Ageing in man is associated with changes to the splicing factor pool. A proportion of splicing factors are regulated during ageing by mechanisms involving the Ataxia Telangiectasia Mutated (ATM) gene, but the factors that determine the remaining proportion have yet to be identified. DNA methylation is known to be an important regulatory mechanism of gene expression. We assessed age-associated methylation and expression levels for 27 splicing factor genes, in peripheral blood samples from the InCHIANTI study. Examination of splicing patterns at specific loci was examined in a second cohort, the Exeter 10000 study. 27/502 methylation probes in 17 different genes were associated with age. Most changes were not associated with transcript expression levels or splicing patterns, but hypomethylation of the SF3B1 promoter region was found to mediate 53% of the relationship between age and transcript expression at this locus (p=0.02). DNA methylation does not appear to play a major role in regulation of the splicing factors, but changes in SF3B1 expression may be attributable to promoter hypomethylation at this locus. SF3B1 encodes a critical component of the U2 snRNP; altered expression of this gene may therefore contribute to the loss of regulated mRNA splicing that occurs with age.

中文翻译：

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剪接因子 3B1 低甲基化与老年人 SF3B1 转录本表达的改变有关。

人的衰老与剪接因子库的变化有关。一部分剪接因子在衰老过程中通过涉及共济失调毛细血管扩张症 (ATM) 基因的机制进行调节，但决定剩余比例的因素尚未确定。众所周知，DNA 甲基化是基因表达的重要调控机制。我们评估了来自 InCHIANTI 研究的外周血样本中 27 个剪接因子基因的年龄相关甲基化和表达水平。在第二个队列 Exeter 10000 研究中检查了特定位点的剪接模式。17 个不同基因中的 27/502 甲基化探针与年龄相关。大多数变化与转录本表达水平或剪接模式无关，但发现 SF3B1 启动子区域的低甲基化介导了该位点年龄和转录本表达之间 53% 的关系（p=0.02）。DNA 甲基化似乎在剪接因子的调节中没有发挥主要作用，但 SF3B1 表达的变化可能归因于该位点的启动子低甲基化。SF3B1 编码 U2 snRNP 的关键组成部分；因此，该基因表达的改变可能导致随着年龄增长而发生的受调控的 mRNA 剪接的丧失。