A diverse range of conditions, from mitogenic stimuli to cytotoxic stress, can induce cell senescence. Here, I propose that simultaneous stimulation of mitogen-activated pathways and downstream inhibition of cyclin-dependent kinases leads, ultimately, to cell senescence. This model distinguishes between two types of growth arrest: first, exit to G0 phase, which is caused by the withdrawal of mitogens and can lead to apoptosis; and second, hypermitogenic arrest, which is stimulated by mitogens and can lead to senescence. The concept of hypermitogenic arrest defines cell senescence as a functionally active, stable and conditionally reversible state.
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| http://dx.doi.org/10.1038/sj.embor.embor806 | DOI Listing |
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