 45 genes altered by age. In contrast to the effects of caloric restriction as seen in many other cell types and systems, the vast majority (44/45) of the Leydig cell genes that changed with age were not 'rescued' by this intervention. (C) 2003 Elsevier Inc. All rights reserved.