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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >Elevated ATF4 Function in Fibroblasts and Liver of Slow-Aging Mutant Mice
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Elevated ATF4 Function in Fibroblasts and Liver of Slow-Aging Mutant Mice

机译:慢老化突变小鼠成纤维细胞和肝脏中ATF4功能的升高

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摘要

Work in yeast has shown that longevity extension induced by nutrient deprivation, altered ribosomal function, or diminished target of rapamycin action requires the activity of GCN4. We hypothesized that increased activity of ATF4, the mammalian equivalent of yeast GCN4, might be characteristic of mutations that extend mouse life span. Fibroblasts from the skin of two such mutants (Snell dwarf and PAPP-A knockout) were found to have higher levels of ATF4 protein and expression of several ATF4 target genes in responses to amino acid withdrawal, cadmium, hydrogen peroxide, and tunicamycin. ATF4 pathways were also elevated in liver of both kinds of long-lived mutant mice. Thus, a connection between ATF4 pathways and longevity may have deep evolutionary roots, and further studies of ATF4 mechanisms may provide insights into the links between cellular stress resistance, protein translation control, and aging.
机译:酵母中的研究表明,营养缺乏,核糖体功能改变或雷帕霉素作用靶点降低引起的寿命延长需要GCN4的活性。我们假设,ATF4(酵母GCN4的哺乳动物等效物)的活性增加可能是延长小鼠寿命的突变的特征。发现来自两个这样的突变体(斯内尔矮人和PAPP-A敲除)的皮肤成纤维细胞具有较高水平的ATF4蛋白,并响应氨基酸戒断,镉,过氧化氢和衣霉素而表达了一些ATF4靶基因。两种长寿突变小鼠的肝脏中ATF4途径也均升高。因此,ATF4途径与寿命之间的联系可能具有深厚的进化根源,并且对ATF4机制的进一步研究可能提供有关细胞抗逆性,蛋白质翻译控制与衰老之间联系的见解。

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