BY JIM KOZUBEKMARCH 21, 2019
"How responsive and sensitive a gene is to the machinery regulating its DNA methylation—so called “entropic sensitivity”—is critical for a cell’s function. Stem cells may be highly responsive to this machinery, and hence very “plastic,” while the loss of sensitivity to this machinery, and thus the gene’s increasing rigidity, seem to be hallmarks of aging and cancer. Adult cells such as intestinal cells, or liver cells, need to maintain their responsiveness to this machinery and maintain their epigenetic memory of which genes to turn on, a task that depends on its ability to listen and respond to machinery that maintains it. But aging cells are less responsive to machinery that regulates their methylation status, and are more rigid, often having long blocks of methylated or un-methylated genetic regions. These long stretches of the genome can have a lot of entropy, meaning they can change at any time, quite independently from the machinery that normally regulates their methylation. As a result, genes may be far less adaptive to turn on or off as needed in response to various environmental stimuli (as genes are needed to do, as immune cells spring into action, neurons rewire, or as cells repair and fix themselves) but these long stretches of the poorly regulated genes may also be more susceptible to double-strand breaks and other forms of catastrophic damage that can lead to cancer."
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