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Thursday, July 31, 2008

Is There a Laziness Gene?

By DEIRDRE VAN DYK
A pair of couch potatoes watch TV
A pair of couch potatoes watch TV.

Have you ever wondered why you can't get off the couch and exercise — despite paying for an expensive gym membership, despite your New Year's resolutions, even despite the doctor's scolding at your last checkup? Turns out that your inertia may be coded right into your genes.

Based on some intriguing preliminary studies in animals, J. Timothy Lightfoot, a kinesiologist, and his team at the University of North Carolina, Charlotte, suggest that genetics may indeed predispose some of us to sloth. Using mice specially bred and selected according to their activity levels, Lightfoot identified 20 different genomic locations that work in tandem to influence their activity levels — specifically, how far the animals will run. Lightfoot's team is the first to identify these genetic areas and the first to figure out that they function in concert. The researchers say the areas they found on the mouse genome may have analogs in humans, and the UNC team is now gearing up to conduct a similar study in men and women. "We have put forward a fairly complete genomic map of the areas that are associated with regulation of physical activity," says Lightfoot, whose study is published in the current issue of the Journal of Heredity.

Lightfoot, who originally wanted to coach college basketball and is himself an avid athlete, began studying activity levels as a way to try to figure out why, given all we know about the overwhelming health benefits of physical activity, so many people still choose not to exercise. A lecture at Johns Hopkins University about genetics and lung disease served as Lightfoot's eureka moment, and he became interested in studying genes as our prime mover. For the new study, Lightfoot and his team bred two strains of mice — active and inactive. Researchers then crossbred two generations of the active and inactive mice, ending up with a study group of 310 genetically mixed offspring. At about 9 weeks old, each mouse was housed in an individual cage and given an exercise wheel. Researchers measured how far, how long and how fast the animals ran every day for three weeks, at the end of which the mice were genotyped.

Exercise-prone mice put in a good 5 to 8 miles per day (the equivalent of an average man running 40 to 50 miles a day) vs. 0.3 miles per day for inactive mice. While the exercise wheels of the activity-prone mice would turn all night, some of the sedentary mice devised ingenious ways to avoid activity. One stuffed wood shavings around the wheel and turned it into a bed; one used it as an, ahem, toilet; and one climbed on top of her wheel only to get a better look at the overhead sensors tracking her movements.

Although the animals' activity levels could not be entirely attributed to genes, researchers calculated that heredity accounted for about 50% of the differences in activity. They also found that activity-promoting genes were dominant traits in 75% of the exercise-loving mice. (Researchers don't know yet how often the activity-inclined genotype would naturally occur; Lightfoot says he found a fairly continuous range of activity levels, from extremely active to very low-active, in about 30 mice strains he tested.) "When we used to talk about activity, it was whether or not people decided to be active," says Lightfoot. "Now it's clear that there's an inherent drive as to whether one is active or not active."

Exactly how that drive plays out in the body is still a mystery. There are two theories, Lightfoot says: Genes may affect either the way muscles work — perhaps causing them to use energy more efficiently and preventing fatigue — or some higher-order biochemical circuit in the brain, such as levels of the neurotransmitters dopamine or serotonin. Researchers have examined the muscle tissue of the mice in the study, however, and early data, which has not yet been published, suggests that there's no difference in their function. So the researchers' best guess is that the drive to exercise is at least partly influenced by brain chemicals — a reasonable hypothesis, given that dopamine or serotonin plays a significant role in several human drives and behaviors, including hunger, addiction, mood and movement disorders like Parkinson's disease.

Chemistry is not destiny, of course. Lightfoot hopes to use his research to help determine which patients may need a bigger boost to get moving — he thinks that perhaps close supervision by trainers or rewards for exercising will encourage genetic lazybones to get to the gym. And maybe one day, he speculates, there might even be a drug to compensate for what your genes won't give you. A drug that makes you want to exercise? Now that's a pill worth swallowing.

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