000056278 001__ 56278
000056278 005__ 20200221144338.0
000056278 0247_ $$2doi$$a10.1073/pnas.1515137113
000056278 0248_ $$2sideral$$a93608
000056278 037__ $$aART-2016-93608
000056278 041__ $$aeng
000056278 100__ $$aAfschar, S
000056278 245__ $$aNuclear hormone receptor DHR96 mediates the resistance to xenobiotics but not the increased lifespan of insulin-mutant Drosophila
000056278 260__ $$c2016
000056278 5060_ $$aAccess copy available to the general public$$fUnrestricted
000056278 5203_ $$aLifespan 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 resistance of IIS mutant flies. However, the IIS mutants remained long-lived in the absence of DHR96 and the xenobiotic resistance that it conferred. Thus, in Drosophila IIS mutants, increased xenobiotic resistance and enhanced longevity are not causally connected. The frequent co-occurrence of the two traits may instead have evolved because, in nature, lowered IIS can signal the presence of pathogens. It will be important to determine whether enhanced xenobiotic metabolism is also a correlated, rather than a causal, trait in long-lived mice.
000056278 536__ $$9info:eu-repo/grantAgreement/EC/FP7/ 268739/EU/Experimental Research into Ageing/ERA
000056278 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000056278 590__ $$a9.661$$b2016
000056278 591__ $$aMULTIDISCIPLINARY SCIENCES$$b4 / 63 = 0.063$$c2016$$dQ1$$eT1
000056278 592__ $$a6.575$$b2016
000056278 593__ $$aMultidisciplinary$$c2016$$dQ1
000056278 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000056278 700__ $$0(orcid)0000-0002-7243-1737$$aToivonen, JM$$uUniversidad de Zaragoza
000056278 700__ $$aHoffmann, JM
000056278 700__ $$aTain, LS
000056278 700__ $$aWieser, D
000056278 700__ $$aFinlayson, AJ
000056278 700__ $$aDriege, Y
000056278 700__ $$aAlic, N
000056278 700__ $$aEmran, S
000056278 700__ $$aStinn, J
000056278 700__ $$aFroehlich, J
000056278 700__ $$aPiper, MD
000056278 700__ $$aPartridge, L.
000056278 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética
000056278 773__ $$g113, 5 (2016), 1321–1326$$pProc. Natl. Acad. Sci.$$tProceedings of the National Academy of Sciences$$x0027-8424
000056278 8564_ $$s1841283$$uhttps://zaguan.unizar.es/record/56278/files/texto_completo.pdf$$yVersión publicada
000056278 8564_ $$s143753$$uhttps://zaguan.unizar.es/record/56278/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000056278 909CO $$ooai:zaguan.unizar.es:56278$$particulos$$pdriver
000056278 951__ $$a2020-02-21-13:48:22
000056278 980__ $$aARTICLE