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

Wang, Hongyuan, Zhao, Yuan, Zhang, Zhizhou
Biochemical and biophysical research communications 2019 v.509 no.3 pp. 694-699
Caenorhabditis elegans, DNA replication, adulthood, atrophy, colorectal neoplasms, floxuridine, intestines, longevity, mortality, pharynx, reproduction, thymidylate synthase, uterine neoplasms
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.