Aerobic fitness seems to alter the interior workings of cells in ways that may substantially lower the risk of breast cancer.

A new study with female rats found that those that were the most fit were much less likely than other animals to develop cancer after exposure to a known carcinogen, even if they did not exercise.

The findings offer tantalizing new clues into the relationship between fitness, exercise and malignancies.

Most of us probably think that cardiovascular fitness, which in broad, scientific terms is the ability to get oxygen and energy to muscles, is built with diligent exercise, and that the more we work out, the fitter we become. But we would be only about half right. A large percentage of our aerobic fitness, perhaps as much as half, according to some studies, is innate. This genetically determined fitness level varies widely from family to family and person to person. Exercise can augment it, while avoiding movement and gaining weight may reduce it, but people’s baseline, genetic fitness is theirs from birth.

In recent years, scientists have become interested in how our innate fitness might affect our overall health, and also why. Many studies have established that people with high fitness are at lower risk for a wide range of diseases, including many types of cancer. But whether their disease protection results from regular exercise or from a fortunate genetic heritage — or both — has been unclear.

For the new study, which was published in July in Carcinogenesis, researchers at Colorado State University, Memorial Sloan Kettering Cancer Center in New York City and the University of Michigan opted to focus on breast cancer. Epidemiological studies have shown that being physically fit is associated with lower risk for the disease, but not why.

Because they wanted to examine the role of innate fitness in the disease, the scientists turned to a famous strain of rats bred by Lauren Koch and Steven Britton at the University of Michigan. Over multiple generations, these rats were tested on treadmills. Those that ran the farthest before tiring were subsequently mated with one another, while those that pooped out early likewise were paired up, until, ultimately, the pups displayed a large difference in inborn fitness.

The researchers used female pups born to mothers with either notably high or low aerobic capacity. These young animals did not exercise, so their fitness depended almost exclusively on genetics.

Before the pups reached puberty, they were exposed to a chemical known to be a potent breast cancer trigger. The researchers then checked them frequently for palpable tumors throughout adulthood. They also looked, after the animals’ deaths, for signs of malignancies that had been too small to feel and microscopically examined breast cells for various markers of cell health.

The differences between the animals with high and low fitness turned out to be striking. The rats with low natural fitness were about four times as likely to develop breast cancer as the rats with high fitness were, and showed more tumors once the disease began. They also tended to contract the disease earlier and continue to develop tumors later in life compared with highly fit rats.

The contrasts between the two types of rats continued deep inside their cells. The researchers found almost inverted relationships in how certain aspects of the cells worked, and in particular, in the operation of what is known as the mTOR network. Shorthand for “mammalian target of rapamycin,” the mTOR network is a group of interlinked proteins within a cell that sense how much energy is available, depending on levels of oxygen and other factors, and let the cell know if there is enough energy around for it to divide and replicate.

In the rats with high fitness in this study, the mTOR networks typically produced biochemical signals that tell cells to avoid dividing much, while in the rats with low fitness, the mTOR networks pumped out messages that would generally promote cell division. Unchecked cell division is a hallmark of cancer.

Past studies have noted that women with breast cancer often show hyperactive mTOR networks.

Of course, this study involved rats, which are not people. But the findings have potential relevance for us, says Henry J. Thompson, the director of the Cancer Prevention Lab at Colorado State University and the study’s lead author.

The study underscores “the pervasive effects” of fitness on bodily health, he says. Even without exercise, the pups born with high fitness were remarkably resistant to breast cancer in this study, he says, and showed fine-tuned cell function.

Most of us are likely to be able to raise our particular innate fitness capacity with exercise, he says.

In future studies, he and his colleagues hope to use the Michigan rats to learn more about the precise types and amounts of exercise that might best augment fitness, especially in those born with low capacity, and the subsequent effects on cell health and cancer risk.

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