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Increasing Interest in DNA Methylation in Aging

Epigenetic mechanisms such as DNA methylation alter the pace at which specific proteins are manufactured. Epigenetic patterns are constantly in flux in our cells, changing in response to circumstances, the most interesting of which is the accumulation of cellular and molecular damage that causes aging. Now that researchers have demonstrated that some patterns of DNA methylation change in a fairly reliable way with age, reliable enough to be used to determine age from tissue samples in fact, there is perhaps a greater interest in exploring the details:

Although every person's DNA remains the same throughout their lives, scientists know that it functions differently at different ages. As people age, drastic changes occur in their DNA methylation patterns, which are thought to act as a "second code" on top of the DNA that can lock genes in the on or off position. However, what the consequences of these changes are remains a mystery. To begin deciphering this process, [scientists] studied methylation patterns in the blood cells of 1,264 persons ages 55 to 94 who participated in the Multi-Ethnic Study of Atherosclerosis (MESA).

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 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. The methylation sites that are linked to altered gene expression are good candidates as potential drivers of the negative effects of aging, especially the small subset linked to pulse pressure. Our findings provide new insights into the aging process."

Future studies will try to test the relationship between these methylation sites and specific health outcomes. Eventually, the scientists hope to be able to target and reverse specific sites that are involved with age-related diseases.

Link: http://www.sciencedaily.com/releases/2014/11/141118110003.htm

Comments

The term "molecular changes" might be more appropriate since there may be some nonrandom, predictable progression of hyper-/hypo-methylation in different tissues. Some interesting similar references -

DNA methylation age and the epigenetic clock
http://labs.genetics.ucla.edu/horvath/dnamage/

DNA methylation age of human tissues and cell types
http://genomebiology.com/content/pdf/gb-2013-14-10-r115.pdf

Causes and Consequences of Age-Related Changes in DNA Methylation: A Role for ROS?
http://www.mdpi.com/2079-7737/3/2/403

Present and future of anti-ageing epigenetic diets
http://www.ideal-ageing.eu/uploads/publicaties/2014_bacalini_mechagdev.pdf

Posted by: Lou Pagnucco at November 19th, 2014 2:30 PM

How are the causes and effects of a given epigenetic change teased out? Do we have a good picture of which changes could be considered "damage", which are "protective" or "compensatory" responses to age-related damage, or which are benign?

Posted by: Seth at November 19th, 2014 3:06 PM

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