DNA methylation in senescence, aging and cancer

In response to genotoxic stresses, cells are programmed to trigger senescence, involving metabolic slowdown and proliferation arrest, to contain deleterious effects of the damaged genetic material [1]. Two forms of senescence processes are relevant in this context: (a) Replicative Senescence (RS) in response to telomere shortening and/or reactive oxygen species (ROS) that occur during aging; (b) Oncogene Induced Senescence (OIS) in response to oncogenic mutations, such as oncogenic RAS mutations. Failure to trigger senescence can lead to tumorigenesis. Epigenetic alterations play important roles during both senescence and tumor initiation. During senescence, epigenetic alterations play important roles in stably silencing proliferation-promoting genes [2], while in tumorigenesis the epigenetic changes function in suppressing tumor suppressor genes. Here we summarize recent advances in understanding the relation and origins of senescence and tumor epigenomes, and its implications for tumorigenesis