Laboratory of Molecular Biology and Immunology, NIA-IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224, USA.
Trends Genet. 2011 Jun;27(6):233-41. doi: 10.1016/j.tig.2011.03.005. Epub 2011 May 16.
Cellular senescence was first reported five decades ago as a state of long-term growth inhibition in viable, metabolically active cells cultured in vitro. However, evidence that senescence occurs in vivo and underlies pathophysiologic processes has only emerged over the past few years. Coincident with this increased knowledge, understanding of the mechanisms that control senescent-cell gene expression programs has also recently escalated. Such mechanisms include a prominent group of regulatory factors (miRNA), a family of small, noncoding RNAs that interact with select target mRNAs and typically repress their expression. Here, we review recent reports that miRNAs are key modulators of cellular senescence, and we examine their influence upon specific senescence-regulatory proteins. We discuss evidence that dysregulation of miRNA-governed senescence programs underlies age-associated diseases, including cancer.
细胞衰老最初是在五十年前被报道的,指的是在体外培养的存活、代谢活跃的细胞中出现的长期生长抑制状态。然而,近年来才出现衰老发生在体内并构成病理生理过程基础的证据。随着这方面知识的增加,控制衰老细胞基因表达程序的机制也得到了最近的深入研究。这类机制包括一组重要的调节因子(miRNA),miRNA 是一类小的非编码 RNA,与特定的靶 mRNA 相互作用,通常抑制其表达。在这里,我们回顾了最近关于 miRNA 是细胞衰老的关键调节因子的报告,并研究了它们对特定衰老调节蛋白的影响。我们讨论了 miRNA 调控的衰老程序失调是如何导致与年龄相关的疾病(包括癌症)的证据。