DNA Methylation Found to Change over Time

From the archives of online GEN, June 25, 2005

EDITOR’S NOTE: In this GEN Online News Story from 2008, “DNA Methylation Found to Change over Time,” the following quote turned out to be important and prophetic: “We’re beginning to see that epigenetics stands at the center of modern medicine because epigenetic changes, unlike the DNA sequence, which is the same in every cell, can occur as a result of dietary and other environmental exposures.”

The accompanying article by Richard Stein, MD, PhD, points out that “studies in many model organisms underscored the intimate interconnectedness between genetic and epigenetic signaling.” Thus, ongoing and future work will need to focus on both areas as they functionally operate hand in hand.

 

Pigenetic marks on DNA change over a person’s lifetime to a degree that is similar among family members, according to an international group of researchers. The group, which included scientists from Johns Hopkins University, Hjartavernd (the Icelandic Heart Association), Karolinska Institute, the National Institute of Aging, the University of Utah, and Temple University Medical School, published its findings in the June 25, 2008, issue of the Journal of the American Medical Association.

The team suggests that while overall genome health is heritable, epigenetic changes through a person’s lifetime may explain why disease susceptibility increases with age.

“We’re beginning to see that epigenetics stands at the center of modern medicine because epigenetic patterns, unlike the DNA sequence, which is the same in every cell, can change as a result of dietary and other environmental exposures,” comments Andrew P. Feinberg, MD, one of the study’s corresponding authors and a professor of molecular biology and genetics and the director of the Epigenetics Center at the Johns Hopkins School of Medicine.

If epigenetics does contribute to diseases through interaction with environment or aging, Feinberg says, a person’s epigenetic marks would change over time. To investigate this hypothesis, his team focused on methylation.

“Methylation levels can vary subtly from one person to the next, so the best way to get a handle on significant changes is to study the same individuals over time,” points out Vilmundur Gudnason, MD, PhD, another corresponding author for the study and professor of cardiovascular genetics at the University of Iceland.

The researchers used DNA samples collected from people involved in the AGES Reykjavik Study. The research team measured the total amount of DNA methylation in each of 111 samples and compared total methylation from DNA collected from 2002 to 2005 to that person’s DNA collected in 1991.

They found that in almost one-third of individuals, methylation changed over the 11-year span but not all in the same direction. Some individuals gained total methylation in their DNA, while others lost.

The team then measured total methylation changes in a different set of DNA samples collected from Utah residents of northern and western European descent. These DNA samples were collected over a 16-year period from 126 individuals.

Similar to the Icelandic population, the Utah family members also showed varied methylation changes over time. The researchers found, though, that family members tended to have the same kind of change—if one individual lost methylation over time, the researchers saw a similar loss in other family members.