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Micromanaging aging with miRNAs

机译：使用miRNA进行老化的微管理

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Over the last years, the discovery of microRNAs (miRNAs) has revolutionized the classic concepts of gene expression regulation and has introduced a new group of molecules that may contribute to the complex changes observed during aging. Although several Caenorhabditis elegans miRNAs have been proved to influence the nematode life span, the current knowledge about miRNA-mediated regulation of mammalian aging is still limited. Recently, we have analyzed the functional relevance of miRNAs in accelerate aging by using Zmpste24~(-/) ~(-) mice, a murine model that phenocopies Hutchinson-Gilford progeria syndrome. These studies have revealed that the nuclear abnormalities present in these mice affect the expression levels of several miRNAs, including a marked upregulation of miR-1 and miR-29. Furthermore, we have found that the altered expression of these miRNAs may contribute to the progeroid phenotype of mutant mice by modulating the levels of key components of the somatroph axis and DNA damage response pathways. Here, we discuss these recent discoveries and summarize the present evidences regarding the involvement of aging-associated miRNAs or geromiRs in senescence and longevity regulation.
机译：在过去的几年中，microRNA（miRNA）的发现彻底改变了基因表达调控的经典概念，并引入了一组新的分子，这些分子可能会导致衰老过程中观察到的复杂变化。尽管已经证明了几种秀丽隐杆线虫miRNA会影响线虫的寿命，但是关于miRNA介导的哺乳动物衰老调节的当前知识仍然有限。最近，我们通过使用Zmpste24〜（-/）〜（-）小鼠（一种表型为Hutchinson-Gilford早衰综合征的小鼠模型）分析了miRNA在加速衰老中的功能相关性。这些研究表明，这些小鼠中存在的核异常会影响几种miRNA的表达水平，包括miR-1和miR-29的明显上调。此外，我们发现这些miRNA的表达改变可能通过调节体细胞轴的关键成分和DNA损伤反应途径的水平而有助于突变小鼠的胚状表型。在这里，我们讨论这些最新发现，并总结有关衰老相关的miRNA或geromiRs参与衰老和长寿调节的当前证据。

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