4.6 Article

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

期刊

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.12.161

关键词

Caenorhabditis elegans; 5-Fluoro-2 '-deoxyuridine (FUdR); Lifespan; Intestine; Senescent pathology

资金

  1. NIH Office of Research Infrastructure Programs [P40 OD010440]
  2. NSFC [31071170]
  3. Key research and development plan of Shandong Province [2016GSF115022]
  4. Natural Science Foundation of Shandong Province [ZR2018MC002]
  5. China Scholarship Council
  6. 2018 Weihai Scientific Innovation Project

向作者/读者索取更多资源

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 mu M 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. (C) 2018 Elsevier Inc. All rights reserved.

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