The role of replicative senescence in cancer and human ageing: utility (or otherwise) of murine models

Cytogenetic and Genome Research
S K Smith, David Kipling

Abstract

Replicative senescence has the potential both to act as an anti-tumour mechanism, and to contribute to age-related changes in tissue function. Studies on human cells have revealed much, both about the nature of cell division counters, some of which utilize the gradual erosion of chromosomal telomeres, and the downstream signalling pathways that initiate and maintain growth arrest in senescence. A powerful test of the hypothesis that senescence is linked to either ageing or tumour prevention now requires a suitable animal model system. Here we overview the current understanding of replicative senescence in human cells, and address to what extent the senescence of murine cells in culture mirrors this phenomenon. We also discuss whether examples of telomere-independent senescence, such as those seen in mouse embryonic fibroblasts (MEFs) and several human cells types, should be viewed not as a consequence of "inadequate growth conditions", but rather as a powerful potential model system to dissect the selective pressures that occur in the early stages of tumour development, ones that we speculate lead to the observed high frequency of abrogation of p16INK4a function in human cancer.

Citations

May 28, 2011·European Journal of Cell Biology·Steffen KrausDorit K Nägler
Aug 19, 2015·Frontiers in Oncology·Abdelouahid ElkhattoutiChristian R Gomez
Nov 30, 2012·Plastic and Reconstructive Surgery·Parag ButalaStephen M Warren
Mar 20, 2015·Age·D G A Burton, R G A Faragher
Jan 13, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Evelyne PeuchantSandrine Dabernat
Jul 15, 2015·Oncotarget·Morten F GjerstorffHenrik J Ditzel

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