New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen.
New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen.
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DOI：
10.1371/journal.pgen.0010017
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发表时间：
2005-07
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：
Hansen M;Hsu AL;Dillin A;Kenyon C
我们对衰老调控的大部分知识来自于最初为其他表型分离的突变体。为了询问我们目前对衰老的看法是否受到选择偏差的影响，并加深我们对已知长寿途径的理解，我们筛选了一个基因组秀丽隐杆线虫RNAi文库，以寻找延长寿命的克隆。我们确定了23个影响信号转导、应激反应、基因表达和代谢的新的长寿基因，并将这些基因分配给特定的长寿途径。我们最重要的发现是：（i）饮食限制延长了C。通过下调关键基因的表达，包括许多大分子甲基化所需的基因，（ii）整联蛋白信号传导可能在寿命调节中发挥一般的，进化上保守的作用，以及（iii）特定的亲脂性激素可能以β-16/FOXO依赖的方式影响寿命。令人惊讶的是，在具有保守序列结构域的新基因中，只有一个与已知的长寿途径无关。因此，我们目前对衰老遗传学的看法可能并没有被选择偏见严重扭曲。寿命在C。秀丽线虫受到几种遗传途径和过程的影响;关于这种衰老调节的大量信息来自最初由于其他表型而鉴定的遗传突变体。因此，为了询问当前关于衰老遗传学的观点是否受到选择偏差的显著影响，并加深对已知长寿途径的理解，汉森等人筛选了一个全基因组RNAi文库，以寻找在喂食线虫时延长寿命的细菌克隆。 研究人员确定了23个影响信号转导、应激反应、基因表达和代谢的新长寿基因，并将这些基因分配给特定的长寿途径。他们最重要的发现是：（i）饮食限制延长了C。通过下调关键基因的表达，包括许多大分子甲基化所需的基因，（ii）整联蛋白信号传导可能在寿命调节中发挥一般的、进化上保守的作用，以及（iii）特定的亲脂性激素可能通过保守的胰岛素/IGF-1信号传导途径影响寿命。令人惊讶的是，作者发现，在具有保守序列结构域的新基因中，只有一个与已知的长寿途径无关。因此，目前关于衰老遗传学的观点可能并没有被选择偏见严重扭曲。作者希望对这些基因的进一步研究能为衰老机制提供有价值的信息，不仅在C。也存在于高等生物中。
Most of our knowledge about the regulation of aging comes from mutants originally isolated for other phenotypes. To ask whether our current view of aging has been affected by selection bias, and to deepen our understanding of known longevity pathways, we screened a genomic Caenorhabditis elegans RNAi library for clones that extend lifespan. We identified 23 new longevity genes affecting signal transduction, the stress response, gene expression, and metabolism and assigned these genes to specific longevity pathways. Our most important findings are (i) that dietary restriction extends C. elegans' lifespan by down-regulating expression of key genes, including a gene required for methylation of many macromolecules, (ii) that integrin signaling is likely to play a general, evolutionarily conserved role in lifespan regulation, and (iii) that specific lipophilic hormones may influence lifespan in a DAF-16/FOXO-dependent fashion. Surprisingly, of the new genes that have conserved sequence domains, only one could not be associated with a known longevity pathway. Thus, our current view of the genetics of aging has probably not been distorted substantially by selection bias. Lifespan in C. elegans is influenced by several genetic pathways and processes; a great deal of the information about this regulation of aging comes from genetic mutants originally identified because of other phenotypes. Therefore, to ask whether the current view of the genetics of aging has been significantly affected by selection bias, and to deepen the understanding of known longevity pathways, Hansen et al. screened a genome-wide RNAi library for bacterial clones that extend lifespan when fed to the nematode Caenorhabditis elegans. The investigators identified 23 new longevity genes affecting signal transduction, the stress response, gene expression, and metabolism and assigned these genes to specific longevity pathways. Their most important findings were (i) that dietary restriction extended C. elegans' lifespan by down-regulating expression of key genes, including a gene required for methylation of many macromolecules, (ii) that integrin signaling is likely to play a general, evolutionarily conserved role in lifespan regulation, and (iii) that specific lipophilic hormones may influence lifespan through the conserved insulin/IGF-1 signaling pathway. Surprisingly, the authors found that of the new genes that have conserved sequence domains, only one could not be associated with a known longevity pathway. Thus, the current view of the genetics of aging has probably not been distorted substantially by selection bias. The authors expect the further study of these genes to provide valuable information about the mechanisms of aging, not only in C. elegans but also in higher organisms.
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影响因子：
11.8
作者：
Gerisch, B;Weitzel, C;Antebi, A
通讯作者：
Antebi, A
影响因子：
12.3
作者：
通讯作者：
--
影响因子：
30.8
作者：
Lee, SS;Lee, RYN;Ruvkun, G
通讯作者：
Ruvkun, G
影响因子：
56.9
作者：
Dillin, A;Hsu, AL;Kenyon, C
通讯作者：
Kenyon, C
DOI：
10.1073/pnas.95.22.13091
发表时间：
1998-10-27
影响因子：
11.1
作者：
Lakowski, B;Hekimi, S
通讯作者：
Hekimi, S