Cellular ageing is a systematic process affecting the entirety of cell structure and function. Since changes in gene expression are extensive and global during ageing, involvement of general transcription regulators in the phenomenon is likely. Here, we focus on NF-Y, the major CCAAT box-binding factor, which exerts differential regulation on a wide variety of genes through its interaction with the CCAAT box present in as many as 25% of the eukaryotic genes. When a cell ages, senescing signals arise, typically through DNA damage due to oxidative stress or telomere shortening, and are transduced to proteins such as p53, retinoblastoma protein, and phosphatidylinositol 3-kinase. Among them, activated p53 family proteins suppress the function of NF-Y and thereby downregulate a set of cell cycle-related genes, including E2F1, which further leads to downregulation of E2F-regulated genes and cell cycle arrest. The p53 family also induces other ageing phenotypes such as morphological alterations and senescence-associated beta-galactosidase (SA-gal) presumably by upregulation of some genes through NF-Y suppression. In fact, the activities of NF-Y and E2F decrease during ageing and a dominant negative NF-YA induces SA-gal. Based on these observations, NF-Y appears to play an important role in the process of cellular ageing.

中文翻译：

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CCAAT盒结合因子CBF / NF-Y对细胞衰老的转录调控。

细胞衰老是影响整个细胞结构和功能的系统过程。由于基因表达的变化在衰老过程中是广泛而全面的，因此一般转录调节因子可能参与该现象。在这里，我们关注主要的CCAAT盒结合因子NF-Y，它通过与多达25％的真核基因中存在的CCAAT盒相互作用而对多种基因施加差异调节。当细胞衰老时，通常通过由于氧化应激或端粒缩短引起的DNA损伤而产生感觉信号，并被转导到诸如p53，视网膜母细胞瘤蛋白和磷脂酰肌醇3激酶之类的蛋白上。其中，活化的p53家族蛋白抑制NF-Y的功能，从而下调一组与细胞周期相关的基因，包括E2F1，这进一步导致E2F调控的基因下调和细胞周期停滞。p53家族还诱导其他衰老表型，例如形态改变和与衰老相关的β-半乳糖苷酶（SA-gal），可能是由于通过抑制NF-Y抑制了某些基因的表达。实际上，衰老过程中NF-Y和E2F的活性下降，显性负性NF-YA诱导SA-gal。基于这些观察，NF-Y似乎在细胞衰老过程中起重要作用。衰老过程中NF-Y和E2F的活性下降，显性负性NF-YA诱导SA-gal。基于这些观察，NF-Y似乎在细胞衰老过程中起重要作用。衰老过程中NF-Y和E2F的活性下降，显性负性NF-YA诱导SA-gal。基于这些观察，NF-Y似乎在细胞衰老过程中起重要作用。