November 27, 2014
DNA Methylation And Aging

On the backbone of the DNA double helix enzymes attach methyl groups (just 1 carbon and 3 hydrogens) as a way to regulate gene expression. Some Wake Forest researchers have taken a look at whether DNA methylation is one of the mechanisms that cause diseases associated with aging.

In a study published in the current issue of Nature Communications, the researchers found age-related differences in DNA methylation in 8 percent of the 450,000 sites tested across the genome. Most of these changes did not seem to affect which cellular genes were turned on or off. However, the Wake Forest Baptist team did find a small subset of age-linked DNA methylation changes -- 1,794 of the 450,000 sites tested -- that were associated with altered gene expression. Out of this subset, 42 sites were associated with pulse pressure, a measure of vascular health that is known to change with age. "Our work suggests that most of the age-associated changes in DNA methylation do not have an obvious effect on cellular function, in this case altering gene expression, and some of them may just amount to noise," said Yongmei Liu, M.D., Ph.D., associate professor of public health sciences at Wake Forest Baptist and corresponding author of the study.

We need super cheap DNA methylation measurement methods just like we need super cheap DNA sequencing methods. We can not figure out how the body works, how it breaks down, and how to repair it without absolutely massive amounts of data. Since patterns of DNA methylation vary by cell type the methylation patterns need to be checked in many cell types in order to discover patterns. To get full picture scientists need to periodically measure DNA methylation in many cell types in a large cohort of people.

The researchers in this study used only 1,264 people. A huge reduction in testing costs would enable a scaling up of the number of people tested by a few orders of magnitude. Then a longitudinal study to track health outcomes would enable the discovery of many relationships between methylation patterns, health, and longevity.

Even once many relationships between DNA methylation and health outcomes are discovered it will be hard to use the knowledge to formulate treatments. First, it will be hard to develop drugs that reverse a methylation pattern. Even if a drug is found that can reverse a harmful methylation it might turn out that in some cell types that methylation is needed. So selective intervention will be needed in some cases.

Even worse, some methylations that occur with age are probably protective even as they lower the ability of some tissue to function. If a cell is heavily damaged then cellular division could run the risk of producing cancer. Some age-related methylations could be done to prevent cell division in damaged cells. Reversing the methylations could increase the risk of cancer even while reversing some other disease.

We might end up needing to kill cells with certain methylation patterns in order to make room for healthier cells to take over their job.

Share |      Randall Parker, 2014 November 27 10:45 PM 


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