000097453 001__ 97453
000097453 005__ 20210930085404.0
000097453 0247_ $$2doi$$a10.1371/journal.pgen.1009083
000097453 0248_ $$2sideral$$a121700
000097453 037__ $$aART-2020-121700
000097453 041__ $$aeng
000097453 100__ $$aBjedov, I.
000097453 245__ $$aFine-tuning autophagy maximises lifespan and is associated with changes in mitochondrial gene expression in Drosophila
000097453 260__ $$c2020
000097453 5060_ $$aAccess copy available to the general public$$fUnrestricted
000097453 5203_ $$aIncreased cellular degradation by autophagy is a feature of many interventions that delay ageing. We report here that increased autophagy is necessary for reduced insulin-like signalling (IIS) to extend lifespan in Drosophila and is sufficient on its own to increase lifespan. We first established that the well-characterised lifespan extension associated with deletion of the insulin receptor substrate chico was completely abrogated by downregulation of the essential autophagy gene Atg5. We next directly induced autophagy by over-expressing the major autophagy kinase Atg1 and found that a mild increase in autophagy extended lifespan. Interestingly, strong Atg1 up-regulation was detrimental to lifespan. Transcriptomic and metabolomic approaches identified specific signatures mediated by varying levels of autophagy in flies. Transcriptional upregulation of mitochondrial-related genes was the signature most specifically associated with mild Atg1 upregulation and extended lifespan, whereas short-lived flies, possessing strong Atg1 overexpression, showed reduced mitochondrial metabolism and up-regulated immune system pathways. Increased proteasomal activity and reduced triacylglycerol levels were features shared by both moderate and high Atg1 overexpression conditions. These contrasting effects of autophagy on ageing and differential metabolic profiles highlight the importance of fine-tuning autophagy levels to achieve optimal healthspan and disease prevention.
000097453 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000097453 590__ $$a5.917$$b2020
000097453 591__ $$aGENETICS & HEREDITY$$b27 / 175 = 0.154$$c2020$$dQ1$$eT1
000097453 592__ $$a3.587$$b2020
000097453 593__ $$aCancer Research$$c2020$$dQ1
000097453 593__ $$aEcology, Evolution, Behavior and Systematics$$c2020$$dQ1
000097453 593__ $$aMolecular Biology$$c2020$$dQ1
000097453 593__ $$aGenetics (clinical)$$c2020$$dQ1
000097453 593__ $$aGenetics$$c2020$$dQ1
000097453 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000097453 700__ $$aCochemé, H.M.
000097453 700__ $$aFoley, A.
000097453 700__ $$aWieser, D.
000097453 700__ $$aWoodling, N.S.
000097453 700__ $$aCastillo-Quan, J.I.
000097453 700__ $$aNorvaisas, P.
000097453 700__ $$aLujan, C.
000097453 700__ $$aRegan, J.
000097453 700__ $$0(orcid)0000-0002-7243-1737$$aToivonen, J.M.$$uUniversidad de Zaragoza
000097453 700__ $$aMurphy, M.P.
000097453 700__ $$aThornton, J.
000097453 700__ $$aKinghorn, K.J.
000097453 700__ $$aNeufeld, T.P.
000097453 700__ $$aCabreiro, F.
000097453 700__ $$aPartridge, L.
000097453 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética
000097453 773__ $$g16, 11 (2020), e1009083 [34 pp]$$pPLoS Genet.$$tPLoS Genetics$$x1553-7390
000097453 8564_ $$s991195$$uhttps://zaguan.unizar.es/record/97453/files/texto_completo.pdf$$yVersión publicada
000097453 8564_ $$s531688$$uhttps://zaguan.unizar.es/record/97453/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000097453 909CO $$ooai:zaguan.unizar.es:97453$$particulos$$pdriver
000097453 951__ $$a2021-09-30-08:27:10
000097453 980__ $$aARTICLE