Enhancing autophagy by redox regulation extends lifespan in<i>Drosophila</i>



Lennicke, Claudia, Bjedov, Ivana, Grönke, Sebastian, Menger, Katja E, James, Andrew M, Castillo-Quan, Jorge Iván, van Leeuwen, Lucie AG, Foley, Andrea, Buricova, Marcela, Adcott, Jennifer
et al (show 8 more authors) (2019) Enhancing autophagy by redox regulation extends lifespan in<i>Drosophila</i>. bioRXiv. 790378-.

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Abstract

<jats:title>Abstract</jats:title><jats:p>Dysregulation of redox homeostasis has been implicated in the ageing process and the pathology of age-related diseases. To study redox signalling by H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub><jats:italic>in vivo</jats:italic>, we established a redox-shifted model by manipulating levels of the H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>-degrading enzyme catalase in<jats:italic>Drosophila</jats:italic>. Here we report that ubiquitous over-expression of catalase robustly extends lifespan in flies. As anticipated, these flies were strongly resistant to a range of oxidative stress challenges, but interestingly were sensitive to starvation, which could not be explained by differences in levels of energy reserves. This led us to explore the contribution of autophagy, which is an important mechanism for organismal survival in response to starvation. We show that autophagy is essential for the increased lifespan upon catalase up-regulation, as the survival benefits were completely abolished upon global autophagy knock-down. Furthermore, using a specific redox-inactive knock-in mutant, we highlight the<jats:italic>in vivo</jats:italic>role of a key regulatory cysteine residue in Atg4a, which is required for the lifespan extension in our catalase model. Altogether, these findings confirm the redox regulation of autophagy<jats:italic>in vivo</jats:italic>as an important modulator of longevity.</jats:p>

Item Type: Article
Uncontrolled Keywords: 3101 Biochemistry and Cell Biology, 31 Biological Sciences, Aging, 1.1 Normal biological development and functioning, Generic health relevance
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Tech, Infrastructure and Environmental Directorate
Depositing User: Symplectic Admin
Date Deposited: 27 Aug 2021 08:56
Last Modified: 20 Jul 2024 14:34
DOI: 10.1101/790378
Open Access URL: https://www.biorxiv.org/content/10.1101/790378v1
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3134918