A provocative new study suggests that mice raised in spacious cages with lots of toys and companions are more resistant to cancer than mice living in standard cages. The work, which finds that exercise alone doesn't explain the anticancer effect, is drawing both excitement and skepticism.
The study builds on research dating back to the 1960s, which has found that raising mice in an "enriched environment" spurs neural growth and learning. Recent research even suggests that a stimulating cage environment late in life can help restore memory in animals with neurodegenerative disease. Neuroscientists Matthew During and Lei Cao, both of Ohio State University and Cornell University, wondered whether these profound effects on the brain could influence how the body responds to cancer.
During's team studied the course of cancer in two sets of young male mice—groups of five animals housed in a standard cage (roughly the size of a bread box) with food but nothing else, and groups of 18 to 20 mice raised in a bigger cage (about the size of a portable crib) with food, toys, a maze, running wheels, and places to hide. After the mice spent 3 to 6 weeks in their cages, the researchers injected them under the skin with melanoma cancer cells and waited for tumors to develop.
The results were a surprise, During says. Mice that spent 3 weeks in the enriched cage developed tumors that were 43% smaller in volume than those raised in normal cages. The difference in tumor mass was 77% when the mice spent 6 weeks in the special cages. And unlike mice raised in standard cages, a few of those in the enriched cages developed no tumors at all. The researchers saw similar results for two types of mice prone to colon cancer.
Exercise alone didn't explain the effect. Mice raised in a typical cage connected to a running wheel developed tumors just as massive as those that did no cardio.
The anticancer effects seem related to metabolic changes, During says. Mice raised in the enriched environment had much lower blood levels of leptin, a hormone linked to obesity and cancer; they also had higher levels of corticosterone, a stress hormone. In addition, the hypothalamuses of the enhanced cage mice had higher levels of brain-derived neurotrophic factor (BDNF), a growth factor that the researchers suggest sends signals to fat cells to produce less leptin. When the team turned BDNF off or ramped it up in the brains of the mice, they saw corresponding changes in leptin levels and in tumor size, they report in tomorrow's issue of Cell.
During speculates that the mice in the enhanced cages have "some degree of anxiety" because of living in a larger space and having more fellow mice to deal with. "It's mild stress. It's challenging the system." The mild stress signals the brain to produce more BDNF and make less cancer-promoting leptin, he suggests.
During says the results suggest that a stress-free life may be less healthy than one with slight stress. "Living a couch potato existence is not the best," During says.
Some researchers are viewing the study with caution. For one, it contradicts a large body of evidence that exercise protects against cancer, says neuroscientist Henriette Van Praag of the National Institute on Aging in Bethesda, Maryland. She says one problem with the paper is that the "runner" mice in standard cages weren't given a chance to run individually; in a group, some males may hog the running wheel. "The concept is good, but I don't think they can say conclusively that exercise is not an important factor," Van Praag says.
Physiologist John Hall of the University of Mississippi Medical Center in Jackson calls the paper "an exciting new idea," but points to another reason to question whether the results will apply to people: Beta blockers, which are drugs that block BDNF, have been in widespread use for heart disease since the 1960s, yet there's "no evidence that they promote tumor growth," he says.