Nutrient sensing, growth and senescence.

Publisher: Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies Country of Publication: England NLM ID: 101229646 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1742-4658 (Electronic) Linking ISSN: 1742464X NLM ISO Abbreviation: FEBS J Subsets: MEDLINE

Original Publication: Oxford, UK : Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies, c2005-

Genetic Fitness*; Aging/*genetics ; Cellular Senescence/*genetics ; Mitogens/*genetics; Autophagy/genetics ; Cell Proliferation ; DNA Damage/genetics ; Humans ; Mechanistic Target of Rapamycin Complex 1/genetics ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mitogens/metabolism ; Nutrients/metabolism ; Signal Transduction

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.
(© 2018 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

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United Kingdom Biotechnology and Biological Sciences Research Council

Keywords: ageing; autophagy; growth; mTORC1; membrane potential; primary cilia; senescence

0 (Mitogens)
EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)

Date Created: 20180207 Date Completed: 20190401 Latest Revision: 20240327

20240327

PMC6001427

10.1111/febs.14400

29405586