Researchers at Johns Hopkins have found that
epigenetic marks on DNA — chemical marks other
than the DNA sequence — do indeed change over a
person's lifetime, and that the degree of change is
similar among family members.
Reporting in the June 25 issue of the Journal of
the American Medical Association, the team
suggests that overall genome health is heritable and that
epigenetic changes occurring over one's
lifetime may explain why disease susceptibility increases
"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," said Andrew P.
Feinberg, 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,
Feinberg says, a person's epigenetic marks would change
over time. So his team embarked on an
international collaboration to see if that was true. The
researchers 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," said Vilmundur
Gudnason, professor of cardiovascular genetics at the
University of Iceland and 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
"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," said M.
Daniele Fallin, an associate professor of
epidemiology at the 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
Similar to the Icelandic population, the Utah family
members also showed varied methylation
changes over time. But the researchers 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,"
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 Dore Eccles Foundation, Fulbright Foundation
and Icelandic Student Innovation Fund.
In addition to Fallin and Feinberg, Johns Hopkins
authors on the paper are Hans Bjornsson,
Martin Sigurdsson, Rafael Irizarry, Hengmi Cui, Wenqiang Yu
and Michael Rongione.