在野生型秀丽隐杆线虫衰老过程中,孤雌生殖准程序引起畸胎瘤样肿瘤。

IF 5.4 Q1 GERIATRICS & GERONTOLOGY
NPJ Aging and Mechanisms of Disease Pub Date : 2018-06-13 eCollection Date: 2018-01-01 DOI:10.1038/s41514-018-0025-3
Hongyuan Wang, Yuan Zhao, Marina Ezcurra, Alexandre Benedetto, Ann F Gilliat, Josephine Hellberg, Ziyu Ren, Evgeniy R Galimov, Trin Athigapanich, Johannes Girstmair, Maximilian J Telford, Colin T Dolphin, Zhizhou Zhang, David Gems
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引用次数: 10

摘要

长期以来,人们一直认为衰老是随机损伤积累的结果。另外,衰老病理也可能是由于晚年野生型基因作用(如Williams所说的拮抗多效性)导致发育程序(或准程序)的非适应性运行(如Blagosklonny最近提出的)。在这项研究中,我们利用现有的和新的数据来显示子宫肿瘤是秀丽隐杆线虫衰老病理的一种突出形式,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,卵母细胞进入子宫后变得肥大并充满了内复制染色质团块。肿瘤的形成始于精子耗尽后未受精的卵母细胞的排卵。我们表明,程序和准程序之间的过渡时间(即衰老的开始)和肿瘤形成的开始,取决于精子消耗的时间。我们发现子宫肿瘤和哺乳动物卵巢畸胎瘤的同源性,它们都是由卵母细胞在减数分裂后未能成熟而发展而来的。在畸胎瘤中,无用的发育程序激活导致肿瘤内分化结构的形成。我们报道,年龄较大的子宫肿瘤表达晚期胚胎发生的标志物,与畸胎瘤样的发育程序激活一致。我们还提出了远端性腺萎缩与卵母细胞肥大耦合的证据。这项研究表明,Williams Blagosklonny模型可以为秀丽隐杆线虫衰老的这一组成部分提供机制解释。它还表明,畸胎瘤和某些形式的衰老病理之间的病因相似,因为两者都是由准程序引起的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A parthenogenetic quasi-program causes teratoma-like tumors during aging in wild-type <i>C. elegans</i>.

A parthenogenetic quasi-program causes teratoma-like tumors during aging in wild-type <i>C. elegans</i>.

A parthenogenetic quasi-program causes teratoma-like tumors during aging in wild-type <i>C. elegans</i>.

A parthenogenetic quasi-program causes teratoma-like tumors during aging in wild-type C. elegans.

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.

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来源期刊
NPJ Aging and Mechanisms of Disease
NPJ Aging and Mechanisms of Disease Medicine-Geriatrics and Gerontology
自引率
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0
审稿时长
8 weeks
期刊介绍: npj Aging and Mechanisms of Disease is an online open access journal that provides a forum for the world’s most important research in the fields of aging and aging-related disease. The journal publishes papers from all relevant disciplines, encouraging those that shed light on the mechanisms behind aging and the associated diseases. The journal’s scope includes, but is not restricted to, the following areas (not listed in order of preference): • cellular and molecular mechanisms of aging and aging-related diseases • interventions to affect the process of aging and longevity • homeostatic regulation and aging • age-associated complications • translational research into prevention and treatment of aging-related diseases • mechanistic bases for epidemiological aspects of aging-related disease.
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