FIGURE 2.

Unresolved questions regarding the links between aging and cancer DNAm alterations. There are several loose ends with regards to how DNAm alterations may constitute mechanistic links between aging and cancer. The classic aging‐DNAm alterations include Polycomb‐associated hypermethylation, which also occurs in cancer, but the similarities with respect to hypomethylation are less clear as tumors display much clearer global hypomethylation, which could be related to their drastic expansion, while aging‐associated loss of DNAm is linked to different chromatin signatures. On the other hand, epigenetic clocks seem to be accelerated in cancer in spite of the increased cellular plasticity and activity of cancer cells. It remains to be explained if and how somatic stem cells display epigenetic clock aging, and how this phenomenon may influence cancer development, in particular with regards to cancer stem cells.