cep-1/p53-dependent dysplastic pathology of the aging C. elegans gonad.
cep-1/p53-dependent dysplastic pathology of the aging C. elegans gonad.
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DOI：
10.18632/aging.100448
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Melov S
中科院分区：
文献类型：
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作者：
McGee MD;Day N;Graham J;Melov S
梭线虫的生殖系和体细胞性腺一直活跃地发育，直到动物成年，然后随着动物年龄的增长继续经历惊人的变化。报道的变化包括可用精子的耗尽，直到中年卵母细胞质量下降，生殖细胞核减少，生育能力下降，以及衰老C的中间体DNA积累。优雅的在这里，我们集中在老龄动物的性腺老化，并详细显示，老化的性腺经历了一个巨大的子宫增长组成的核内复制的卵母细胞，蛋黄，和染色质的扩张。我们使用了一系列新的成像技术结合组织学方法重建老年蠕虫的三维，并显示在老年动物子宫内肿胀的肿块，占据了蠕虫的大部分直径。我们将这种加速生长与cep-1/p53肿瘤抑制因子联系起来。由于cep-1是DNA损伤诱导细胞凋亡所必需的，而daf-2限制了寿命，这些结果表明年龄相关的DNA损伤在子宫发育不良中的作用，在某些方面类似于衰老哺乳动物中可能发生的癌前病变。
The C. elegans germline and somatic gonad are actively developing until the animal reaches adulthood, and then continue to undergo striking changes as the animal ages. Reported changes include a depletion of available sperm, a decrease in oocyte quality up till mid-life, a reduction in germline nuclei, a decrease in fertility, and an accumulation of DNA in the midbody of aging C. elegans. Here, we have focused on the aging gonad in old animals, and show in detail that the aging gonad undergoes a massive uterine growth composed of endoreduplicating oocytes, yolk, and expanses of chromatin. We use a novel series of imaging techniques in combination with histological methodology for reconstructing aged worms in 3-dimensions, and show in old animals growing masses swelling inside the uterus to occupy most of the diameter of the worm. We link this accelerated growth to the cep-1/p53 tumor suppressor. Because cep-1 is required for DNA damage induced apoptosis, and daf-2 limits longevity, these results suggest a role for age-related DNA damage in dysplastic uterine growths, which in some respects resemble premalignant changes that can occur in aging mammals.