It’s possible that some of us are born not to run. According to an eye-opening new genetics study of lab rats, published in The Journal of Physiology, the motivation to exercise — or not — may be at least partly inherited.

For years, scientists have been bedeviled by the question of why so few people regularly exercise when we know that we should. There are obvious reasons, including poor health and jammed schedules. But researchers have begun to speculate that genetics might also play a role, as some recent experiments suggest. In one, published last year, sets of fraternal and identical adult twins wore activity monitors to track their movements. The results indicated that the twins were more alike in their exercise habits than a shared upbringing alone would explain. Their willingness to work out or sit all day depended to a large extent on genetics, the researchers concluded.

But which genes might be involved and how any differences in the activity of those genes might play out inside the body were mysteries. So scientists at the University of Missouri recently decided to delve into those issues by creating their own avid- or anti-exercising animals.

They accomplished this task by inter-breeding normal rats that had voluntarily run on wheels in the lab. The male rats that had run the most were bred with the female rats that also had run the most; those that had run the least were likewise mated. This scheme continued through many generations, until the scientists had two distinct groups of rats, some of which would willingly spend hours on running wheels, while the others would skitter on them only briefly, if at all.

In their first experiments with these rats, the researchers found some intriguing differences in the activity of certain genes in their brains. In normal circumstances, these genes create proteins that tell young cells to grow up and join the working world. But if the genes don’t function normally, the cells don’t receive the necessary chemical messages and remain in a prolonged, feckless cellular adolescence. Such immature cells cannot join the neural network and don’t contribute to healthy brain function.

In general, these genes worked normally in the brains of the rats bred to run. But their expression was quite different in the non-runners’ brains, particularly in a portion of the brain called the nucleus accumbens, which is involved in reward processing. In humans and many animals, the nucleus accumbens lights up when we engage in activities that we enjoy and seek out.

Presumably as a result, when the scientists closely examined the brains of the two types of rats, they found that by young adulthood the animals bred to run had more mature neurons in the nucleus accumbus than did the non-runners, even if neither group had actually done much running. In practical terms, that finding would seem to indicate that the brains of pups born to the running line are innately primed to find running rewarding; all those mature neurons in the reward center of the brain could be expected to fire robustly in response to exercise.

Conversely, the rats from the reluctant-running line, with their skimpier complement of mature neurons, would presumably have a weaker innate motivation to move.

Those results would be disheartening, except that in the final portion of the experiment the scientists had reluctant runners exercise by setting them on running wheels, while also providing some born-to-run animals with wheels. After six days, the unwilling runners had accumulated far less mileage, about 3.5 kilometers (two miles) per rat, compared to almost 34 kilometers each by the enthusiasts.

But the halfhearted runners’ brains were changing. Compared to others in their family line that had remained sedentary, they now showed more mature neurons in their nucleus accumbens. That part of their brain remained less well developed than among the naturally avid rat runners, but they were responding to exercise in ways that would seem likely to make it more rewarding.

What, if anything, these findings mean for people is “impossible to know at this point,” said Frank Booth, a professor of biomedical sciences at the University of Missouri who oversaw the study. Rat brains are not human brains, and rat motivations are at best opaque.

Even so, Dr. Booth said, his group’s data would seem to suggest “that humans may have genes for motivation to exercise and other genes for motivation to sit on the couch,” and over generations, one set of these genes could begin to predominate within a family. But predispositions are never dictatorial.

“People can decide to exercise,” whatever their inheritance, Dr. Booth said, and, as his study’s final experiment suggests, they could rewire their brains so that moving becomes a pleasure.

Source: The New York Times

April 9, 2014

By Gretchen Reynolds, photo by Getty Images