"We're beginning to see that epigenetics stands at the center of
modern medicine because epigenetic changes, unlike DNA sequence
which is the same in every cell, can occur as a result of dietary
and other environmental exposure," says Andrew P. Feinberg, M.D.,
M.P.H, a professor of molecular biology and genetics and director of
the Epigenetics Center at the Johns Hopkins School of Medicine. "Epigenetics
might very well play a role in diseases like diabetes, autism and
cancer."
If epigenetics does contribute to such diseases through
interaction with environment or aging, says Feinberg, a person's
epigenetic marks would change over time. So his team embarked on an
international collaboration to see if that was true. They focused on
methylation-one particular type of epigenetic mark, where chemical
methyl groups are attached to DNA.
"Inappropriate methylation levels can contribute to disease-too
much might turn necessary genes off, too little might turn genes on
at the wrong time or in the wrong cell," says Vilmundur Gudnason,
MD, PhD, professor of cardiovascular genetics at the University of
Iceland director of the Icelandic Heart Association's Heart
Preventive Clinic and Research Institute. "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."
The researchers used DNA samples collected from people involved
in the AGES Reykjavik Study (formerly the Reykjavik Heart Study).
Within the study, about 600 people provided DNA samples in 1991, and
again between 2002 and 2005. Of these, the research team measured
the total amount of DNA methylation in each of 111 samples and
compared total methylation from DNA collected in 2002 to 2005 to
that person's DNA collected in 1991.
They found that in almost one-third of individuals, methylation
changed over that 11-year span, but not all in the same direction.
Some individuals gained total methylation in their DNA, while others
lost. "What we saw was a detectable change over time, which showed
us proof of the principle that an individual's epigenetics does
change with age," says M. Daniele Fallin, Ph.D., an associate
professor of epidemiology at the Johns Hopkins Bloomberg School of
Public Health. "What we still didn't know was why or how, but we
thought 'maybe this, too, is something that's heritable' and could
explain why certain families are more susceptible to certain
diseases."
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 span from 126 individuals from two- and three-generation
families.
Similar to the Icelandic population, the Utah family members also
showed varied methylation changes over time. But they found that
family members tended to have the same kind of change-if one
individual lost methylation over time, they saw similar loss in
other family members.
"We still haven't concretely figured out what this means for
health and disease, but as an epidemiologist, I think this is very
interesting, since epigenetic changes could be an important link
between environment, aging and genetic risk for disease," Fallin
says.
The research was funded by the National Institutes of Health,
Swedish Cancer Foundation, Icelandic Parliament, Huntsman General
Clinical Research Center, W. M. Keck Foundation, George S. and
Delores Doré Eccles Foundation, Fulbright Foundation and the
Icelandic Student Innovation Fund.
The research was reported in the June 25 issue of the Journal of
the American Medical Association. Authors on the paper are Hans
Bjornsson, Martin Sigurdsson, Rafael Irizarry, Hengmi Cui, Wenqiang
Yu, Michael Rongione, Fallin and Feinberg, all of Hopkins; Thor
Aspelund, Gudny Eiriksdottir and Vilmundur Gudnason of Hjartavernd,
Reykjavik, Iceland; Tomas Ekstrom of Karolinska Institute,
Stockholm, Sweden; Tamara Harris and Lenore Launer of the National
Institute on Aging, Bethesda, Md.; Mark Leppert of University of
Utah, Salt Lake City; and Carmen Sapienza of Temple University
Medical School, Philadelphia, Pa.