Uncoupling of longevity and telomere length in C. elegans.

Uncoupling of longevity and telomere length in C. elegans.
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秀丽隐杆线虫中长寿和端粒长度的解偶联。

DOI:
10.1371/journal.pgen.0010030
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发表时间:
2005-09
期刊:
影响因子:
4.5
通讯作者:
Karlseder, J
Karlseder, J
中科院分区:
生物学2区
文献类型:
--
作者:
Raices, M;Maruyama, H;Dillin, A;Karlseder, J

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线虫秀丽隐杆线虫在完成其发育阶段和短暂的生殖期后,作为完全由有丝分裂后细胞组成的生物体度过其成年生活的剩余部分。在这里,我们表明,端粒长度变化很大,在克隆种群的野生型蠕虫,这些长度的差异是保守的至少十代,这表明顺式长度调节机制。这一观察结果得到了加强,发现在不同的蠕虫菌株的体积端粒长度有很大的差异。尽管哺乳动物细胞中端粒长度和克隆细胞衰老密切相关,但端粒长的线虫既不长寿,端粒短的蠕虫种群也不表现出较短的寿命。相反,长寿的daf-2和短命的daf-16突变动物可以有长或短的端粒。有丝分裂后细胞的端粒长度在衰老过程中没有变化,动物对应激的反应与端粒长度无关。总的来说,我们的数据表明,端粒长度和寿命可以在有丝分裂后的环境中解偶联,这表明复制依赖性和非依赖性衰老的不同途径。秀丽隐杆线虫(Caesophylhabditis elegans)历来被用作研究生物衰老的有力模型。经过短暂的繁殖期,成虫由959个有丝分裂后的细胞组成。端粒是线性染色体的自然末端,长期以来一直与有丝分裂细胞的衰老过程有关,端粒缩短被认为是细胞分裂的限制因素。作者发现C.线虫的染色体不受生物体衰老的影响。蠕虫端粒的特点是详细的,并发现在个别克隆差异很大。这些差异在几个种群中是保守的,表明蠕虫和哺乳动物的端粒长度受到类似机制的控制,强调了C。作为端粒生物学的模型。然而,还没有发现端粒长度决定动物的潜在寿命,因为端粒短的蠕虫和端粒长的蠕虫活得一样长。反之亦然,由于胰岛素受体途径突变而改变寿命的蠕虫在端粒长度上没有任何变化。端粒长度也被发现是恒定的,在孤立的,老化的蠕虫种群,这表明,生物体老化可以从有丝分裂老化解耦。
The nematode Caenorhabditis elegans, after completing its developmental stages and a brief reproductive period, spends the remainder of its adult life as an organism consisting exclusively of post-mitotic cells. Here we show that telomere length varies considerably in clonal populations of wild-type worms, and that these length differences are conserved over at least ten generations, suggesting a length regulation mechanism in cis. This observation is strengthened by the finding that the bulk telomere length in different worm strains varies considerably. Despite the close correlation of telomere length and clonal cellular senescence in mammalian cells, nematodes with long telomeres were neither long lived, nor did worm populations with comparably short telomeres exhibit a shorter life span. Conversely, long-lived daf-2 and short-lived daf-16 mutant animals can have either long or short telomeres. Telomere length of post-mitotic cells did not change during the aging process, and the response of animals to stress was found independent of telomere length. Collectively, our data indicate that telomere length and life span can be uncoupled in a post-mitotic setting, suggesting separate pathways for replication-dependent and -independent aging. The worm Caenorhabditis elegans has historically been used as a powerful model to study organismal aging. After a brief reproductive period, an adult worm consists of 959 post-mitotic cells. Telomeres, the natural ends of linear chromosomes, have long been implicated in the aging process of mitotic cells, and telomere shortening has been proposed to be a limiting factor in cell division. The authors show that telomere length of C. elegans chromosomes is independent of organismal aging. Worm telomeres were characterized in detail, and found to vary considerably in individual clones. These differences were conserved over several populations, suggesting that telomere length is controlled by similar mechanisms in worms and mammals, emphasizing the value of C. elegans as a model for telomere biology. However, telomere length has not been found to determine the potential life span of the animals, since worms with short telomeres lived as long as worms with long telomeres. Vice versa, worms that have an altered life span due to mutations in the insulin receptor pathway do not show any changes in telomere length. Telomere length was also found to be constant in isolated, aging worm populations, suggesting that organismal aging can be uncoupled from mitotic aging.
DOI: 10.1093/nar/gkh661
发表时间: 2004-06-01
影响因子: 14.9
作者:
Cheung, I;Schertzer, M;Baird, DM
通讯作者: Baird, DM
DOI: 10.1073/pnas.97.10.5285
发表时间: 2000-05-09
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DOI: 10.1126/science.1077780
发表时间: 2002-12-20
期刊: SCIENCE
影响因子: 56.9
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期刊: CELL
影响因子: 64.5
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通讯作者: Kenyon, C
DOI: 10.1126/science.279.5349.349
发表时间: 1998-01-16
期刊: SCIENCE
影响因子: 56.9
作者:
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