An unlikely decadelong journey that began with the discovery of a rapidly aging mice has led scientists to a protein that appears to protect animals against cancer and other scourges of old age without apparent disadvantages. There are still many mysteries about the protein, called BubR1, but the work offers clues on how the protective chromosomes can improve health.
Cancer biologist Jan van Deursen at the Mayo Clinic in Rochester, Minnesota, and colleagues were initially interested in studying a common feature of cancer, called aneuploidy. aneuploid cells have too few or too many chromosomes. Almost all cancer cells fall into this category, but it is unclear whether aneuploidy actually causes cancer. van Deursen, with a student can graduate, Darren Baker, engineered mice to produce less BubR1, a protein that helps cells separate from their chromosomes when they divide. When BubR1 is reduced, the chromosomes can not properly divide into identical daughter cells, leaving some girls with the wrong number of chromosomes. van Deursen, Baker, and colleagues wanted to see if these mice would develop cancer.
To their surprise, instead of the tumor-filled mice, they rolled with animals that aged very quickly. "These mice were clearly very, very different than normal mice," says Baker, who now studies the biology of aging at the Mayo Clinic. Last year they reported that the removal of old cells which, cells with a genetic marker indicating senescence of these mice could help them stay healthy longer. Adding the plot is a rare human condition caused by mutations in the gene BubR1. patients with the disease, aneuploidy syndrome variegated mosaic, age prematurely and are at high risk of cancer. Too little BubR1 seems to be bad news.
Too, on the other hand, maybe a good thing. in a work published today in Nature Cell Biology , biologists report that genetically modified mice that additional BubR1 are less prone to cancer. for example, they found that when they exposed normal mice to a product chemical that causes lung and skin tumors, all obtained cancer. But only 33% of overexpressing BubR1 to high levels did. They also found that the animals developed fatal cancers much later the mice-normal after about two years, only 15% of the mice developed cancer had died, compared with about 40% of normal mice.
The animals that overexpressed BubR1 at high levels also lived 15% longer than controls, on average. And the mouse was truly Olympian air on a treadmill, running twice as far, 0 meters instead of 100 meters, than the control animals. All that remains Baker, van Deursen and colleagues believe that the effects of BubR1 prolong life are not due only to its ability to prevent cancer, although it is not yet certain.
The big question now is why have your chromosomes out of order could accelerate aging, said Dai Wei, a cell biologist at the New York University Langone Medical Center, who is based in Tuxedo, New York. Although aneuploidy seems less desirable, the studies are not uniform about its effects on animals. "We found that when the level of aneuploidy has become weak" -As in healthy mice- van Deursen "you had more tumorigenesis," no less, said Cristina Montagna, a molecular geneticist at Albert Einstein College of Medicine in Bronx, New York . She and her colleague January Vijg collaborate with van Deursen to study the brain of its BubR1 mouse. One possibility is that both very low and very high aneuploidy may protect against cancer, perhaps because the highly aneuploid cells are so damaged that they lack the ability to divide rapidly.
Yet there is hope that the van Deursen group may have identified a new therapeutic target to slow aging. "He [are] no negative consequences it has identified" to have more BubR1 says Paul Hasty, who studies aging and DNA repair at the University of Texas Health Science Center at San Antonio. "You need to understand exactly what BubR1 done to achieve this desired effect," he adds, but this could be the first step on a long way toward new treatments that delay the aging of cancer and perhaps avoid.
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