de Moraes Diogo, Paiva Brunno Vivone Buquete, Cury Sarah Santiloni, Ludwig Raissa Guimarães, Junior João Pessoa Araújo, Mori Marcelo Alves da Silva, Carvalho Robson Francisco
1Department of Structural and Functional Biology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
2Faculty of Medicine, São Paulo State University, UNESP, Botucatu, São Paulo, Brazil.
Aging Dis. 2021 Feb 1;12(1):42-49. doi: 10.14336/AD.2020.1112. eCollection 2021 Feb.
COVID-19 is prevalent in the elderly. Old individuals are more likely to develop pneumonia and respiratory failure due to alveolar damage, suggesting that lung senescence may increase the susceptibility to SARS-CoV-2 infection and replication. Considering that human coronavirus (HCoVs; SARS-CoV-2 and SARS-CoV) require host cellular factors for infection and replication, we analyzed Genotype-Tissue Expression (GTEx) data to test whether lung aging is associated with transcriptional changes in human protein-coding genes that potentially interact with these viruses. We found decreased expression of the gene tribbles homolog 3 () during aging in male individuals, and its protein was predicted to interact with HCoVs nucleocapsid protein and RNA-dependent RNA polymerase. Using publicly available lung single-cell data, we found expressed mainly in alveolar epithelial cells that express SARS-CoV-2 receptor ACE2. Functional enrichment analysis of age-related genes, in common with SARS-CoV-induced perturbations, revealed genes associated with the mitotic cell cycle and surfactant metabolism. Given that TRIB3 was previously reported to decrease virus infection and replication, the decreased expression of in aged lungs may help explain why older male patients are related to more severe cases of the COVID-19. Thus, drugs that stimulate TRIB3 expression should be evaluated as a potential therapy for the disease.
新冠病毒（COVID-19）在老年人中普遍流行。由于肺泡损伤，老年人更易患肺炎和呼吸衰竭，这表明肺衰老可能会增加对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染和复制的易感性。鉴于人类冠状病毒（HCoVs；SARS-CoV-2和SARS-CoV）感染和复制需要宿主细胞因子，我们分析了基因型-组织表达（GTEx）数据，以测试肺衰老是否与可能与这些病毒相互作用的人类蛋白质编码基因的转录变化相关。我们发现男性个体在衰老过程中 tribbles 同源物3（TRIB3）基因的表达降低，并且预测其蛋白质与HCoVs核衣壳蛋白和RNA依赖性RNA聚合酶相互作用。利用公开的肺单细胞数据，我们发现TRIB3主要在表达SARS-CoV-2受体血管紧张素转换酶2（ACE2）的肺泡上皮细胞中表达。与SARS-CoV引起的扰动共同进行的与年龄相关基因的功能富集分析，揭示了与有丝分裂细胞周期和表面活性剂代谢相关的基因。鉴于此前报道TRIB3可减少病毒感染和复制，老年肺中TRIB3表达降低可能有助于解释为什么老年男性患者与更严重的COVID-19病例相关。因此，应评估刺激TRIB3表达的药物作为该疾病的潜在治疗方法。
