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Transcriptome analysis reveals the difference between "healthy" and "common" aging and their connection with age-related diseases.
Aging Cell ( IF 8.0 ) Pub Date : 2020-02-19 , DOI: 10.1111/acel.13121 Lu Zeng 1 , Jialiang Yang 1 , Shouneng Peng 1 , Jun Zhu 1 , Bin Zhang 1 , Yousin Suh 2 , Zhidong Tu 1
Aging Cell ( IF 8.0 ) Pub Date : 2020-02-19 , DOI: 10.1111/acel.13121 Lu Zeng 1 , Jialiang Yang 1 , Shouneng Peng 1 , Jun Zhu 1 , Bin Zhang 1 , Yousin Suh 2 , Zhidong Tu 1
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A key goal of aging research was to understand mechanisms underlying healthy aging and develop methods to promote the human healthspan. One approach is to identify gene regulations unique to healthy aging compared with aging in the general population (i.e., “common” aging). Here, we leveraged Genotype‐Tissue Expression (GTEx) project data to investigate “healthy” and “common” aging gene expression regulations at a tissue level in humans and their interconnection with diseases. Using GTEx donors' disease annotations, we defined a “healthy” aging cohort for each tissue. We then compared the age‐associated genes derived from this cohort with age‐associated genes from the “common” aging cohort which included all GTEx donors; we also compared the “healthy” and “common” aging gene expressions with various disease‐associated gene expressions to elucidate the relationships among “healthy,” “common” aging and disease. Our analyses showed that 1. GTEx “healthy” and “common” aging shared a large number of gene regulations; 2. Despite the substantial commonality, “healthy” and “common” aging genes also showed distinct function enrichment, and “common” aging genes had a higher enrichment for disease genes; 3. Disease‐associated gene regulations were overall different from aging gene regulations. However, for genes regulated by both, their regulation directions were largely consistent, implying some aging processes could increase the susceptibility to disease development; and 4. Possible protective mechanisms were associated with some “healthy” aging gene regulations. In summary, our work highlights several unique features of GTEx “healthy” aging program. This new knowledge could potentially be used to develop interventions to promote the human healthspan.
中文翻译：
转录组分析揭示了“健康”衰老和“普通”衰老之间的差异及其与年龄相关疾病的联系。
衰老研究的一个关键目标是了解健康衰老的机制并开发促进人类健康寿命的方法。一种方法是确定与一般人群的衰老（即“常见”衰老）相比，健康衰老所特有的基因调控。在这里，我们利用基因型组织表达（GTEx）项目数据来研究人类组织水平上的“健康”和“常见”衰老基因表达调控及其与疾病的相互关系。使用 GTEx 捐赠者的疾病注释，我们为每个组织定义了一个“健康”衰老队列。然后，我们将来自该队列的年龄相关基因与来自“普通”衰老队列（包括所有 GTEx 捐赠者）的年龄相关基因进行了比较；我们还将“健康”和“常见”衰老基因表达与各种疾病相关基因表达进行了比较，以阐明“健康”、“常见”衰老和疾病之间的关系。我们的分析表明，1. GTEx“健康”和“普通”衰老共享大量基因调控；2.尽管存在实质性共性，但“健康”和“常见”衰老基因也表现出明显的功能富集，“常见”衰老基因对疾病基因的富集程度较高；3.疾病相关基因调控与衰老基因调控总体不同。然而，对于两者调控的基因来说，它们的调控方向基本一致，这意味着某些衰老过程可能会增加疾病发生的易感性；4.可能的保护机制与一些“健康”衰老基因调控有关。总之，我们的工作突出了 GTEx“健康”老龄化计划的几个独特之处。这一新知识有可能用于制定干预措施，以促进人类健康寿命。
更新日期：2020-02-19
中文翻译：
转录组分析揭示了“健康”衰老和“普通”衰老之间的差异及其与年龄相关疾病的联系。
衰老研究的一个关键目标是了解健康衰老的机制并开发促进人类健康寿命的方法。一种方法是确定与一般人群的衰老（即“常见”衰老）相比，健康衰老所特有的基因调控。在这里，我们利用基因型组织表达（GTEx）项目数据来研究人类组织水平上的“健康”和“常见”衰老基因表达调控及其与疾病的相互关系。使用 GTEx 捐赠者的疾病注释，我们为每个组织定义了一个“健康”衰老队列。然后，我们将来自该队列的年龄相关基因与来自“普通”衰老队列（包括所有 GTEx 捐赠者）的年龄相关基因进行了比较；我们还将“健康”和“常见”衰老基因表达与各种疾病相关基因表达进行了比较，以阐明“健康”、“常见”衰老和疾病之间的关系。我们的分析表明，1. GTEx“健康”和“普通”衰老共享大量基因调控；2.尽管存在实质性共性，但“健康”和“常见”衰老基因也表现出明显的功能富集，“常见”衰老基因对疾病基因的富集程度较高；3.疾病相关基因调控与衰老基因调控总体不同。然而，对于两者调控的基因来说，它们的调控方向基本一致，这意味着某些衰老过程可能会增加疾病发生的易感性；4.可能的保护机制与一些“健康”衰老基因调控有关。总之，我们的工作突出了 GTEx“健康”老龄化计划的几个独特之处。这一新知识有可能用于制定干预措施，以促进人类健康寿命。
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