Eating a calorie-restricted diet and being female are the best bets for living longer, at least for animals. Now scientists have discovered that some links may exist between the two.
Women live about five years longer on average than men, and a similar longevity advantage exists for other mammal species, including rats. Numerous experiments have also shown that eating a nutritionally complete diet relatively low in calories can also extend lifespan: A daily calorie decrease of 30 percent correlates to living 30 to 50 percent longer than normal for all animal species tested thus far, including mice and dogs.
To find out whether these two scenarios for longer life share common molecular mechanisms, Adamo Valle of University of the Balearic Islands in Spain and his colleagues compared male and female rats. Each gender group was separated into two groups, one fed a normal diet and the other fed a calorie-restricted diet. Valle’s team then compared the activity levels of hundreds of proteins in the animals’ livers, which help to regulate energy metabolism.
Among these proteins, 11 had different activity levels in both cases — when comparing females with males and when comparing the groups on normal or calorie-restricted diets, the team reports online and in an upcoming Journal of Proteome Research. Valle and his colleagues say it makes sense that these 11 proteins might affect longevity since they play roles in energy metabolism, antioxidant mechanisms, stress response and cardiovascular protection. Most of these proteins had not been identified in previous studies of calorie restriction and longevity.
The differences in the calorie-restricted males mimicked the pattern seen in females on a normal diet, the scientists report.
It’s the first time that scientists have found similarities between the longevity effects of gender and calorie restriction, but some scientists say that common ground is understandable.
“It doesn’t surprise me at all,” comments Peter DiStefano, chief scientific officer for Elixir Pharmaceuticals, a biotech company in Cambridge, Mass., developing diabetes drugs based on calorie-restriction research. DiStefano speculates that estrogen might cause some of these effects through the hormone’s action on the hypothalamus, a region of the brain that controls many aspects of feeding behavior and energy metabolism.Louis J. Sheehan, Esquire
Wednesday, May 20, 2009
Tuesday, May 5, 2009
a-beta 9.yt.0 Louis J. Sheehan, Esquire
Amyloid-beta is a thinking brain’s protein. A new study involving people with severe brain injuries shows that as neuronal activity increases, levels of amyloid-beta in the brain also go up.
Louis J. Sheehan, Esquire A-beta, as the protein is sometimes called, is best known for causing plaques in the brains of people with Alzheimer’s disease. It is a normal component of the brain, but scientists don’t know what it does.
Traumatic brain injuries increase the risk for Alzheimer’s disease. So to find out if brain injuries cause a spike in amyloid-beta levels that could lead to plaque formation, a team of researchers from Milan, Italy, and Washington University in St. Louis sampled fluid from the brains of 18 comatose patients. http://LOUIS-J-SHEEHAN.US
The researchers inserted devices in the patients’ brains to monitor pressure. A small catheter sipped up fluid that gathers between brain cells, and then the researchers tested the fluid for A-beta.
What the researchers found was exactly the opposite of what they expected, says David L. Brody, a neurologist at Washington University who led the study with Sandra Magnoni of the Ospedale Maggiore in Milan. Instead of seeing a spike of A-beta soon after brain injury from falls, car accidents, assaults or hemorrhages, levels of the protein started low and rose as the patients improved, the team reports in the Aug. 29 Science.
“This is a fantastic study using an extraordinarily powerful technique to study human physiology and pathophysiology,” says Bradley Hyman, director of the Alzheimer’s Disease Research Center at Massachusetts General Hospital and Harvard Medical School in Boston. “While the implications for a ‘normal’ function of A-beta are intriguing, it is still not completely clear whether the data reflect an active role for A-beta or simply establish that it is a marker for neuronal activity. Sorting this out will be fascinating.”
The results are consistent with previous studies in mice that show that A-beta is a byproduct of brain cell activity, and with studies in people that show the areas of the brain that are most active are the most prone to developing Alzheimer’s plaques, says John Cirrito, a neuroscientist at Washington University who established the link between brain cell activity and A-beta in mice but was not involved in the new study. A-beta may become a tool for monitoring brain activity in comatose patients, Cirrito suggests.
But the findings seem to contrast with preliminary results from a similar study in Sweden. Neurologist Lars Hillered at Uppsala University Hospital sampled brain fluid from eight comatose patients and found that people with diffuse brain injuries had higher levels of amyloid-beta in their brains.
“It could be that we’re onto something similar,” Hillered says. Electrical activity in brain cells and damage to cells may both raise levels of A-beta, he says.
Fluid taken by spinal tap doesn’t show the link between A-beta levels and brain activity. That is probably because the brain fluid the researchers sampled for the study came directly from the space between brain cells, while cerebral spinal fluid contains proteins filtered from blood as well as from the brain, Brody says.
Researchers still don’t know why brain injury puts people at higher risk for Alzheimer’s disease or what the protein’s normal job is in the brain.
“This study raises more questions than it answers,” Brody says. “It’s really just the beginning.”
Louis J. Sheehan, Esquire A-beta, as the protein is sometimes called, is best known for causing plaques in the brains of people with Alzheimer’s disease. It is a normal component of the brain, but scientists don’t know what it does.
Traumatic brain injuries increase the risk for Alzheimer’s disease. So to find out if brain injuries cause a spike in amyloid-beta levels that could lead to plaque formation, a team of researchers from Milan, Italy, and Washington University in St. Louis sampled fluid from the brains of 18 comatose patients. http://LOUIS-J-SHEEHAN.US
The researchers inserted devices in the patients’ brains to monitor pressure. A small catheter sipped up fluid that gathers between brain cells, and then the researchers tested the fluid for A-beta.
What the researchers found was exactly the opposite of what they expected, says David L. Brody, a neurologist at Washington University who led the study with Sandra Magnoni of the Ospedale Maggiore in Milan. Instead of seeing a spike of A-beta soon after brain injury from falls, car accidents, assaults or hemorrhages, levels of the protein started low and rose as the patients improved, the team reports in the Aug. 29 Science.
“This is a fantastic study using an extraordinarily powerful technique to study human physiology and pathophysiology,” says Bradley Hyman, director of the Alzheimer’s Disease Research Center at Massachusetts General Hospital and Harvard Medical School in Boston. “While the implications for a ‘normal’ function of A-beta are intriguing, it is still not completely clear whether the data reflect an active role for A-beta or simply establish that it is a marker for neuronal activity. Sorting this out will be fascinating.”
The results are consistent with previous studies in mice that show that A-beta is a byproduct of brain cell activity, and with studies in people that show the areas of the brain that are most active are the most prone to developing Alzheimer’s plaques, says John Cirrito, a neuroscientist at Washington University who established the link between brain cell activity and A-beta in mice but was not involved in the new study. A-beta may become a tool for monitoring brain activity in comatose patients, Cirrito suggests.
But the findings seem to contrast with preliminary results from a similar study in Sweden. Neurologist Lars Hillered at Uppsala University Hospital sampled brain fluid from eight comatose patients and found that people with diffuse brain injuries had higher levels of amyloid-beta in their brains.
“It could be that we’re onto something similar,” Hillered says. Electrical activity in brain cells and damage to cells may both raise levels of A-beta, he says.
Fluid taken by spinal tap doesn’t show the link between A-beta levels and brain activity. That is probably because the brain fluid the researchers sampled for the study came directly from the space between brain cells, while cerebral spinal fluid contains proteins filtered from blood as well as from the brain, Brody says.
Researchers still don’t know why brain injury puts people at higher risk for Alzheimer’s disease or what the protein’s normal job is in the brain.
“This study raises more questions than it answers,” Brody says. “It’s really just the beginning.”
Friday, May 1, 2009
time 0.tim.332187 Louis J. Sheehan, Esquire
Louis J. Sheehan, Esquire For the first time, a complete cancer genome, and incidentally a complete female genome, has been decoded, scientists report online Nov. 5 in Nature. In a study made possible by faster, cheaper and more sensitive methods for sequencing DNA, the researchers pinpoint eight new genes that may cause a cell to turn cancerous.
“Since cancer is a disease of the genome, this newfound ability to determine the complete DNA sequence of a cancer cell is enormously powerful,” comments Francis Collins, a geneticist and former director of the National Human Genome Research Institute in Bethesda, Md., a group that raced to sequence the first entire human genome. http://Louis-J-Sheehan.biz
“We need to know the genetic rules of cancer,” says coauthor Timothy Ley of Washington University in St. Louis. Ley and colleagues read each of the 3 billion building blocks of DNA from tumor cells in a woman with acute myeloid leukemia, or AML, a highly malignant form of blood and bone marrow cancer. Then the team compared the long string of code with one taken from noncancerous skin cells from the same woman.
This new sequencing technology, called massively parallel sequencing, makes it possible to compare the normal DNA sequence to the cancerous DNA sequence in the same patient. That, in turn, allows researchers to find individual DNA bases — the needles in a haystack of 3 billion pieces of straw — that had mutated in the cancerous cells.
Kevin Shannon, director of the Medical Scientist Training Program at the University of California, San Francisco, studies the genes that may lead to leukemia and calls this work “a major achievement,” one that is “remarkable for its rigor and precision.”
None of the researchers knew what to expect for the number of mutated genes in the cancerous cells. “We were flying blind,” says Ley. But after rigorously pruning the data to keep only the most significant mutations, the researchers identified 10 mutations, eight of which were in genes never before implicated in AML. Of these eight new mutations, none were found to be mutated in tumors from other, smaller-scale studies, suggesting that individual AML cases are distinct.
It may be that the disease is so specific doctors will need to sequence each individual with AML to determine the best course of treatment, says coauthor Elaine Mardis, also of Washington University.
At the same time, because those earlier studies did not sequence the entire genome, and because this new study had a sample size of only one patient, it is too early to tell if AML has different kinds of mutations in different patients.
So, equally possible is that common mutations in similar groups of genes may contribute to AML. Discovery of these gene networks could allow doctors to use these common pathways of disease to treat patients similarly.
“It’s fun to speculate,” Maris says, “but we just don’t know.”
Understanding the genetic basis of cancer could lead to highly personalized treatments, says Mardis. “Right now, they’re all treated the same way they were 25 years ago,” she says of AML patients. It would be nice, Mardis says, if doctors could tell their patients, “Here’s what we know about your disease, and here are your best treatment options.”
Although scientists read every base pair in the patient’s genome, they only analyzed mutations in the DNA sequences that produce proteins, an estimated meager 1 to 2 percent of the human genome. To find mutations in other regions called intergenic DNA will require intensive statistical analyses. “We haven’t finished the job,” says Ley.
Because this study was designed to find genes that were mutated in a cancer genome, researchers omitted the DNA sequences from the sex chromosomes, the Xs and Ys, when making comparisons. Little is known about the differences between a male and a female genome.
The research team currently has funding to support more cancer genome sequences in the next few years. “What we need are thousands of genomes from each cancer,” says Ley. “We’ve already started a second patient, and are nearly finished, but our hopes are to do more.”
“Since cancer is a disease of the genome, this newfound ability to determine the complete DNA sequence of a cancer cell is enormously powerful,” comments Francis Collins, a geneticist and former director of the National Human Genome Research Institute in Bethesda, Md., a group that raced to sequence the first entire human genome. http://Louis-J-Sheehan.biz
“We need to know the genetic rules of cancer,” says coauthor Timothy Ley of Washington University in St. Louis. Ley and colleagues read each of the 3 billion building blocks of DNA from tumor cells in a woman with acute myeloid leukemia, or AML, a highly malignant form of blood and bone marrow cancer. Then the team compared the long string of code with one taken from noncancerous skin cells from the same woman.
This new sequencing technology, called massively parallel sequencing, makes it possible to compare the normal DNA sequence to the cancerous DNA sequence in the same patient. That, in turn, allows researchers to find individual DNA bases — the needles in a haystack of 3 billion pieces of straw — that had mutated in the cancerous cells.
Kevin Shannon, director of the Medical Scientist Training Program at the University of California, San Francisco, studies the genes that may lead to leukemia and calls this work “a major achievement,” one that is “remarkable for its rigor and precision.”
None of the researchers knew what to expect for the number of mutated genes in the cancerous cells. “We were flying blind,” says Ley. But after rigorously pruning the data to keep only the most significant mutations, the researchers identified 10 mutations, eight of which were in genes never before implicated in AML. Of these eight new mutations, none were found to be mutated in tumors from other, smaller-scale studies, suggesting that individual AML cases are distinct.
It may be that the disease is so specific doctors will need to sequence each individual with AML to determine the best course of treatment, says coauthor Elaine Mardis, also of Washington University.
At the same time, because those earlier studies did not sequence the entire genome, and because this new study had a sample size of only one patient, it is too early to tell if AML has different kinds of mutations in different patients.
So, equally possible is that common mutations in similar groups of genes may contribute to AML. Discovery of these gene networks could allow doctors to use these common pathways of disease to treat patients similarly.
“It’s fun to speculate,” Maris says, “but we just don’t know.”
Understanding the genetic basis of cancer could lead to highly personalized treatments, says Mardis. “Right now, they’re all treated the same way they were 25 years ago,” she says of AML patients. It would be nice, Mardis says, if doctors could tell their patients, “Here’s what we know about your disease, and here are your best treatment options.”
Although scientists read every base pair in the patient’s genome, they only analyzed mutations in the DNA sequences that produce proteins, an estimated meager 1 to 2 percent of the human genome. To find mutations in other regions called intergenic DNA will require intensive statistical analyses. “We haven’t finished the job,” says Ley.
Because this study was designed to find genes that were mutated in a cancer genome, researchers omitted the DNA sequences from the sex chromosomes, the Xs and Ys, when making comparisons. Little is known about the differences between a male and a female genome.
The research team currently has funding to support more cancer genome sequences in the next few years. “What we need are thousands of genomes from each cancer,” says Ley. “We’ve already started a second patient, and are nearly finished, but our hopes are to do more.”
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