オートファジーによる抗老化作用とがんリスク修飾との複雑な関係

オートファジーによる抗老化作用とがんリスク修飾との複雑な関係

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細胞制御工学研究センター 成田匡志特任教授の共著論文

“Temporal Inhibition of Autophagy Reveals Segmental Reversal of Ageing With Increased Cancer Risk”

が、 Nature Communicationsに掲載されました。

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

詳しくはこちら 

 

<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.