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首页> 外文期刊>Cell motility and the cytoskeleton >Gliotoxin reverses age-dependent nuclear morphology phenotypes, ameliorates motility, but fails to affect lifespan of adult Caenorhabditis elegans.
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Gliotoxin reverses age-dependent nuclear morphology phenotypes, ameliorates motility, but fails to affect lifespan of adult Caenorhabditis elegans.

机译：胶质毒素逆转了年龄依赖性的核形态表型，改善了运动能力，但没有影响成年秀丽隐杆线虫的寿命。

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摘要

Specific mutations in human LMNA or loss of ZMPSTE26 activity cause abnormal processing of lamin A and early aging diseases, including Hutchinson Gilford progeria syndrome (HGPS). HGPS fibroblasts in culture undergo age-dependent progressive changes in nuclear architecture. Treating these cells with farnesyl transferase inhibitors (FTIs) reverse these nuclear phenotypes and also extend lifespan of mice HGPS models. Dermal cells derived from healthy old humans also accumulate the abnormally processed lamin A. However, the effect of FTIs on normal aging cells was not tested. Aging adult C. elegans cells show changes in nuclear architecture similar to HGPS fibroblasts and down regulating lamin expression in adult C. elegans reduces their lifespan. Here, we show that nuclei of adult C. elegans, in which lamin is down-regulated, have similar phenotypes to normal aging nuclei, but at an earlier age. We further show that treating adult C. elegans with the FTI gliotoxin reverses nuclear phenotypes and improves motility of aging worms. However, the average lifespan of the gliotoxin-treated animals was similar to that of untreated animals. These results suggest that lamins are involved in the process of normal aging in C. elegans.
机译：人LMNA的特定突变或ZMPSTE26活性的丧失会导致层粘连蛋白A的异常加工和早期衰老疾病，包括Hutchinson Gilford早衰综合征（HGPS）。文化中的HGPS成纤维细胞在核结构中经历了年龄依赖性的渐进式变化。用法呢基转移酶抑制剂（FTI）处理这些细胞可逆转这些核表型，也可延长小鼠HGPS模型的寿命。源自健康老年人的皮肤细胞也会积聚异常加工的层粘连蛋白A。但是，未测试FTI对正常衰老细胞的作用。成年的秀丽隐杆线虫细胞显示出类似于HGPS成纤维细胞的核结构变化，成年秀丽的秀丽隐杆线虫中下层蛋白表达的下调缩短了它们的寿命。在这里，我们显示成年线虫的核，其中核纤层蛋白被下调，具有与正常衰老核类似的表型，但年龄较早。我们进一步表明，用FTI gliotoxin处理成人秀丽隐杆线虫可逆转核表型，并改善衰老蠕虫的运动能力。然而，用角蛋白毒素处理的动物的平均寿命与未处理动物的平均寿命相似。这些结果表明，线粒体参与秀丽隐杆线虫的正常衰老过程。

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