Cell Replication Changes the Epigenome in Ways that Connect to Cancer

Researchers here demonstrate that one can create a signature of replication-based epigenetic change in cells, and that this signature is stronger in old tissues and cancerous tissues. This leads to a view in which increased replication stress on cells in a tissue, meaning a tissue that is made up of cells that have divided more times on average, have shorter telomeres, and are closer to the Hayflick limit, creates an environment that is epigenetically predisposed towards cancer. Looking at this another way, aging is characterized by reduced stem cell function, meaning a lower pace of creation of daughter somatic cells to replace losses in a tissue. It seems inevitable that this must lead to a tissue in which the average somatic cell has replicated a greater number of times, and is thus more at risk of cancerous transformation. Mutations are not the only, or perhaps even the most important, molecular events that result from cellular proliferation. We and others have shown that DNA methylation (DNAm) is also substantially altered as a direct function of cell division. Further, the epigenome has been shown to undergo dramatic changes with aging and is implicated in establishing, driving, and maintaining many cancers. Coincidently, the DNAm changes observed in aging, cancer, and proliferation share some notable patterns. In general, they tend to be characterized by gains in methylation at promoters - especially those marked by polycomb group (PcG) factor targets ...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs