A transcription elongation factor that links signals from the reproductive system to lifespan extension in Caenorhabditis elegans.
A transcription elongation factor that links signals from the reproductive system to lifespan extension in Caenorhabditis elegans.
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DOI：
10.1371/journal.pgen.1000639
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发表时间：
2009-09
期刊：
影响因子：
4.5
通讯作者：
Kenyon C
中科院分区：
文献类型：
--
作者：
Ghazi A;Henis-Korenblit S;Kenyon C
在秀丽隐杆线虫和黑腹果蝇中，索马体的衰老受到生殖细胞的影响。当生殖干细胞被移除时，衰老减缓，寿命延长。体细胞组织对生殖细胞丧失的反应机制还不清楚。令人惊讶的是，我们发现一个预测的转录延伸因子，TCER-1，在这一过程中起着关键作用。TCER-1是生殖细胞丢失所必需的，以增加C。线虫的寿命，它作为一个调节开关的途径。当生殖细胞被去除时，体细胞组织中的TCER-1水平升高。这种增加足以触发关键的下游事件，因为tcer-1的过表达延长了具有完整生殖系统的正常动物的寿命。我们的研究结果表明，TCER-1通过促进由保守的、延长寿命的转录因子fos-16/FOXO调节的一组基因的表达来延长寿命。有趣的是，TCER-1并不需要TCER-16/FOXO来延长胰岛素/IGF-1信号转导减少的动物的寿命。因此，TCER-1特异性地将广泛使用的转录因子α-16/FOXO的活性与生殖组织的长寿信号联系起来。动物的生殖状况和寿命密切相关。年龄的增长会影响大多数动物的繁殖能力。然而，人们对生殖状态如何影响寿命知之甚少。对蠕虫和苍蝇的实验表明，去除产生配子的细胞，即“生殖细胞”，可以使它们活得更长。我们对参与这一过程的基因和分子知之甚少。在这项研究中，我们已经确定了一个名为tcer-1的基因，当其生殖细胞被去除时，该基因可以促进线虫的寿命。基因tcer-1编码一种蛋白质TCER-1，该蛋白质被预测作为"转录延伸因子"发挥作用（它允许在基因表达过程中完成RNA合成）。我们的实验表明，当蠕虫的生殖细胞被去除时，TCER-1与一种名为TCER-16/FOXO的转录因子合作，表达有助于延长寿命的基因。除了生殖细胞的损失外，E16/FOXO还可以延长寿命，以响应其他生理线索。然而，TCER-1特异性地帮助这种广泛使用的长寿蛋白对反映生殖状态的信号做出反应。已知TCER-16/FOXO的对应物控制包括人类在内的其他生物体的衰老，因此TCER-1的鉴定可能会更好地了解其他物种的生殖和衰老之间的关系。
In Caenorhabditis elegans and Drosophila melanogaster, the aging of the soma is influenced by the germline. When germline-stem cells are removed, aging slows and lifespan is increased. The mechanism by which somatic tissues respond to loss of the germline is not well-understood. Surprisingly, we have found that a predicted transcription elongation factor, TCER-1, plays a key role in this process. TCER-1 is required for loss of the germ cells to increase C. elegans' lifespan, and it acts as a regulatory switch in the pathway. When the germ cells are removed, the levels of TCER-1 rise in somatic tissues. This increase is sufficient to trigger key downstream events, as overexpression of tcer-1 extends the lifespan of normal animals that have an intact reproductive system. Our findings suggest that TCER-1 extends lifespan by promoting the expression of a set of genes regulated by the conserved, life-extending transcription factor DAF-16/FOXO. Interestingly, TCER-1 is not required for DAF-16/FOXO to extend lifespan in animals with reduced insulin/IGF-1 signaling. Thus, TCER-1 specifically links the activity of a broadly deployed transcription factor, DAF-16/FOXO, to longevity signals from reproductive tissues. The reproductive status and longevity of animals are strongly interlinked. Increasing age influences the reproductive capacities of most animals. However, little is known about how reproductive status might affect lifespan. Experiments in worms and flies have shown that removing cells that give rise to gametes, the “germ cells”, makes them live longer. We know very little about the genes and molecules that are involved in this process. In this study, we have identified a gene called tcer-1 that promotes the longevity of the roundworm Caenorhabditis elegans when its germ cells are removed. The gene tcer-1 codes for a protein, TCER-1, that is predicted to function as a “transcription elongation factor” (it allows the completion of RNA synthesis during the process of gene expression). Our experiments imply that when the germ cells of worms are removed, TCER-1 collaborates with a transcription factor called DAF-16/FOXO to express genes that contribute to increased longevity. DAF-16/FOXO can extend lifespan in response to other physiological cues besides loss of germ cells. However, TCER-1 specifically helps this widely used longevity protein to respond to signals that reflect the reproductive status. Counterparts of DAF-16/FOXO are known to control aging in other organisms, including humans, so the identification of TCER-1 may lead to a better understanding of the relationship between reproduction and aging in other species, too.
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影响因子：
11.8
作者：
Gerisch, B;Weitzel, C;Antebi, A
通讯作者：
Antebi, A
DOI：
10.1073/pnas.041566798
发表时间：
2001-02-13
影响因子：
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作者：
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DOI：
10.1073/pnas.160266597
发表时间：
2000-08-01
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
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