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A soma-to-germline transformation in long-lived Caenorhabditis elegans mutants

机译:长寿命秀丽隐杆线虫突变体的体细胞到种系转化

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摘要

Unlike the soma, which ages during the lifespan of multicellular organisms, the germ line traces an essentially immortal lineage. Genomic instability in somatic cells increases with age, and this decline in somatic maintenance might be regulated to facilitate resource reallocation towards reproduction at the expense of cellular senescence. Here we show that Caenorhabditis elegans mutants with increased longevity exhibit a soma-to-germline transformation of gene expression programs normally limited to the germ line. Decreased insulin-like signalling causes the somatic misexpression of the germline-limited pie-1 and pgl family of genes in intestinal and ectodermal tissues. The forkhead boxO1A (FOXO) transcription factor DAF-16, the major transcriptional effector of insulin-like signalling, regulates pie-1 expression by directly binding to the pie-1 promoter. The somatic tissues of insulin-like mutants are more germline-like and protected from genotoxic stress. Gene inactivation of components of the cytosolic chaperonin complex that induce increased longevity also causes somatic misexpression of PGL-1. These results indicate that the acquisition of germline characteristics by the somatic cells of C. elegans mutants with increased longevity contributes to their increased health and survival.
机译:与在多细胞生物体的生命周期中衰老的体细胞不同,种系具有基本永生的谱系。体细胞中的基因组不稳定性会随着年龄的增长而增加,因此可以调节体细胞维持率的下降,以促进资源的重新分配,从而以细胞衰老为代价。在这里,我们显示寿命延长的秀丽隐杆线虫突变体表现出从基因到生殖细胞的基因表达程序转化,通常限于种系。胰岛素样信号转导的减少会导致肠道和外胚层组织中种系受限的pie-1和pgl家族基因发生体细胞错误表达。叉头盒O1A(FOXO)转录因子DAF-16是胰岛素样信号的主要转录效应子,它通过直接结合pie-1启动子来调节pie-1的表达。胰岛素样突变体的体细胞组织更像种系,并免受遗传毒性胁迫。导致寿命延长的胞质伴侣蛋白复合物成分的基因失活也会引起PGL-1的体细胞错误表达。这些结果表明,寿命延长的秀丽线虫突变体的体细胞获得种系特征有助于它们的健康和存活。

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  • 来源
    《Nature》 |2009年第25期|1079-10841161|共7页
  • 作者单位

    Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA.;

    Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA.;

    Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA.;

    Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA.;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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