Treatment with the senolytics dasatinib/quercetin reduces SARS-CoV-2-related mortality in mice

IF 8 1区医学 Q1 CELL BIOLOGY

Aging Cell Pub Date : 2023-01-26 DOI:10.1111/acel.13771

Andrés Pastor-Fernández, Antonio R. Bertos, Arantzazu Sierra-Ramírez, Javier del Moral-Salmoral, Javier Merino, Ana I. de ávila, Cristina Olagüe, Ricardo Villares, Gloria González-Aseguinolaza, María ángeles Rodríguez, Manuel Fresno, Nuria Gironés, Matilde Bustos, Cristian Smerdou, Pablo Jose Fernandez-Marcos, Cayetano von Kobbe

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引用次数: 4

Abstract

The enormous societal impact of the ongoing COVID-19 pandemic has been particularly harsh for some social groups, such as the elderly. Recently, it has been suggested that senescent cells could play a central role in pathogenesis by exacerbating the pro-inflammatory immune response against SARS-CoV-2. Therefore, the selective clearance of senescent cells by senolytic drugs may be useful as a therapy to ameliorate the symptoms of COVID-19 in some cases. Using the established COVID-19 murine model K18-hACE2, we demonstrated that a combination of the senolytics dasatinib and quercetin (D/Q) significantly reduced SARS-CoV-2-related mortality, delayed its onset, and reduced the number of other clinical symptoms. The increase in senescent markers that we detected in the lungs in response to SARS-CoV-2 may be related to the post-COVID-19 sequelae described to date. These results place senescent cells as central targets for the treatment of COVID-19, and make D/Q a new and promising therapeutic tool.

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用抗衰老药物达沙替尼/槲皮素治疗可降低小鼠sars - cov -2相关死亡率

正在进行的COVID-19大流行的巨大社会影响对老年人等一些社会群体尤其严重。最近有研究表明，衰老细胞可能通过加剧对SARS-CoV-2的促炎免疫反应在发病机制中发挥核心作用。因此，在某些情况下，抗衰老药物选择性清除衰老细胞可能有助于改善COVID-19的症状。使用已建立的COVID-19小鼠模型K18-hACE2，我们证明了抗衰老药物达沙替尼和槲皮素(D/Q)联合使用可显著降低sars - cov -2相关死亡率，延迟其发病，并减少其他临床症状的数量。我们在肺部检测到的针对SARS-CoV-2的衰老标志物的增加可能与迄今为止描述的covid -19后后遗症有关。这些结果使衰老细胞成为治疗COVID-19的中心靶点，并使D/Q成为一种新的有前途的治疗工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Aging Cell Biochemistry, Genetics and Molecular Biology-Cell Biology

自引率

2.60%

发文量

212

期刊介绍： Aging Cell is an Open Access journal that focuses on the core aspects of the biology of aging, encompassing the entire spectrum of geroscience. The journal's content is dedicated to publishing research that uncovers the mechanisms behind the aging process and explores the connections between aging and various age-related diseases. This journal aims to provide a comprehensive understanding of the biological underpinnings of aging and its implications for human health. The journal is widely recognized and its content is abstracted and indexed by numerous databases and services, which facilitates its accessibility and impact in the scientific community. These include: Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Academic Search Premier (EBSCO Publishing) Biological Science Database (ProQuest) CAS: Chemical Abstracts Service (ACS) Embase (Elsevier) InfoTrac (GALE Cengage) Ingenta Select ISI Alerting Services Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) Natural Science Collection (ProQuest) PubMed Dietary Supplement Subset (NLM) Science Citation Index Expanded (Clarivate Analytics) SciTech Premium Collection (ProQuest) Web of Science (Clarivate Analytics) Being indexed in these databases ensures that the research published in Aging Cell is discoverable by researchers, clinicians, and other professionals interested in the field of aging and its associated health issues. This broad coverage helps to disseminate the journal's findings and contributes to the advancement of knowledge in geroscience.