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From Weinberg's The Biology of Cancer: A cell that has been recently formed by mitosis must decide whether it will once again initiate a new round of active growth and division or retreat into non-growing state G0. This decision is strongly influenced by mitogenic growth factors in the cell's surroundings. Their absence or presence of anti-mitogenic growth factors will trigger the default decision to proceed from mitosis into the G0 quiescent state. Withdrawal from the cell cycle into G0 is often reversible (cell can re-enter into active growth and division), however some cells irreversibly leave the cell cycle (such as neurons).

Here comes my question : What determines in the cell whether the cell will go to reversible (quiescent) or irreversible (senescent) state of G0? I have found that it has something to do with the amount of RNA (low RNA content in reversible), but I do not understand why low RNA content means that the cell should proliferate again. And are there any other criteria that determine whether the cell will go to quiescent or irreversible state? (I am looking for exact molecules and mechanisms, the more into detail the better !)

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The answer is quite complicated. One of the major issues in understanding what factors drive senescence vs quiescence has been the absence of a clear, uniform molecular definition of senescence. That said, multiple tumour suppressors, including p16 (and the other genes that occupy the INK/ARF locus) , as well as TP53, can modulate the expression of senescence associated transcriptional programmes.

Additionally, epigenetic remodelling, including heterochromatinisation at E2F target genes (which are a major driver of cell cycle progression through the S phas) , is also known to be a feature of senescence.

A very good starting point to survey the literature surrounding the topic is https://www.nature.com/articles/nrc3960?message-global=remove

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