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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：胶毒素逆转依赖年龄依赖的核形态学表型，改善了运动，但没有影响成人Caenorhabdise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或ZMPSTE26活性丧失的特异性突变导致Lamin A和早期衰老疾病的异常加工，包括Hutchinson Gilford Progeria综合征（HGP）。文化的HGPS成纤维细胞经历了年龄依赖性核建筑的逐步变化。用法呢基转移酶抑制剂（FTI）对这些细胞逆转这些核表型，并延长小鼠HGPS模型的寿命。源自健康旧人体的皮肤细胞也积累了异常加工的Lamin A.然而，没有测试FTI对正常老化细胞的影响。老化成人C. Elegans细胞显示与HGPS成纤维细胞相似的核结构的变化，并降低成人C.秀丽隐杆线的调节层压液表达减少了它们的寿命。在这里，我们显示成年人C.杆状杆菌的核，其中Lamin被调节，对正常老化核具有类似的表型，但在较早的年龄。我们进一步表明，随着FTI气毒素治疗成人C.杆骨杆菌，逆转核表型并改善了老化蠕虫的动力。然而，气毒素处理的动物的平均寿命与未处理的动物的平均寿命相似。这些结果表明，Lamins参与了C.秀丽隐杆线虫正常老化的过程。

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