Epigenetics Finds That Our Genes Are Not the Whole Story

Researchers are looking at how chemical changes can affect our DNA—and disease risk.

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For more than 15 years now, Alzheimer's researcher David Bennett has been preserving his deceased subjects' brains, both frozen and fixed (or "pickled"), believing they would someday reveal why certain individuals hurtled down the path to dementia and others, some with a genetic predisposition toward the disease and with its characteristic plaques and tangles in their brains, showed no cognitive decline. Bennett, director of the Rush Alzheimer's Disease Center at Rush University Medical Center in Chicago, is among a growing number of researchers in the new field of epigenetics who are homing in on the place where our genes and environmental factors—from tobacco, viruses, and psychological trauma to diet, exercise, and stress—may intersect to promote or protect against disease. Through years of taking detailed histories while his subjects are alive, Bennett has helped suss out some of the life elements, from education to social isolation, that affect dementia's development. The working hypothesis, Bennett explains, is that "a lot of the plaques and tangles are probably genetically determined. And a lot of whether [they] express themselves as memory loss is determined by your experiences."

Exactly how that might happen is harder to pin down. But an emerging understanding that our genes are actually directed by some other source or code has entered the scene, and Bennett's preserved brain specimens are getting their big chance to contribute. Turns out, the DNA we are born with—the blueprint that underlies our very existence, from the color of our eyes to a predisposition for developing cancer—is not the whole story. What has begun to materialize as a potentially critical piece of the disease puzzle is that our genes seem to be instructed, in part, by a driver that can manipulate which of them are switched on and off, and when. Genome, meet your boss, the epigenome, which is what scientists are calling the chemical changes that can alter gene expression. "What happens when you age could be that genes are becoming switched on or switched off in an inappropriate fashion" to result in disease, says Peter Jones, researcher and director of the Norris Comprehensive Cancer Center at the University of Southern California. This discovery is more than an academic exercise: Though we cannot change our genes, experts say these chemical changes can be altered.

And some intriguing research in men with prostate cancer further supports the notion that altering gene expression may have real implications for health. A pilot study published in 2008 and led by Dean Ornish, president of the Preventive Medicine Research Institute and professor of clinical medicine at the University of California-San Francisco, found that men were able to alter the expression of cancer-relevant genes with intensive lifestyle changes. Prior to joining the study, the 30 subjects had independently chosen not to get conventional treatment and to instead employ "watchful waiting." Ornish found the men were able to lower their prostate-specific antigen scores and diminish the activity of their tumors by exercising 30 minutes daily, doing yoga or meditating for an hour daily, boosting their social support networks, and eating a low-fat diet based primarily on fruits, vegetables, beans, and soy protein. The 500-odd genes that were favorably affected were oncogenes that help drive prostate cancer and breast cancer as well as genes that spur oxidative stress and inflammation, which are components not only of common cancers but also of heart disease, says Ornish. "In every case where we could identify the gene change, it went in a healthy direction," he explains.

[Read about how to get the very best cancer care.]

Ornish's study didn't look at what mechanism might be actually tripping the genes' regulation switches, but there are two known chemical instruments of epigenetic action. A process called DNA methylation sets down "marks" on bits of DNA and is typically thought to squelch gene expression. Another, known as histone modification, effectively loosens pieces of the nearly 6-foot-long strand of DNA that is spooled and crammed into each cell, enabling portions of its genetic instructions to play out. Bennett's brain specimens, some 800 and counting, will be inspected for signs of these activities, and that information will be cross-referenced with the details of his subjects' lives, from the richness of social networks and frequency of mental challenges to their response to stress, to see which outside factors seem to prompt these chemical changes.