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

Liam D. Cassidy, Andrew R.J. Young, Christopher N.J. Young, Elizabeth J. Soilleux, Edward Fielder, Bettina M. Weigand, Anthony Lagnado, Rebecca Brais, Nicholas T. Ktistakis, Kimberley A. Wiggins, Katerina Pyrillou, Murray C.H. Clarke, Diana Jurk, Joao F. Passos, Masashi Narita

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Article number307
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Cassidy, L. D., Young, A. R. J., Young, C. N. J., Soilleux, E. J., Fielder, E., Weigand, B. M., Lagnado, A., Brais, R., Ktistakis, N. T., Wiggins, K. A., Pyrillou, K., Clarke, M. C. H., Jurk, D., Passos, J. F., & Narita, M. (2020). Temporal inhibition of autophagy reveals segmental reversal of ageing with increased cancer risk. Nature communications, 11(1), [307]. https://doi.org/10.1038/s41467-019-14187-x