Fig. 5

Model of reversal of senescence. Following serial passage, normal HMEC cultures eventually undergo p16-mediated cellular senescence and enter a state of deep senescence (DS). In this work, we have identified senDMP signatures and demonstrate that these are specific to the DS state and not the p16 status of the cells per se. Human senDMP signatures shows strong positive correlations with cancers from a broad range of tissues as well as ageing-associated methylomic dynamics. Senescence acts as an essential barrier to tumour progression. Overcoming this cellular programme, in combination with additional mutations, is believed to give rise to cancer. One possible interpretation of these findings is that cells which overcome senescence retain this senDMP signature as they progress towards cancer. We also describe the reversal of senescence, during which the senDMP signature essentially reverts to that seen in early proliferating (EP) cultures. This demonstrates that the senDMP signature has the potential to be dynamic