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斑马鱼心脏衰老过程中的功能改变和转录组变化。

Functional alterations and transcriptomic changes during zebrafish cardiac aging.

机构信息

Department of Genetics and Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.

Department of Biostatistics and Computational Biology, School of Life Sciences, Fudan University, Shanghai, China.

出版信息

Biogerontology. 2020 Oct;21(5):637-652. doi: 10.1007/s10522-020-09881-z. Epub 2020 May 5.

DOI:10.1007/s10522-020-09881-z
PMID:32372324
Abstract

Aging dramatically increases the risk of cardiovascular diseases in human. Animal models are of great value to study cardiac aging, and zebrafish have become a popular model for aging study recently. However, there is limited knowledge about the progression and regulation of cardiac aging in zebrafish. In this study we first validated the effectiveness of a panel of aging-related markers and revealed their spatial-temporal specificity. Using these markers, we discovered that cardiac aging in zebrafish initiated at mid-age around 24 months, followed by a gradual progression marked with increased DNA damage, inflammatory response and reduced mitochondrial function. Furthermore, we showed aging-related expression profile change in zebrafish hearts was similar to that in rat hearts. Overall, our results provide a deeper insight into the cardiac aging process in zebrafish, which will set up foundation for generating novel cardiac aging models suitable for large scale screening of pharmaceutical targets.

摘要

衰老大幅增加了人类患心血管疾病的风险。动物模型对于研究心脏衰老具有重要价值,而斑马鱼最近已成为衰老研究的热门模型。然而,关于斑马鱼心脏衰老的进展和调控,我们的了解还很有限。在这项研究中,我们首先验证了一组与衰老相关的标志物的有效性,并揭示了它们的时空特异性。使用这些标志物,我们发现斑马鱼的心脏衰老始于 24 月龄左右的中年,随后逐渐进展,表现为 DNA 损伤增加、炎症反应和线粒体功能降低。此外,我们还表明,斑马鱼心脏与大鼠心脏的衰老相关表达谱变化相似。总的来说,我们的研究结果为斑马鱼的心脏衰老过程提供了更深入的了解,为开发适合大规模筛选药物靶点的新型心脏衰老模型奠定了基础。

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