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Nutrient sensing, growth and senescence

Lookup NU author(s): Dr Bernadette Carroll, Professor Viktor KorolchukORCiD

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


Abstract

Cell growth is dictated by a wide range of mitogenic signals, the amplitude and relative contribution of which vary throughout development, differentiation and in a tissue-specific manner. The ability to sense and appropriately respond to changes in mitogens is fundamental to control cell growth, and reduced responsiveness of nutrient sensing pathways is widely associated with human disease and ageing. Cellular senescence is an important tumour suppressor mechanism that is characterised by an irreversible exit from the cell cycle in response to replicative exhaustion or excessive DNA damage. Despite the fact that senescent cells can no longer divide, they remain metabolically active and display a range of pro-growth phenotypes that are supported in part by the mTORC1-autophagy signalling axis. As our understanding of the basic mechanisms of controlling mTORC1-autophagy activity and cell growth continues to expand, we are able to explore how changes in nutrient sensing contribute to the acquisition and maintenance of cellular senescence. Furthermore, while the protective effect of senescence to limit cellular transformation is clear, more recently, the age-related accumulation of these pro-inflammatory senescent cells has been shown to contribute to a decline in organismal fitness. We will further discuss whether dysregulation of nutrient sensing pathways can be targeted to promote senescent cell death which would have important implications for healthy ageing.


Publication metadata

Author(s): Carroll B, Korolchuk VI

Publication type: Article

Publication status: Published

Journal: FEBS journal

Year: 2018

Volume: 285

Issue: 11

Pages: 1948-1958

Print publication date: 01/06/2018

Online publication date: 15/02/2018

Acceptance date: 30/01/2018

Date deposited: 12/03/2018

ISSN (print): 1742-464X

ISSN (electronic): 1742-4658

Publisher: Wiley-Blackwell Publishing Ltd.

URL: https://doi.org/10.1111/febs.14400

DOI: 10.1111/febs.14400


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Funding

Funder referenceFunder name
BB/M023389/1Biotechnology and Biological Sciences Research Council (BBSRC)

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