What the Heck is Epigenetics?

If you haven’t heard the word epigenetics” yet, get used to it. You’re going to be hearing it a lot in the coming years. Now that the human genome — meaning the full picture of what makes up our DNA — has been mapped, epigenetics is the next big thing in biological science.

Why? Because the truth is that genes are only part of our DNA. Within those elegantly curving strands there are “switches” that turn certain genes “on” or “off.” Researchers suspect that changes to these switches actually alter the genes, raising or lowering our risk for disease. Randy Jirtle, PhD, professor of epigenetics in the department of biological science at North Carolina State University, in Raleigh, and a pioneer in the field explains epigenetics this way: “The genome is like a computer and the epigenetics are like software that tell the computer when, where and how to work. And, in the same vein, disease susceptibility – just like a computer – is often not just problems with the hardware but also with the software.”

Dr. Jirtle says that researchers around the world are currently trying to figure out which genes are switched on and off during every biological process, from infancy, childhood and puberty through pregnancy, menopause and old age. Line by line, scientists want to understand how exactly our genes are influenced, starting from our earliest beginnings. “Very soon after fertilization is when we are the most susceptible to mutations that will give rise to diseases in adulthood,” explains Jirtle. “When people get older is another time that is important — the cells can go back to an embryonic state” and change as a result of environmental factors.

And “environment” means practically anything around you: toxins, nutrition, exercise, pollution, stress, trauma, overwork, substance abuse, poverty. “Epigenetics can be seen as the vehicle through which the environment interacts with an individual’s genome to determine all aspects of functionality in health and disease,” says Eric Nestler, MD, PhD, Nash Family Professor and director of the Friedman Brain Institute at Mount Sinai Medical Center, in New York City. Chemical changes in cells control the degree to which a gene is expressed, he adds.

Your Choices Influence the Next Generation, Too

What the Heck is Epigenetics?What’s more, these epigenetic changes can not only affect you, they’re thought to also influence your children. “We did a study on obesity in which [we found that] fathers who were overweight were more likely to have [babies] who were overweight,” says Jirtle. This is called “transgenerational epigenetic inheritance” and is another area wide open for epigenetic research.

In fact, a few large studies have looked at the effects of events such as famine on the health of subsequent generations. One study showed that the genes of people who were exposed prenatally to famine during the Dutch Hunger Winter of 1944 and 1945 had different gene expression six generations later than did their siblings who had not been exposed.

Probably not surprisingly, much of the focus of epigenetic research right now, though, is on finding the causes of cancer. “I would say that cancer is the number-one place where this research is being done now,” confirms Dr. Nestler. “And then rheumatological [disorders] followed by cardiovascular diseases and then brain, both neurology and psychiatry.”

The Addiction Connection

Nestler, who has published a seminal work on epigenetics and drug addiction, notes that one of the cardinal features of addiction is how persistent it is. “[In our research] we are looking at how drugs change the brain to cause lifelong abnormalities,” he explains. “It still has to be proven, but we think that taking a drug changes certain nerve cells to make a person continue to want the drug. These epigenetic changes actually ‘scar’ the cell to make it respond differently … A person’s DNA sequence provides a baseline sensitivity, and then their lifetime experience and drug exposures either cause scars or protective factors.”

Nestler and his team are looking primarily at addiction to cocaine and heroin, using mice for their studies (no human trials have been done yet). He says that there are several ways this research might be implemented down the road. “Once we find the epigenetic scars, we will be able to see who is vulnerable to addiction,” he says. “And then treatment could consist of either intervening directly at the epigenetic mechanism to undo scars, or, by looking at the scars, we will find what genes are affected and target those genes.”

Ghazaleh Sadri-Vakili, PhD, assistant professor of neurology at Harvard Medical School, is also studying epigenetics in the brain: “We are looking at Huntington’s Disease, ALS and addiction, mostly. We have animal models and cellular models, and sometimes we get human brains post-mortem,” she says. “It just the beginning of this research … We need better imaging in human brains so that we can understand the mechanisms better.”

In spite of the limitations and challenges of studying the brain, Dr. Sadri-Vakili calls herself “cautiously optimistic that we can unravel some of the important changes in the epigenome [the chemical compounds on DNA that influence how genes are expressed] and match those to changes in the brain.” That would open up a world of possibilities, she says: “Once we understand the molecular changes in brain cells we could use a therapy or a drug that will balance it out for the long-term,” thereby reducing the chances of relapse and helping people maintain recovery.

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