Scientists have discovered a protein that seems to protect animals from cancer and other deficiencies of old age, with no downsides. The research on protein BubR1 could offer clues on how protecting chromosomes can enhance health.
Cancer biologist Jan van Deursen at the Mayo Clinic in Rochester, Minnesota, and his colleagues published their findings in the journal Nature Cell Biology¹. The scientists were first interested by aneuploidy. Aneuploid cells have too few or too many chromosomes, and nearly all cancer cells fall into this category. It’s not clear whether cancer causes aneuploidy or whether aneuploidy causes cancer. The scientists engineered mice to produce less BubR1, a protein that helps cells segregate their chromosomes when they divide. The reduction of BubR1 caused the chromosomes not to be able to properly separate into identical daughter cells, leaving some of them with the wrong number of chromosomes.
To their surprise, the animals aged very quickly instead of developing cancers. 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.
The new study suggests that genetically engineered mice that make extra BubR1 are less prone to cancer. The scientists found that when normal mice are exposed to a chemical that causes lung and skin cancer, they got cancer. But only 33% of those overexpressing BubR1 got cancer. These animals also developed fatal cancers much later than normal mice. After 2 years, only 15% of the engineered mice had died of cancer compared to roughly 40% of the normal mice.
The animals that overexpressed BubR1 also lived 15% longer than control animals and could also run twice as far as the control animals. Researchers wonder why having out of order chromosomes might accelerate aging and some suggest that both very low and very high aneuploidy can protect from cancer, perhaps because highly aneuploid cells are so damaged they don’t have the ability to quickly divide. Although aneuploidy seems less desirable, studies in the literature haven’t been consistent about its effects on animals.
More research needs to be done, but for now there’s hope that van Deursen’s group may have identified a new drug target to slow aging, and possible prevent cancer. Currently, there have been no adverse effects identified with having BubR1 overexpressed.
- Baker, D. J., Nature Cell Biology 15, 96–102 (2013) doi:10.1038/ncb2643