Show simple item record

dc.contributor.authorBjedov, Ivana
dc.contributor.authorCochemé, Helena M.
dc.contributor.authorFoley, Andrea
dc.contributor.authorWieser, Daniela
dc.contributor.authorWoodling, Nathaniel S.
dc.contributor.authorCastillo-Quan, Jorge Iván
dc.contributor.authorNorvaisas, Povilas
dc.contributor.authorLujan, Celia
dc.contributor.authorRegan, Jennifer C.
dc.contributor.authorToivonen, Janne M.
dc.contributor.authorMurphy, Michael P.
dc.contributor.authorThornton, Janet
dc.contributor.authorKinghorn, Kerri J.
dc.contributor.authorNeufeld, Thomas P.
dc.contributor.authorCabreiro, Filipe
dc.contributor.authorPartridge, Linda
dc.date.accessioned2020-12-22T18:55:19Z
dc.date.available2020-12-22T18:55:19Z
dc.date.issued2020-11-30
dc.date.submitted2019-05-18
dc.identifier.issn1553-7390
dc.identifier.otherpgenetics-d-19-00785
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/315415
dc.description.abstractIncreased 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.
dc.languageen
dc.publisherPublic Library of Science
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectResearch Article
dc.subjectBiology and life sciences
dc.subjectMedicine and health sciences
dc.titleFine-tuning autophagy maximises lifespan and is associated with changes in mitochondrial gene expression in Drosophila
dc.typeArticle
dc.date.updated2020-12-22T18:55:17Z
prism.issueIdentifier11
prism.publicationNamePLOS Genetics
prism.volume16
dc.identifier.doi10.17863/CAM.62522
dcterms.dateAccepted2020-08-26
rioxxterms.versionofrecord10.1371/journal.pgen.1009083
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Larsson, Nils-Göran
dc.contributor.orcidBjedov, Ivana [0000-0001-5894-6016]
dc.contributor.orcidCochemé, Helena M. [0000-0001-8637-0042]
dc.contributor.orcidFoley, Andrea [0000-0003-0596-5533]
dc.contributor.orcidWoodling, Nathaniel S. [0000-0002-0298-3800]
dc.contributor.orcidCastillo-Quan, Jorge Iván [0000-0002-6324-2854]
dc.contributor.orcidNorvaisas, Povilas [0000-0003-4790-9820]
dc.contributor.orcidRegan, Jennifer C. [0000-0003-2164-9151]
dc.contributor.orcidToivonen, Janne M. [0000-0002-7243-1737]
dc.contributor.orcidThornton, Janet [0000-0003-0824-4096]
dc.contributor.orcidNeufeld, Thomas P. [0000-0001-5659-4811]
dc.contributor.orcidPartridge, Linda [0000-0001-9615-0094]
dc.identifier.eissn1553-7404


Files in this item

Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)