01-03-2013, 06:27 AM
(This post was last modified: 01-03-2013, 02:09 PM by Administrator.)
BubR1 Protein:
Incredible 10-year journey, which had started by the discovery of laboratory raised mouse that get old fast, led scientists to trace the protein that potentially protects animals from cancer and other effects of aging. Although there are still many uncertainties related to that protein called BubR1, there are evidences that the so called protective chromosomes can improve health.
Aneuploidy Causes Cancer?
Jan van Deursen, a biologist from Mayo Clinic in Rochester (Minnesota), who conducts research on tumors, and his colleagues were originally interested in studying the common features of different tumors that are called aneuploidy tumors. Aneuploid cells have an excess or deficiency of chromosomes. Most tumor cells fall under this category, but it remains unclear whether aneuploidy causes cancer indeed.
The Experiment
Van Deursen, along with former student Darren Baker, using genetic modification of mice decreased the production of BubR1 protein that helps cells with chromosome separation after division. After reduction of BubR1 chromosomes can not be properly separated into identical daughter cells, which is why some of the new stations do not have the correct number of chromosomes. Van Deursen, Baker and colleagues have questioned whether tumors will develop in these mice.
To the great surprise, instead of mice full of tumor cells, they have got animals in which the aging process was significantly accelerated. "These mice are obviously strongly different from normal mice," said Baker, who is currently engaged in the biology of aging at the Mayo Clinic. Last year, they found that these mice may help you live longer and healthier by removing old cells, and those cells whose genetic markers indicate aging.
BubR1 gene mutations are extremely rare in humans. This syndrome is characterized by a wide range of aneuploidy, premature aging and increased risk of breast cancer. It seems that the low amount of BubR1 protein is very harmful.
On the other hand, excessive amount of the same protein has a positive effect on health. In the study published in the journal Nature Cell Biology biologists argue that mice, in which the level of BubR1 is highly increased using genetic engineering, are less prone to the development of tumor cells. For example, when normal mice were exhibited to a chemical that causes tumors in the lung and skin, all of them got a cancer. However, only 33% of mice in which extremely high levels of BubR1 are found, developed a cancer under the same conditions. They have found that in these mice the fatal forms of cancer occurred about two years later than normal, and only 15% of the genetically modified mice had died of cancer, compared with 40% of normal.
Mice Run Like Olympians
At the same time, the animals with markedly increased levels of BubR1 lived on average 15% longer than the control group, and they looked like real Olympians on a treadmill, running approximately twice as much as normal mice (200 meters compared to 100 meters). Baker, Van Deursen and colleagues therefore hypothesized that BubR1 does not affect the prolongation of life only by reducing the risk of cancer, and that this hypothesis needs to be checked.
It is of great importance to know why the disorganization of chromosomes can accelerate aging, says Dai Wei, a cell biologist at the University Langone Medical Center in New York. Although aneuploidy seems harmful, studies does not give that kind of results of its effect on animals. "We found that a low level of aneuploidy, such as the one in Van Seurden’s healthy mice, leads to a large number of tumor cells, and not to lower," says Cristina Montagna, molecular geneticist at the Albert Einstein School of Medicine in the Bronx. She and her colleague Jan Vijg collaborate with Van Deursen in study of brain BubR1 in mice. A possible explanation of their findings is that very low as well as very high aneuploidy protect of tumors because the highly aneuploid cells are so damaged that they don’t have the ability of quick division.
Still, there is hope that Van Deursen and colleagues will find a new drug that will slow aging. "We certainly have not found adverse effects of excess amount of BubR1 protein," said Paul Hasty, who studies aging and recovery of DNA at the Center for Health Sciences at the University of Texas. He added that it is necessary to reveal the mechanisms by which BubR1 achieves the desired effect, but this could be a first step in discovering the treatments that could delay aging and possibly prevent the development of cancer.
Incredible 10-year journey, which had started by the discovery of laboratory raised mouse that get old fast, led scientists to trace the protein that potentially protects animals from cancer and other effects of aging. Although there are still many uncertainties related to that protein called BubR1, there are evidences that the so called protective chromosomes can improve health.
Aneuploidy Causes Cancer?
Jan van Deursen, a biologist from Mayo Clinic in Rochester (Minnesota), who conducts research on tumors, and his colleagues were originally interested in studying the common features of different tumors that are called aneuploidy tumors. Aneuploid cells have an excess or deficiency of chromosomes. Most tumor cells fall under this category, but it remains unclear whether aneuploidy causes cancer indeed.
The Experiment
Van Deursen, along with former student Darren Baker, using genetic modification of mice decreased the production of BubR1 protein that helps cells with chromosome separation after division. After reduction of BubR1 chromosomes can not be properly separated into identical daughter cells, which is why some of the new stations do not have the correct number of chromosomes. Van Deursen, Baker and colleagues have questioned whether tumors will develop in these mice.
To the great surprise, instead of mice full of tumor cells, they have got animals in which the aging process was significantly accelerated. "These mice are obviously strongly different from normal mice," said Baker, who is currently engaged in the biology of aging at the Mayo Clinic. Last year, they found that these mice may help you live longer and healthier by removing old cells, and those cells whose genetic markers indicate aging.
BubR1 gene mutations are extremely rare in humans. This syndrome is characterized by a wide range of aneuploidy, premature aging and increased risk of breast cancer. It seems that the low amount of BubR1 protein is very harmful.
On the other hand, excessive amount of the same protein has a positive effect on health. In the study published in the journal Nature Cell Biology biologists argue that mice, in which the level of BubR1 is highly increased using genetic engineering, are less prone to the development of tumor cells. For example, when normal mice were exhibited to a chemical that causes tumors in the lung and skin, all of them got a cancer. However, only 33% of mice in which extremely high levels of BubR1 are found, developed a cancer under the same conditions. They have found that in these mice the fatal forms of cancer occurred about two years later than normal, and only 15% of the genetically modified mice had died of cancer, compared with 40% of normal.
Mice Run Like Olympians
At the same time, the animals with markedly increased levels of BubR1 lived on average 15% longer than the control group, and they looked like real Olympians on a treadmill, running approximately twice as much as normal mice (200 meters compared to 100 meters). Baker, Van Deursen and colleagues therefore hypothesized that BubR1 does not affect the prolongation of life only by reducing the risk of cancer, and that this hypothesis needs to be checked.
It is of great importance to know why the disorganization of chromosomes can accelerate aging, says Dai Wei, a cell biologist at the University Langone Medical Center in New York. Although aneuploidy seems harmful, studies does not give that kind of results of its effect on animals. "We found that a low level of aneuploidy, such as the one in Van Seurden’s healthy mice, leads to a large number of tumor cells, and not to lower," says Cristina Montagna, molecular geneticist at the Albert Einstein School of Medicine in the Bronx. She and her colleague Jan Vijg collaborate with Van Deursen in study of brain BubR1 in mice. A possible explanation of their findings is that very low as well as very high aneuploidy protect of tumors because the highly aneuploid cells are so damaged that they don’t have the ability of quick division.
Still, there is hope that Van Deursen and colleagues will find a new drug that will slow aging. "We certainly have not found adverse effects of excess amount of BubR1 protein," said Paul Hasty, who studies aging and recovery of DNA at the Center for Health Sciences at the University of Texas. He added that it is necessary to reveal the mechanisms by which BubR1 achieves the desired effect, but this could be a first step in discovering the treatments that could delay aging and possibly prevent the development of cancer.
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