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氟尿嘧啶(FUdR)对衰老病理和秀丽隐杆线虫死亡率的年龄依赖性影响。

Age-dependent effects of floxuridine (FUdR) on senescent pathology and mortality in the nematode Caenorhabditis elegans.

机构信息

School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, China; School of Marine Science and Technology, Harbin Institute of Technology, Weihai, 264209, China; Institute of Healthy Aging, University College London, London, WC1E 6BT, UK.

Institute of Healthy Aging, University College London, London, WC1E 6BT, UK.

出版信息

Biochem Biophys Res Commun. 2019 Feb 12;509(3):694-699. doi: 10.1016/j.bbrc.2018.12.161. Epub 2019 Jan 3.

Abstract

Floxuridine (5'-fluorodeoxyuridine, FUdR) acts as an inhibitor of DNA replication by binding to thymidylate synthase and is widely used to treat colorectal cancer. FUdR is also frequently used in research on aging in C. elegans since by blocking reproduction it allows maintenance of synchronous nematode populations. Here we examine age-specific effects of exposure to 50 μM FUdR on pathology and mortality. We report that initiating exposure to FUdR at late development or early adulthood reduces lifespan but later initiation increases it. Moreover, earlier initiation leads to enhancement of senescent intestinal atrophy, but amelioration of several other senescent pathologies (pharyngeal degeneration and uterine tumors). These results provide further evidence of the complex effects of FUdR on aging in C. elegans, and therefore support the argue against its routine use in studies of nematode aging due to its possible confounding effects. However, they also illustrate how effects of FUdR on aging are interesting in their own right.

摘要

氟尿嘧啶(5'-氟脱氧尿苷,FUdR)通过与胸苷酸合成酶结合,充当 DNA 复制的抑制剂,被广泛用于治疗结直肠癌。FUdR 也常用于秀丽隐杆线虫衰老研究中,因为它可以通过阻断繁殖来维持线虫种群的同步性。在这里,我们研究了暴露于 50µM FUdR 对病理学和死亡率的特定年龄影响。我们报告称,在晚期发育或成年早期开始接触 FUdR 会缩短寿命,但晚期开始接触则会延长寿命。此外,早期接触会增强衰老导致的肠道萎缩,但会改善其他几种衰老性病变(咽退化和子宫肿瘤)。这些结果进一步证明了 FUdR 对秀丽隐杆线虫衰老的复杂影响,因此反对因可能产生混杂效应而将其常规用于线虫衰老研究。然而,它们也说明了 FUdR 对衰老的影响本身就很有趣。

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