Nuclear hormone receptor DHR96 mediates the resistance to xenobiotics but not the increased lifespan of insulin-mutant Drosophila

Proceedings of the National Academy of Sciences of the United States of America
Sonita AfscharLinda Partridge

Abstract

Lifespan of laboratory animals can be increased by genetic, pharmacological, and dietary interventions. Increased expression of genes involved in xenobiotic metabolism, together with resistance to xenobiotics, are frequent correlates of lifespan extension in the nematode worm Caenorhabditis elegans, the fruit fly Drosophila, and mice. The Green Theory of Aging suggests that this association is causal, with the ability of cells to rid themselves of lipophilic toxins limiting normal lifespan. To test this idea, we experimentally increased resistance of Drosophila to the xenobiotic dichlordiphenyltrichlorethan (DDT), by artificial selection or by transgenic expression of a gene encoding a cytochrome P450. Although both interventions increased DDT resistance, neither increased lifespan. Furthermore, dietary restriction increased lifespan without increasing xenobiotic resistance, confirming that the two traits can be uncoupled. Reduced activity of the insulin/Igf signaling (IIS) pathway increases resistance to xenobiotics and extends lifespan in Drosophila, and can also increase longevity in C. elegans, mice, and possibly humans. We identified a nuclear hormone receptor, DHR96, as an essential mediator of the increased xenobiotic re...Continue Reading

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Citations

Jan 16, 2018·Nuclear Receptor Research·Shari BodofskyBruce Wightman
Sep 17, 2017·Molecular Systems Biology·Luke S TainLinda Partridge
Apr 16, 2020·Aging Cell·Nathaniel S WoodlingLinda Partridge
Feb 25, 2017·Frontiers in Immunology·Harry NewmarkPeter Ghazal
Apr 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Xin YangYoujun Zhang
Nov 11, 2017·Nature Communications·M Irina StefanaAlex P Gould
Jan 2, 2021·Current Opinion in Insect Science·Xianchun LiXuewei Chen
Jan 3, 2021·Current Opinion in Insect Science·Kai LuRensen Zeng
Dec 30, 2020·Current Opinion in Insect Science·Marilou VandenholeThomas Van Leeuwen
Apr 12, 2021·Pesticide Biochemistry and Physiology·Dries AmezianGaëlle Le Goff

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