Revved-up protein fights aging

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An unlikely, decade-long journey that began with the discovery of a rapidly aging mouse has led scientists to a protein that seems to protect animals from cancer and other scourges of old age. There are still lots of mysteries about the protein, BubR1, but the work offers clues about how protecting chromosomes can enhance health.

Cancer biologist Jan van Deursen at the Mayo Clinic in Rochester, Minn., and his colleagues were initially interested in studying a common feature of cancers, called aneuploidy.

Aneuploid cells have too few or too many chromosomes. Van Deursen, with Darren Baker, then a graduate student, engineered mice to produce less BubR1. When the protein, which helps cells segregate their chromosomes when they divide, is reduced, chromosomes can't properly separate into identical daughter cells. Some are left with the wrong number of chromosomes.


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To their surprise, instead of tumor-filled mice, the researchers wound up with animals that aged very quickly. 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 in Nature Cell Biology, the biologists report that genetically engineered mice that make extra BubR1 are less prone to cancer and lived 15 percent longer than controls, on average.

A big question now is why having your chromosomes out of order might accelerate aging, says Wei Dai, a cell biologist at the New York University Langone Medical Center who's based in Tuxedo, N.Y.

There's hope that van Deursen's group may have identified a new drug target to slow aging.

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