Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-4109
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dc.contributor.authorWilhelm, Thomas
dc.date.accessioned2017-12-21T10:51:11Z
dc.date.available2017-12-21T11:51:11Z
dc.date.issued2017
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/4111-
dc.description.abstractAutophagy represents an ubiquitous intracellular catabolic process that delivers cytoplasmatic components to the lysosome for degradation. This study shows that key autophagy genes are detrimental in late life and shorten lifespan. This is in stark contrast to previous reports, which linked autophagy almost exclusively to cytoprotective and longevity-promoting effects. While autophagy is still positive in young worms, negative effects were only observed with advanced age. This finding is in accordance with the antagonistic pleiotropy hypothesis of aging, which predicts that some genes mediate beneficial effects early in life when natural selection is strong, but are detrimental late in life when natural selection is weak. Specifically, post-reproductive inactivation of genes governing the early autophagic step of vesicle nucleation such as bec-1, unc-51 and epg-8 strongly extend C.elegans lifespan. In contrast, no longevity was observed upon postreproductive inactivation of autophagy flux genes past the step of vesicle nucleation. The here presented data supports an age-related impairment of autophagy, which is likely at the root of its harmful effects in late life. This study further uncovers that post-reproductive inhibition of autophagosome nucleation extends lifespan primarily through neurons. Notably, this neuronal mediated lifespan extension is accompanied by improved neuronal health, reduced sarcopenia and improved mobility. The obtained results collectively hold the potential to become paradigm defining in regards to how autophagy modulates health as well as lifespan across aging. Moreover, targeting the process of vesicle nucleation may prove to be a potential therapeutic avenue in treating humans with agerelated neurodegenerative diseases.en_GB
dc.language.isoeng
dc.rightsInCopyrightde_DE
dc.rights.urihttps://rightsstatements.org/vocab/InC/1.0/
dc.subject.ddc570 Biowissenschaftende_DE
dc.subject.ddc570 Life sciencesen_GB
dc.titlePost-reproductive inhibition of the autophagic vesicle nucleation complex extends C. elegans lifespan through the neuronsen_GB
dc.typeDissertationde_DE
dc.identifier.urnurn:nbn:de:hebis:77-diss-1000017037
dc.identifier.doihttp://doi.org/10.25358/openscience-4109-
jgu.type.dinitypedoctoralThesis
jgu.type.versionOriginal worken_GB
jgu.type.resourceText
jgu.description.extent154 Seiten
jgu.organisation.departmentExterne Einrichtungen-
jgu.organisation.year2018
jgu.organisation.number0000-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.organisation.placeMainz-
jgu.subject.ddccode570
opus.date.accessioned2017-12-21T10:51:11Z
opus.date.modified2018-08-10T09:49:31Z
opus.date.available2017-12-21T11:51:11
opus.subject.dfgcode00-000
opus.organisation.stringExterne Einrichtungen: Institut für Molekulare Biologie gGmbH (IMB)de_DE
opus.identifier.opusid100001703
opus.institute.number5050
opus.metadataonlyfalse
opus.type.contenttypeDissertationde_DE
opus.type.contenttypeDissertationen_GB
jgu.organisation.rorhttps://ror.org/023b0x485
Appears in collections:JGU-Publikationen

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