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Authors: Wilhelm, Thomas
Title: Post-reproductive inhibition of the autophagic vesicle nucleation complex extends C. elegans lifespan through the neurons
Online publication date: 21-Dec-2017
Year of first publication: 2017
Language: english
Abstract: Autophagy 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.
DDC: 570 Biowissenschaften
570 Life sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: Externe Einrichtungen
Place: Mainz
URN: urn:nbn:de:hebis:77-diss-1000017037
Version: Original work
Publication type: Dissertation
License: In Copyright
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Extent: 154 Seiten
Appears in collections:JGU-Publikationen

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