当前位置: X-MOL 学术npj Aging Mech. Dis. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A parthenogenetic quasi-program causes teratoma-like tumors during aging in wild-type C. elegans
npj Aging and Mechanisms of Disease Pub Date : 2018-06-13 , DOI: 10.1038/s41514-018-0025-3
Hongyuan Wang 1, 2 , Yuan Zhao 2 , Marina Ezcurra 2, 3 , Alexandre Benedetto 2, 4 , Ann F Gilliat 2 , Josephine Hellberg 2 , Ziyu Ren 2 , Evgeniy R Galimov 2 , Trin Athigapanich 2 , Johannes Girstmair 5 , Maximilian J Telford 5 , Colin T Dolphin 6 , Zhizhou Zhang 1 , David Gems 2
Affiliation  

A long-standing belief is that aging (senescence) is the result of stochastic damage accumulation. Alternatively, senescent pathology may also result from late-life, wild-type gene action (i.e., antagonistic pleiotropy, as argued by Williams) leading to non-adaptive run-on of developmental programs (or quasi-programs) (as suggested more recently by Blagosklonny). In this study, we use existing and new data to show how uterine tumors, a prominent form of senescent pathology in the nematode Caenorhabditis elegans, likely result from quasi-programs. Such tumors develop from unfertilized oocytes which enter the uterus and become hypertrophic and replete with endoreduplicated chromatin masses. Tumor formation begins with ovulation of unfertilized oocytes immediately after exhaustion of sperm stocks. We show that the timing of this transition between program and quasi-program (i.e., the onset of senescence), and the onset of tumor formation, depends upon the timing of sperm depletion. We identify homology between uterine tumors and mammalian ovarian teratomas, which both develop from oocytes that fail to mature after meiosis I. In teratomas, futile activation of developmental programs leads to the formation of differentiated structures within the tumor. We report that older uterine tumors express markers of later embryogenesis, consistent with teratoma-like activation of developmental programs. We also present evidence of coupling of distal gonad atrophy to oocyte hypertrophy. This study shows how the Williams Blagosklonny model can provide a mechanistic explanation of this component of C. elegans aging. It also suggests etiological similarity between teratoma and some forms of senescent pathology, insofar as both are caused by quasi-programs.



中文翻译:

孤雌生殖准程序在野生型线虫衰老过程中导致畸胎瘤样肿瘤

长期以来的一个观点是,衰老(衰老)是随机损伤累积的结果。或者,衰老病理学也可能是由于生命晚期的野生型基因作用(即拮抗性多效性,如威廉姆斯所主张的)导致发育程序(或准程序)的非适应性延续(如最近提出的)由布拉戈斯克伦尼)。在这项研究中,我们使用现有的和新的数据来展示子宫肿瘤(线虫秀丽隐杆线虫衰老病理学的一种重要形式)如何可能是由准程序引起的。这种肿瘤由未受精的卵母细胞发展而来,卵母细胞进入子宫并变得肥大并充满内复制的染色质团块。肿瘤的形成始于精子储备耗尽后未受精卵母细胞立即排卵。我们表明,程序和准程序之间的转变(即衰老的开始)以及肿瘤形成的开始取决于精子耗竭的时间。我们确定了子宫肿瘤和哺乳动物卵巢畸胎瘤之间的同源性,这两种畸胎瘤都是由减数分裂一后未能成熟的卵母细胞发育而来。在畸胎瘤中,发育程序的无效激活导致肿瘤内形成分化结构。我们报告说,较老的子宫肿瘤表达晚期胚胎发生的标志物,与发育程序的畸胎瘤样激活一致。我们还提供了远端性腺萎缩与卵母细胞肥大耦合的证据。这项研究展示了 Williams Blagosklonny 模型如何为秀丽隐杆线虫衰老的这一组成部分提供机械解释。它还表明畸胎瘤和某些形式的衰老病理学之间的病因学相似性,因为两者都是由准程序引起的。

更新日期:2018-06-13
down
wechat
bug