To their surprise, instead of tumor-filled mice, they wound up with animals that aged very quickly. "These mice were clearly very, very different than a normal mouse," says Baker, who now studies the biology of aging at the Mayo Clinic. Last year, they reported that removing old cells—that is, cells with a genetic marker indicating senescence—from these mice could help them stay healthier longer. Adding intrigue is an extremely rare human condition caused by mutations in the BubR1 gene. Patients with the disease, mosaic variegated aneuploidy syndrome, age prematurely and have an elevated risk of cancer. Too little BubR1 seems to be bad news.
Too much, on the other hand, might be a good thing. In work published today in Nature Cell Biology, the biologists report that genetically engineered mice that make extra BubR1 are less prone to cancer. For example, they found that when they exposed normal mice to a chemical that causes lung and skin tumors, all of them got cancer. But only 33% of those overexpressing BubR1 at high levels did. They also found that these animals developed fatal cancers much later than normal mice—after about 2 years, only 15% of the engineered mice had died of cancer, compared with roughly 40% of normal mice. The animals that overexpressed BubR1 at high levels also lived 15% longer than controls, on average. And the mice looked veritably Olympian on a treadmill, running about twice as far—200 meters rather than 100 meters—as control animals. All of this left Baker, van Deursen, and their colleagues thinking that BuBR1's life-extending effects aren't due to only its ability to prevent cancer, although that's not yet certain.