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Transcriptome analysis of mouse aortae reveals multiple novel pathways regulated by aging

机译:小鼠Aortae的转录组分析显示出通过老化调节的多种新途径

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摘要

Vascular aging has been documented as a vital process leading to arterial dysfunction and age-related cardiovascular and cerebrovascular diseases. However, our understanding of the molecular underpinnings of age-related phenotypes in the vascular system is incomplete. Here we performed bulk RNA sequencing in young and old mouse aortae to elucidate age-associated changes in the transcriptome. Results showed that the majority of upregulated pathways in aged aortae relate to immune response, including inflammation activation, apoptotic clearance, and phagocytosis. The top downregulated pathway in aged aortae was extracellular matrix organization. Additionally, protein folding control and stress response pathways were downregulated in the aged vessels, with an array of downregulated genes encoding heat shock proteins (HSPs). We also found that circadian core clock genes were differentially expressed in young versus old aortae. Finally, transcriptome analysis combined with protein expression examination and smooth muscle cell (SMC) lineage tracing revealed that SMCs in aged aortae retained the differentiated phenotype, with an insignificant decrease in SMC marker gene expression. Our results therefore unveiled critical pathways regulated by arterial aging in mice, which will provide important insight into strategies to defy vascular aging and age-associated vascular diseases.
机译:血管衰老已被记录为导致动脉功能障碍和年龄相关的心血管和脑血管疾病的重要过程。然而,我们对血管系统中与年龄相关表型的分子下缺陷的理解是不完整的。在这里,我们在年轻和旧的小鼠Aortae中进行了批量RNA测序,以阐明转录组中的年龄相关变化。结果表明,老年血管症的大多数上调途径与免疫应答有关,包括炎症激活,凋亡清除和吞噬作用。 Aged Aortae的顶部下调途径是细胞外基质组织。另外,在老化容器中下调蛋白质折叠控制和应力响应途径,其中编码热休克蛋白(HSP)的下调基因阵列。我们还发现,昼夜节律核心时钟基因在年轻与旧的Aortae中差异表达。最后,转录组分析与蛋白质表达检查和平滑肌细胞(SMC)谱系追踪表明,老化Aortae中的SMCS保留了分化表型,SMC标记基因表达的微不足道。因此,我们的结果揭开了通过在小鼠中动脉衰老调节的关键途径,这将为缺乏血管老化和年龄相关的血管疾病的策略提供重要的洞察。

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