Transcriptome Network Analysis Reveals Aging-Related Mitochondrial and Proteasomal Dysfunction and Immune Activation in Human Thyroid
Transcriptome Network Analysis Reveals Aging-Related Mitochondrial and Proteasomal Dysfunction and Immune Activation in Human Thyroid
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DOI：
10.1089/thy.2017.0359
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发表时间：
2018-04-23
期刊：
影响因子：
6.6
通讯作者：
Seo, Jeong-Sun
中科院分区：
文献类型：
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作者：
Cho, Byuri Angela;Yoo, Seong-Keun;Seo, Jeong-Sun
背景：阐明人体器官中与衰老相关的转录组变化对于了解衰老生理学和机制是必要的，但对甲状腺知之甚少。我们研究了人类甲状腺中与衰老相关的转录组变化，并表征了相关的分子功能。方法：对来自基因型-组织表达项目的 322 个甲状腺组织样本的公开 RNA 测序数据进行了分析。此外，我们还使用了我们自己的64个正常甲状腺组织样本的RNA测序数据作为验证集。为了全面评估衰老与转录组变化之间的关联，我们进行了加权基因共表达网络分析和通路富集分析。然后使用甲状腺分化评分进行进一步分析，确定甲状腺分化与衰老之间的相关性。结果：甲状腺中最显着的衰老相关转录组变化是与线粒体和蛋白酶体功能相关的基因下调（p = 3 x 10(-6)）。此外，与免疫过程相关的基因随着年龄的增长而显着上调（p = 3 x 10(-4)），并且所有这些基因都与受淋巴细胞性甲状腺炎影响的甲状腺中上调的基因重叠。此外，这些与衰老相关的变化在性别上没有显着差异，但就甲状腺分化而言，女性更容易受到衰老相关变化的影响（趋势p = 0.03）。结论：甲状腺中与衰老相关的转录组变化与线粒体和蛋白酶体功能障碍、分化丧失和自身免疫过程的激活有关。我们的研究结果为更好地了解与年龄相关的甲状腺功能下降和自身免疫性甲状腺疾病的易感性增加提供了线索。
Background: Elucidating aging-related transcriptomic changes in human organs is necessary to understand the aging physiology and mechanisms, but little is known regarding the thyroid gland. We investigated aging-related transcriptomic alterations in the human thyroid gland and characterized the related molecular functions.Methods: Publicly available RNA sequencing data of 322 thyroid tissue samples from the Genotype-Tissue Expression project were analyzed. In addition, our own 64 RNA sequencing data of normal thyroid tissue samples were used as a validation set. To comprehensively evaluate the associations between aging and transcriptomic changes, we performed a weighted gene coexpression network analysis and pathway enrichment analysis. The thyroid differentiation score was then used for further analysis, defining the correlations between thyroid differentiation and aging.Results: The most significant aging-related transcriptomic change in thyroid was the downregulation of genes related to the mitochondrial and proteasomal functions (p = 3 x 10(-6)). Moreover, genes that are associated with immune processes were significantly upregulated with age (p = 3 x 10(-4)), and all of them overlapped with the upregulated genes in the thyroid glands affected by lymphocytic thyroiditis. Furthermore, these aging-related changes were not significantly different according to sex, but in terms of the thyroid differentiation, females were more susceptible to aging-related changes (p for trend = 0.03).Conclusions: Aging-related transcriptomic changes in the thyroid gland were associated with mitochondrial and proteasomal dysfunction, loss of differentiation, and activation of autoimmune processes. Our results provide clues to better understanding the age-related decline in thyroid function and higher susceptibility to autoimmune thyroid disease.