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年龄相关的斑马鱼和大鼠转录组差异分析:对脊椎动物衰老多样性的深入了解。

Age-Associated Different Transcriptome Profiling in Zebrafish and Rats: an Insight into the Diversity of Vertebrate Aging.

机构信息

Department of Aquatic Bioscience, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo, Tokyo, 113-8657, Japan.

School of Biomedical Engineering, Faculty of Applied Science and Faculty of Medicine, The University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.

出版信息

Mar Biotechnol (NY). 2022 Oct;24(5):895-910. doi: 10.1007/s10126-022-10153-9. Epub 2022 Sep 5.

Abstract

Most mammals, including humans, show obvious aging phenotypes, for example, loss of tissue plasticity and sarcopenia. In this regard, fish can be attractive models to study senescence because of their unique aging characteristics. The lifespan of fish varies widely, and several species can live for over 200 years. Moreover, some fish show anti-aging features and indeterminate growth throughout their life. Therefore, exploring the aging mechanism in fish could provide new insights into vertebrate aging. To this end, we conducted RNA sequencing (RNA-seq) assays for various organs and growth stages of zebrafish and compared the data with previously published RNA-seq data of rats. Age-associated differentially expressed genes (DEGs) for all zebrafish tissue samples reveal the upregulation of circadian genes and downregulation of hmgb3a. On one hand, a comparative analysis of DEG profiles associated with aging between zebrafish and rats identifies upregulation of circadian genes and downregulation of collagen genes as conserved transcriptome changes. On the other hand, in zebrafish, upregulation of autophagy-related genes in muscles and AP-1 transcription factor genes in various tissues is observed, which may imply fish-specific anti-aging characteristics. Consistent with our knowledge of mammalian aging, DEG profiles related to tissue senescence are observed in rats. We also detect age-associated downregulation of muscle homeostasis and differentiation-related genes in zebrafish gills, indicating a fish-specific senescence phenotype. Our results indicate both common and different aging profiles between fish and mammals, which could be used for future translational research.

摘要

大多数哺乳动物,包括人类,都表现出明显的衰老表型,例如组织可塑性丧失和肌肉减少症。在这方面,鱼类由于其独特的衰老特征,可以成为研究衰老的有吸引力的模型。鱼类的寿命差异很大,有几种鱼类可以活 200 年以上。此外,一些鱼类在其一生中表现出抗老化特征和不定向生长。因此,探索鱼类的衰老机制可以为脊椎动物衰老提供新的见解。为此,我们对斑马鱼的各种器官和生长阶段进行了 RNA 测序(RNA-seq)分析,并将数据与之前发表的大鼠 RNA-seq 数据进行了比较。所有斑马鱼组织样本的与年龄相关的差异表达基因(DEG)显示,昼夜节律基因上调,hmgb3a 下调。一方面,对斑马鱼和大鼠之间与衰老相关的 DEG 图谱进行比较分析,确定昼夜节律基因上调和胶原蛋白基因下调为保守的转录组变化。另一方面,在斑马鱼中,肌肉中自噬相关基因上调和各种组织中 AP-1 转录因子基因上调,这可能暗示着鱼类特有的抗老化特征。与我们对哺乳动物衰老的认识一致,在大鼠中观察到与组织衰老相关的 DEG 图谱。我们还检测到斑马鱼鳃中与肌肉稳态和分化相关的基因随年龄下降,表明存在鱼类特有的衰老表型。我们的研究结果表明鱼类和哺乳动物之间存在共同和不同的衰老特征,可以用于未来的转化研究。

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