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Temporal inhibition of autophagy reveals segmental reversal of ageing with increased cancer risk

Lookup NU author(s): Dr Ed FielderORCiD, Melanie Weigand, Dr Diana JurkORCiD, Dr Joao Passos

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

Autophagy is an important cellular degradation pathway with a central role in metabolism as well as basic quality control, two processes inextricably linked to ageing. A decrease in autophagy is associated with increasing age, yet it is unknown if this is causal in the ageing process, and whether autophagy restoration can counteract these ageing effects. Here we demonstrate that systemic autophagy inhibition induces the premature acquisition of age-associated phenotypes and pathologies in mammals. Remarkably, autophagy restoration provides a near complete recovery of morbidity and a significant extension of lifespan; however, at the molecular level this rescue appears incomplete. Importantly autophagy-restored mice still succumb earlier due to an increase in spontaneous tumour formation. Thus, our data suggest that chronic autophagy inhibition confers an irreversible increase in cancer risk and uncovers a biphasic role of autophagy in cancer development being both tumour suppressive and oncogenic, sequentially.

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Author(s): Cassidy LD, Young ARJ, Young CNJ, Soilleux EJ, Fielder E, Weigand BM, Lagnado A, Brais R, Ktistakis NT, Wiggins KA, Pyrillou K, Clarke MCH, Jurk D, Passos JF, Narita M

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2020

Volume: 11

Issue: 1

Online publication date: 16/01/2020

Acceptance date: 19/12/2019

Date deposited: 27/01/2020

ISSN (electronic): 2041-1723

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41467-019-14187-x

DOI: 10.1038/s41467-019-14187-x

PubMed id: 31949142

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