Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
Nucleus. 2011 Nov-Dec;2(6):549-55. doi: 10.4161/nucl.2.6.17986. Epub 2011 Nov 1.
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.
在过去的几年中，microRNAs（miRNAs）的发现彻底改变了基因表达调控的经典概念，并引入了一类新的分子，它们可能有助于解释衰老过程中观察到的复杂变化。尽管已经证明几种秀丽隐杆线虫 miRNAs 会影响线虫的寿命，但目前关于 miRNA 介导的哺乳动物衰老调控的知识仍然有限。最近，我们使用 Zmpste24-/- 小鼠（一种模拟亨廷顿氏舞蹈症的鼠模型）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 miRNAs 的表达水平，包括 miR-1 和 miR-29 的显著上调。此外，我们发现这些 miRNA 的异常表达可能通过调节生长激素轴和 DNA 损伤反应途径的关键成分水平，导致突变小鼠出现早衰表型。在这里，我们讨论了这些最新发现，并总结了目前关于与衰老相关的 miRNAs 或 geromiRs 参与衰老和长寿调控的证据。
