Genetische aanleg is te veranderen met
voeding.*
In het November nummer van het toonaangevende blad Discover wordt ingegaan over epigenetica, een wetenschap die de laatste jaren sterkt evolueert. Het wordt meer en meer duidelijk dat genetische aanleg, het DNA, niet alleen bepaalde zaken bepaalt of regelt. Het zijn de epigenomen die het DNA besturen, vergelijkbaar met de software die de computer bestuurt. Met het in kaart brengen van meer dan 25.000 genomen dacht men alles te weten over het DNA, nu blijkt dat DNA niet meer is dan een computer die zonder software niets kan. De software zijn de epigenomen, de schakelaars die het DNA kunnen aan of afzetten. Uit verschillende onderzoeken van de laatste tijd blijkt dat voeding die epigenomen kan beïnvloeden waardoor schakelaars bepaald DNA kunnen aan of afzetten. Deze beïnvloeding wordt zelfs doorgegeven aan volgende generaties. Een voorbeeld: Een speciaal soort gele muizen die genetisch vatbaar zijn voor kanker en diabetes kregen enige tijd speciale voeding rijk aan methylverbindingen. Voeding rijk aan deze verbindingen zijn o.a. vis, bietjes, broccoli, knoflook, spinazie, peulvruchten, foliumzuur en vitamine B12. Wat bleek nu dat het merendeel van de nakomelingen van deze gele muizen niet meer geel waren en ongevoelig voor kanker en diabetes en ze werden ook veel ouder. Voeding had bepaalde schakelaars uitgezet waardoor de muizen genetisch anders reageerden. Tot voor kort dacht men dat deze epigenomen alleen tijdens de zwangerschap in de foetus vastgelegd werden doch zeer recent is komen vast te staan dat die periode wel belangrijk is doch dat gedurende iemands leven epigenomen ook kunnen veranderen door bijv. milieuomstandigheden of de voeding.
DNA
Is Not Destiny
The new science of epigenetics rewrites the rules of disease, heredity, and
identity.
Back
in 2000, Randy Jirtle, a professor of radiation oncology at Duke University, and
his postdoctoral student Robert Waterland designed a groundbreaking genetic
experiment that was simplicity itself. They started with pairs of fat yellow
mice known to scientists as agouti mice, so called because they carry a
particular gene—the agouti gene—that in addition to making the rodents
ravenous and yellow renders them prone to cancer and diabetes. Jirtle and
Waterland set about to see if they could change the unfortunate genetic legacy
of these little creatures.
Typically,
when agouti mice breed, most of the offspring are identical to the parents: just
as yellow, fat as pincushions, and susceptible to life-shortening disease. The
parent mice in Jirtle and Waterland's experiment, however, produced a majority
of offspring that looked altogether different. These young mice were slender and
mousy brown. Moreover, they did not display their parents' susceptibility to
cancer and diabetes and lived to a spry old age. The effects of the agouti gene
had been virtually erased.
Remarkably,
the researchers effected this transformation without altering a single letter of
the mouse's DNA. Their approach instead was radically straightforward—they
changed the moms' diet. Starting just before conception, Jirtle and Waterland
fed a test group of mother mice a diet rich in methyl donors, small chemical
clusters that can attach to a gene and turn it off. These molecules are common
in the environment and are found in many foods, including onions, garlic, beets,
and in the food supplements often given to pregnant women. After being consumed
by the mothers, the methyl donors worked their way into the developing embryos'
chromosomes and onto the critical agouti gene. The mothers passed along the
agouti gene to their children intact, but thanks to their methyl-rich pregnancy
diet, they had added to the gene a chemical switch that dimmed the gene's
deleterious effects.
"It
was a little eerie and a little scary to see how something as subtle as a
nutritional change in the pregnant mother rat could have such a dramatic impact
on the gene expression of the baby," Jirtle says. "The results showed
how important epigenetic changes could be."
Our
DNA—specifically the 25,000 genes identified by the Human Genome Project—is
now widely regarded as the instruction book for the human body. But genes
themselves need instructions for what to do, and where and when to do it. A
human liver cell contains the same DNA as a brain cell, yet somehow it knows to
code only those proteins needed for the functioning of the liver. Those
instructions are found not in the letters of the DNA itself but on it, in an
array of chemical markers and switches, known collectively as the epigenome,
that lie along the length of the double helix. These epigenetic switches and
markers in turn help switch on or off the expression of particular genes. Think
of the epigenome as a complex software code, capable of inducing the DNA
hardware to manufacture an impressive variety of proteins, cell types, and
individuals.
In
recent years, epigenetics researchers have made great strides in understanding
the many molecular sequences and patterns that determine which genes can be
turned on and off. Their work has made it increasingly clear that for all the
popular attention devoted to genome-sequencing projects, the epigenome is just
as critical as DNA to the healthy development of organisms, humans included.
Jirtle and Waterland's experiment was a benchmark demonstration that the
epigenome is sensitive to cues from the environment. More and more, researchers
are finding that an extra bit of a vitamin, a brief exposure to a toxin, even an
added dose of mothering can tweak the epigenome—and thereby alter the software
of our genes—in ways that affect an individual's body and brain for life.
The
even greater surprise is the recent discovery that epigenetic signals from the
environment can be passed on from one generation to the next, sometimes for
several generations, without changing a single gene sequence. It's well
established, of course, that environmental effects like radiation, which alter
the genetic sequences in a sex cell's DNA, can leave a mark on subsequent
generations. Likewise, it's known that the environment in a mother's womb can
alter the development of a fetus. What's eye-opening is a growing body of
evidence suggesting that the epigenetic changes wrought by one's diet, behavior,
or surroundings can work their way into the germ line and echo far into the
future. Put simply, and as bizarre as it may sound, what you eat or smoke today
could affect the health and behavior of your great-grandchildren.
All
of these discoveries are shaking the modern biological and social certainties
about genetics and identity. We commonly accept the notion that through our DNA
we are destined to have particular body shapes, personalities, and diseases.
Some scholars even contend that the genetic code predetermines intelligence and
is the root cause of many social ills, including poverty, crime, and violence.
"Gene as fate" has become conventional wisdom. Through the study of
epigenetics, that notion at last may be proved outdated. Suddenly, for better or
worse, we appear to have a measure of control over our genetic legacy.
"Epigenetics
is proving we have some responsibility for the integrity of our genome,"
Jirtle says. "Before, genes predetermined outcomes. Now everything we do—everything
we eat or smoke—can affect our gene expression and that of future generations.
Epigenetics introduces the concept of free will into our idea of genetics."
Scientists
are still coming to understand the many ways that epigenetic changes unfold at
the biochemical level. One form of epigenetic change physically blocks access to
the genes by altering what is called the histone code. The DNA in every cell is
tightly wound around proteins known as histones and must be unwound to be
transcribed. Alterations to this packaging cause certain genes to be more or
less available to the cell's chemical machinery and so determine whether those
genes are expressed or silenced. A second, well-understood form of epigenetic
signaling, called DNA methylation, involves the addition of a methyl group—a
carbon atom plus three hydrogen atoms—to particular bases in the DNA sequence.
This interferes with the chemical signals that would put the gene into action
and thus effectively silences the gene.
Until
recently, the pattern of an individual's epigenome was thought to be firmly
established during early fetal development. Although that is still seen as a
critical period, scientists have lately discovered that the epigenome can change
in response to the environment throughout an individual's lifetime.
(Nov. 2006)