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Phys Ed Gretchen Reynolds on the science of fitness.

Anyone in a running group or gym class has likely noticed that some of the participants annoyingly become much fitter than others. But exactly why some people’s bodies respond well to working out and others do not puzzles scientists.

Studies indicate, unsurprisingly, that genetics must be involved, since a particularly high or low response to exercise tends to run in families. But less has been known about which genes might be involved, and how those genes actually increase or blunt the body’s response.

Now a new study in rats adds to a growing body of data about how and why bodies respond so differently to exercise. In the study, rats with a particular set of genes responded robustly to exercise, becoming much more fit after a few weeks of running, while rats born with other genes gained little cardiovascular benefit from the same exercise program, apparently because their heart muscles didn’t react as expected.

The results raise questions about whether people who remain stubbornly unfit, no matter how diligently they work out, might want to rethink their exercise routines.

Anyone who closely examines the results of exercise-related experiments will notice that some participants get more physical bang from exercise than others. The range of response can be startlingly broad.

In a telling study published in March, for instance, 95 older, overweight men and women began five months of endurance or weight training. By the end of that time, the volunteers were, on average, 8 percent stronger or more aerobically fit (depending on which program they had followed). But 13 percent of those in the endurance group did not gain or lose aerobic capacity, and 30 percent of those in the strength-training group were no stronger.

For the new rodent study, which was published this month in The Journal of the American College of Cardiology, scientists from the University of Michigan in Ann Arbor and the Norwegian University of Science and Technology in Trondheim created two strains of rats that would or would not respond well to working out.

To do so, they first had rats run for several weeks and noted how much distance the animals added before tiring during that time, meaning how well they were adapting to the workouts.

The males that added the most mileage were bred with the females who responded likewise, and the animals that added the fewest miles to their runs were also mated to one another.

After seven generations, the scientists had rats that should have been high or low responders to exercise.

And the first part of the new experiment proved that supposition to be true. The two types of rats were set on teensy treadmills with workouts that were identical in speed and intensity. The animals completed the same training program for two months.

By the end, the rats bred to respond well to running had increased the distance that they could run before tiring by about 40 percent.

The other rats were much more resistant to training, generally losing about 2 percent of their endurance during the training.

Next the scientists examined the animals’ hearts, since differences in cardiovascular responses to exercise could be expected to originate there. Normally, the left ventricle of the heart in animals and people becomes larger and able to contract more forcefully after a period of endurance training.

So it was among the high-responding rats. Cells from their left ventricles showed structural changes associated with growth and strength. They were developing athletes’ hearts.

Not so the other rats. Cells from their left ventricles looked like those from animals that hadn’t run. There were almost no physiological adaptations.

This cellular intractability likely explains why the animals lost fitness while training, says Ulrik Wisloff, a professor at the Norwegian University of Science and Technology who led the new study. If hearts don’t adapt to the demands of exercise, then workouts will sap bodies, not strengthen them.

But perhaps the most fascinating aspect of the new study involved the scientists’ determination of the gene activity driving these adaptations. When they carefully assessed gene expression in the animals’ heart cells, they found more than 360 genes that were operating differently in the two groups of animals. Many of these genes are known to affect cell growth.

In effect, these genes direct processes that should increase the size and strength of the heart. And they were not working as effectively in the animals bred to be resistant to exercise.

Humans have these same genes in our heart cells, Dr. Wisloff said, although it is impossible at this point to know if our genes respond in precisely the same way during exercise as the genes of the rats did, Dr. Wisloff said.

He also pointed out that the interplay of genes and exercise is extremely complex, and scientists are only in the earliest stages of understanding the effects of heredity, environment, nutrition and even psychology in affecting different people’s responses to exercise.

But the potential lesson of the new study would seem to be, he said, that we should closely monitor our body’s response to exercise. If after months of training, someone is not able to run any farther than he or she could before, maybe it is time to change the intensity or frequency of the workouts or try something else, like weight training. The genes that control the body’s responses to that activity are likely to be very different than those involved in responses to aerobic exercise, Dr. Wisloff said.