Circulating microRNA signature of genotype-by-age interactions in the long-lived Ames dwarf mouse.
Circulating microRNA signature of genotype-by-age interactions in the long-lived Ames dwarf mouse.
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DOI：
10.1111/acel.12373
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发表时间：
2015-12
期刊：
影响因子：
7.8
通讯作者：
Masternak MM
中科院分区：
文献类型：
--
作者：
Victoria B;Dhahbi JM;Nunez Lopez YO;Spinel L;Atamna H;Spindler SR;Masternak MM
最近的证据表明，血清中特异性miRNAs的水平随年龄而显著变化。循环sncRNA作为信号分子和调节广谱细胞功能的能力暗示它们是衰老过程中的关键参与者。为了发现影响长寿艾姆斯侏儒小鼠衰老的循环sncRNA，我们对从年轻和老年小鼠血清中提取的小RNA进行了深度测序。我们的分析显示了衰老过程中21种miRNA循环水平的基因型特异性变化[基因型与年龄相互作用（GbA）]。基因型-年龄miRNAs显示出四种不同的表达模式和参与年龄相关过程的转录物的显著过度靶向。对推定和验证的miRNA靶点的功能富集分析突出了细胞过程，例如肿瘤抑制、抗炎反应以及Wnt、胰岛素、mTOR和MAPK信号通路的调节等。对艾姆斯小鼠中循环GbA miRNA与另一种长寿小鼠中通过热量限制（CR）调节的循环miRNA的比较分析表明，CR样和CR非依赖性机制有助于艾姆斯小鼠的长寿。总之，我们首次在长寿的艾姆斯小鼠中发现了受年龄调节的循环miRNA的特征。
Recent evidence demonstrates that serum levels of specific miRNAs significantly change with age. The ability of circulating sncRNAs to act as signaling molecules and regulate a broad spectrum of cellular functions implicates them as key players in the aging process. To discover circulating sncRNAs that impact aging in the long‐lived Ames dwarf mice, we conducted deep sequencing of small RNAs extracted from serum of young and old mice. Our analysis showed genotype‐specific changes in the circulating levels of 21 miRNAs during aging [genotype‐by‐age interaction (GbA)]. Genotype‐by‐age miRNAs showed four distinct expression patterns and significant overtargeting of transcripts involved in age‐related processes. Functional enrichment analysis of putative and validated miRNA targets highlighted cellular processes such as tumor suppression, anti‐inflammatory response, and modulation of Wnt, insulin, mTOR, and MAPK signaling pathways, among others. The comparative analysis of circulating GbA miRNAs in Ames mice with circulating miRNAs modulated by calorie restriction (CR) in another long‐lived mouse suggests CR‐like and CR‐independent mechanisms contributing to longevity in the Ames mouse. In conclusion, we showed for the first time a signature of circulating miRNAs modulated by age in the long‐lived Ames mouse.