Mystery Ingredient in Coffee Boosts Protection Against Alzheimer's Disease, Study Finds

Mystery Ingredient in Coffee Boosts Protection Against Alzheimer's Disease, Study Finds

  9:59:00 AM    Science Lover

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A yet unidentified component of coffee interacts with the beverage's caffeine, which could be a surprising reason why daily coffee intake protects against Alzheimer's disease. A new Alzheimer's mouse study by researchers at the University of South Florida found that this interaction boosts blood levels of a critical growth factor that seems to fight off the Alzheimer's disease process.

The findings appear in the early online version of an article to be published June 28 in the Journal of Alzheimer's Disease. Using mice bred to develop symptoms mimicking Alzheimer's disease, the USF team presents the first evidence that caffeinated coffee offers protection against the memory-robbing disease that is not possible with other caffeine-containing drinks or decaffeinated coffee.

Previous observational studies in humans reported that daily coffee/caffeine intake during mid-life and in older age decreases the risk of Alzheimer's disease. The USF researchers' earlier studies in Alzheimer's mice indicated that caffeine was likely the ingredient in coffee that provides this protection because it decreases brain production of the abnormal protein beta-amyloid, which is thought to cause the disease.

The new study does not diminish the importance of caffeine to protect against Alzheimer's. Rather it shows that caffeinated coffee induces an increase in blood levels of a growth factor called GCSF (granulocyte colony stimulating factor). GCSF is a substance greatly decreased in patients with Alzheimer's disease and demonstrated to improve memory in Alzheimer's mice. A just-completed clinical trial at the USF Health Byrd Alzheimer's Institute is investigating GCSF treatment to prevent full-blown Alzheimer's in patients with mild cognitive impairment, a condition preceding the disease. The results of that trial are currently being evaluated and should be known soon.

"Caffeinated coffee provides a natural increase in blood GCSF levels," said USF neuroscientist Dr. Chuanhai Cao, lead author of the study. "The exact way that this occurs is not understood. There is a synergistic interaction between caffeine and some mystery component of coffee that provides this beneficial increase in blood GCSF levels."

The researchers would like to identify this yet unknown component so that coffee and other beverages could be enriched with it to provide long-term protection against Alzheimer's.

In their study, the researchers compared the effects of caffeinated and decaffeinated coffee to those of caffeine alone. In both Alzheimer's mice and normal mice, treatment with caffeinated coffee greatly increased blood levels of GCSF; neither caffeine alone or decaffeinated coffee provided this effect. The researchers caution that, since they used only "drip" coffee in their studies, they do not know whether "instant" caffeinated coffee would provide the same GCSF response.

The boost in GCSF levels is important, because the researchers also reported that long-term treatment with coffee (but not decaffeinated coffee) enhances memory in Alzheimer's mice. Higher blood GCSF levels due to coffee intake were associated with better memory. The researchers identified three ways that GCSF seems to improve memory performance in the Alzheimer's mice. First, GCSF recruits stem cells from bone marrow to enter the brain and remove the harmful beta-amyloid protein that initiates the disease. GCSF also creates new connections between brain cells and increases the birth of new neurons in the brain.



"All three mechanisms could complement caffeine's ability to suppress beta amyloid production in the brain" Dr. Cao said, "Together these actions appear to give coffee an amazing potential to protect against Alzheimer's -- but only if you drink moderate amounts of caffeinated coffee."

Although the present study was performed in Alzheimer's mice, the researchers indicated that they've gathered clinical evidence of caffeine/coffee's ability to protect humans against Alzheimer's and will soon publish those findings.

Coffee is safe for most Americans to consume in the moderate amounts (4 to 5 cups a day) that appear necessary to protect against Alzheimer's disease. The USF researchers previously reported this level of coffee/caffeine intake was needed to counteract the brain pathology and memory impairment in Alzheimer's mice. The average American drinks 1½ to 2 cups of coffee a day, considerably less than the amount the researchers believe protects against Alzheimer's.

"No synthetic drugs have yet been developed to treat the underlying Alzheimer's disease process" said Dr. Gary Arendash, the study's other lead author. "We see no reason why an inherently natural product such as coffee cannot be more beneficial and safer than medications, especially to protect against a disease that takes decades to become apparent after it starts in the brain."

The researchers believe that moderate daily coffee intake starting at least by middle age (30s -- 50s) is optimal for providing protection against Alzheimer's disease, although starting even in older age appears protective from their studies. "We are not saying that daily moderate coffee consumption will completely protect people from getting Alzheimer's disease," Dr. Cao said. "However, we do believe that moderate coffee consumption can appreciably reduce your risk of this dreaded disease or delay its onset."

The researchers conclude that coffee is the best source of caffeine to counteract the cognitive decline of Alzheimer's because its yet unidentified component synergizes with caffeine to increase blood GCSF levels. Other sources of caffeine, such as carbonated drinks, energy drinks, and tea, would not provide the same level of protection against Alzheimer's as coffee, they said.

Coffee also contains many ingredients other than caffeine that potentially offer cognitive benefits against Alzheimer's disease. "The average American gets most of their daily antioxidants intake through coffee," Dr. Cao said. "Coffee is high in anti-inflammatory compounds that also may provide protective benefits against Alzheimer's disease."

An increasing body of scientific literature indicates that moderate consumption of coffee decreases the risk of several diseases of aging, including Parkinson's disease, Type II diabetes and stroke. Just within the last few months, new studies have reported that drinking coffee in moderation may also significantly reduce the risk of breast and prostate cancers.

"Now is the time to aggressively pursue the protective benefits of coffee against Alzheimer's disease," Dr. Arendash said. "Hopefully, the coffee industry will soon become an active partner with Alzheimer's researchers to find the protective ingredient in coffee and concentrate it in dietary sources."

New Alzheimer's diagnostic guidelines, now encompassing the full continuum of the disease from no overt symptoms to mild impairment to clear cognitive decline, could double the number of Americans with some form of the disease to more than 10 million. With the baby-boomer generation entering older age, these numbers will climb even more unless an effective preventive measure is identified.

"Because Alzheimer's starts in the brain several decades before it is diagnosed, any protective therapy would obviously need to be taken for decades," Dr. Cao said. "We believe moderate daily consumption of caffeinated coffee is the best current option for long-term protection against Alzheimer's memory loss. Coffee is inexpensive, readily available, easily gets into the brain, appears to directly attack the disease process, and has few side-effects for most of us."

According to the researchers, no other Alzheimer's therapy being developed comes close to meeting all these criteria.

"Aside from coffee, two other lifestyle choices -- physical and cognitive activity -- appear to reduce the risk of dementia. Combining regular physical and mental exercise with moderate coffee consumption would seem to be an excellent multi-faceted approach to reducing risk or delaying Alzheimer's," Dr. Arendash said. "With pharmaceutical companies spending millions of dollars trying to develop drugs against Alzheimer's disease, there may very well be an effective preventive right under our noses every morning -- caffeinated coffee."

This USF study was funded by the NIH-designated Florida Alzheimer's Disease Research Center and the State of Florida.

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Prolonged TV Viewing Linked to Health Risks

Prolonged TV Viewing Linked to Health Risks

  11:08:00 PM    Science Lover

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Watching television is the most common daily activity apart from work and sleep in many parts of the world, but it is time for people to change their viewing habits. According to a new study from Harvard School of Public Health (HSPH) researchers, prolonged TV viewing was associated with increased risk of type 2 diabetes, cardiovascular disease, and premature death.

New research finds that prolonged TV viewing is 
associated with increased risk of type 2 diabetes, 
cardiovascular disease, and premature death. 
(Credit: © alessandrozocc / Fotolia)

The study appears in the June 15, 2011, edition of the Journal of the American Medical Association.

"The message is simple. Cutting back on TV watching can significantly reduce risk of type 2 diabetes, heart disease, and premature mortality," said senior author Frank Hu, professor of nutrition and epidemiology at HSPH. "We should not only promote increasing physical activity levels but also reduce sedentary behaviors, especially prolonged TV watching," said Hu.

Many people around the world divide their days largely between working, sleeping, and watching television, according to the researchers. Europeans spend an average of 40 percent of their daily free time in front of the television set; Australians, 50 percent. This corresponds to three to four hours of daily viewing -- still less than a reported average of five hours in the U.S. The negative health effects of TV viewing have been documented in prior studies, including associations with reduced physical activity levels and unhealthy diets.



Hu and first author Anders Grøntved, a doctoral student and visiting researcher in the HSPH Department of Nutrition, conducted a meta-analysis, a systematic assessment of all published studies from 1970 to 2011 that linked TV viewing with increased risk of type 2 diabetes, cardiovascular disease, and premature death. Eight large prospective cohort studies from the United States, Europe, and Australia met the researchers' criteria and were included in the meta-analysis.

The results showed that more than two hours of TV viewing per day increased risk of type 2 diabetes and cardiovascular disease, and more than three hours of daily viewing increased risk of premature death. For each additional two hours of TV viewing per day, the risk of type 2 diabetes, cardiovascular disease, and premature mortality increased by 20, 15, and 13 percent respectively. Based on disease incidence in the United States, Hu and Grøntved estimated that among 100,000 individuals per year, each 2-hour increment in TV viewing per day was associated with 176 new cases of type 2 diabetes, 38 new cases of fatal cardiovascular disease, and 104 new cases of all-cause mortality.

Hu and Grøntved found that the effect of prolonged television viewing on type 2 diabetes, which usually occurs in adults, was to some extent explained by the unfavorable influence of TV viewing on obesity. Obesity is related to unhealthy eating habits and low activity levels, major risk factors for both type 2 diabetes and cardiovascular disease.

Limitations to the meta-analysis included the relatively small number of studies and that the assessment of TV viewing was self-reported by participants. In addition, the majority of the studies did not assess the role of diet and physical activity in explaining the adverse effects of TV watching on chronic disease risk.

"Sedentary lifestyle, especially prolonged TV watching, is clearly an important and modifiable risk factor for type 2 diabetes and cardiovascular disease," said Grøntved. "Future research should also look into the effects of extensive use of new media devices on energy balance and chronic disease risk."

Support for the study was provided by the Danish Heart Foundation, Sygekassernes Helsefond (the Danish Health Fund), the Oticon Foundation, the Augustinus Foundation, and the National Institutes of Health.

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'Master Switch' Gene for Obesity and Diabetes Discovered

'Master Switch' Gene for Obesity and Diabetes Discovered

  11:56:00 AM    Science Lover

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A team of researchers, led by King's College London and the University of Oxford, have found that a gene linked to type 2 diabetes and cholesterol levels is in fact a 'master regulator' gene, which controls the behaviour of other genes found within fat in the body.

Scientists have found that a gene linked to type 2
diabetes and cholesterol levels is in fact a "master
regulator" gene, which controls the behavior of
other genes found within fat in the body.
(Credit: iStockphoto)

As fat plays a key role in susceptibility to metabolic diseases such as obesity, heart disease and diabetes, this study highlights the regulatory gene as a possible target for future treatments to fight these diseases.

Published May 15 in Nature Genetics, the study was one part of a large multi-national collaboration funded by the Wellcome Trust, known as the MuTHER study. It involves researchers from King's College London, University of Oxford, The Wellcome Trust Sanger Institute, and the University of Geneva. DeCODE Genetics also contributed to the results reported in this paper.

It was already known that the KLF14 gene is linked to type 2 diabetes and cholesterol levels but, until now, how it did this and the role it played in controlling other genes located further away on the genome was unknown.

The researchers examined over 20,000 genes in subcutaneous fat biopsies from 800 UK female twin volunteers. They found an association between the KLF14 gene and the expression levels of multiple distant genes found in fat tissue, which means it acts as a master switch to control these genes. This was then confirmed in a further independent sample of 600 subcutaneous fat biopsies from Icelandic subjects.

These other genes found to be controlled by KLF14 are in fact linked to a range of metabolic traits, including body-mass index (obesity), cholesterol, insulin and glucose levels, highlighting the interconnectedness of metabolic traits.

The KLF14 gene is special in that its activity is inherited from the mother. Each person inherits a set of all genes from both parents. But in this case, the copy of KLF14 from the father is switched off, meaning that the copy from the mother is the active gene -- a process called imprinting. Moreover, the ability of KLF14 to control other genes was entirely dependent on the copy of KLF14 inherited from the mother -- the copy inherited from the father had no effect.

Professor Tim Spector from the Department of Twin Research at King's, who led the MuTHER project, said: 'This is the first major study that shows how small changes in one master regulator gene can cause a cascade of other metabolic effects in other genes. This has great therapeutic potential particularly as by studying large detailed populations such as the twins we hope to find more of these regulators.'

Professor Mark McCarthy from the University of Oxford, who co-led the study, said: 'KLF14 seems to act as a master switch controlling processes that connect changes in the behaviour of subcutaneous fat to disturbances in muscle and liver that contribute to diabetes and other conditions. We are working hard right now to understand these processes and how we can use this information to improve treatment of these conditions.'

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Could Diabetes Be in Your Bones?

Could Diabetes Be in Your Bones?

  8:54:00 PM    Science Lover

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Our bones have much greater influence on the rest of our bodies than they are often given credit for, according to two new studies in the July 23 issue of Cell, a Cell Press publication. Both studies offer new insights into the interplay between bone and blood sugar, based on signals sent via insulin and a bone-derived hormone known as osteocalcin.

Insulin signaling in bone favors whole-body glucose 
homeostasis by activating osteocalcin(1) Insulin signals 
osteoblasts, bone cells responsible for bone formation, 
which (2) tell osteoclasts, bone cells responsible for 
resorption, to destroy old bone. Next (3), the acidic 
(low pH) conditions created by the osteoclasts activates 
osteocalcin inside the bone. Finally (4), the active 
osteocalcin released from bone travels to the pancreas 
and stimulates the release of more insulin. (Credit: Image 
provided by Columbia University Medical Center)

Mice whose bones can't respond to insulin develop high blood sugar and insulin resistance, both hallmarks of diabetes. Those symptoms are tied to a drop in osteocalcin. The findings suggest that osteocalcin, or perhaps a drug that targets bone, might hold promise in fighting the global epidemic of type 2 diabetes, according to the researchers.

"Our study reveals a key molecular link between bone remodeling and metabolism," said Gerard Karsenty of Columbia University.

"Bone is an organ that has to pay attention to where calories are going," added Thomas Clemens of Johns Hopkins University School of Medicine. "It talks to muscle, fat, the pancreas. It's a player in energy metabolism."

And perhaps that makes a lot of sense, Karsenty said. The remodeling of bone relies on two cell types, bone-building osteoblasts and bone-resorbing osteoclasts, making bone the only organ with a cell type that is entirely focused on destroying host tissue. "On a daily basis, the formation of bone is expensive in terms of energy," he said.

In fact, the idea that the skeleton is much more than a reservoir for calcium and phosphate isn't entirely new, the researchers said. Earlier evidence by Karsenty's group had shown links between bone and the fat hormone leptin. (Obese adults are significantly less likely to develop osteoporosis.)

Scientists also had evidence that osteoblasts might respond to insulin in important ways. Osteoblasts bear insulin receptors and when treated with insulin show signs of collagen synthesis and take up more glucose, Clemens' team notes. People with type 1 diabetes due to a lack of insulin can also develop weakened bones.

Karsenty's team describes bone as a multitasker. It has mechanical, hematopoietic (blood-producing) and metabolic functions. It also acts as an endocrine organ through the release of osteocalcin hormone, which favors glucose metabolism when in its active form.

Still, Clemens said he was surprised by what they saw after developing a mouse lacking insulin receptors only in their osteoblasts. "The mice started to get fat," he said. They showed changes in their biochemistry that were consistent with insulin resistance. They also had low osteocalcin levels and fewer osteoblasts to produce less bone.

With age, the animals became even fatter and developed more marked high blood sugar accompanied by severe glucose intolerance and insulin resistance. Those symptoms improved with osteocalcin treatment.

Karsenty's group presents independent evidence for the important role of insulin in bone for keeping glucose in check through osteocalcin, in what he refers to as a "feed-forward loop." But his group goes a step further to suggest that bone-resorbing osteoclasts (not just osteoblasts) have a place in this too.

Karsenty explains that bone-building osteoblasts actually control bone resorption by osteoclasts, a process that takes place under very acidic conditions. Those conditions would also favor the chemical modification necessary to produce active osteocalcin, which can escape bone to act as a hormone.

That could be important to those who take osteoporosis drugs designed to block bone resorption, Karsenty suggests. "It's a red flag," he said. "Osteoporotic patients treated with [bone resorption inhibitors] may be at risk of glucose intolerance."

The researchers include Mathieu Ferron, Columbia University, New York, NY; Jianwen Wei, Columbia University, New York, NY; Tatsuya Yoshizawa, Columbia University, New York, NY; Andrea Del Fattore, University of L'Aquila, L'Aquila, Italy; Ronald A. DePinho, Harvard Medical School, Boston, MA; Anna Teti, University of L'Aquila, L'Aquila, Italy; Patricia Ducy, Columbia University, New York, NY; and Gerard Karsenty, Columbia University, New York, NY.

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Mice Can Eat 'Junk' And Not Get Fat: Researchers Find Gene That Protects High-fat-diet Mice From Obesity

Mice Can Eat 'Junk' And Not Get Fat: Researchers Find Gene That Protects High-fat-diet Mice From Obesity

  10:47:00 AM    Science Lover

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University of Michigan researchers have identified a gene that acts as a master switch to control obesity in mice. When the switch is turned off, even high-fat-diet mice remain thin.

Both mice were fed high-fat diets for several months.
Deleting the IKKE gene in the mouse on the left protected it
against the weight gain apparent in the mouse on the right.
(Credit: Photo by Scott Galvin, U-M Photo Services)

Deleting the gene, called IKKE, also appears to protect mice against conditions that, in humans, lead to Type 2 diabetes, which is associated with obesity and is on the rise among Americans, including children and adolescents.

If follow-up studies show that IKKE is tied to obesity in humans, the gene and the protein it makes will be prime targets for the development of drugs to treat obesity, diabetes and complications associated with those disorders, said Alan Saltiel, the Mary Sue Coleman Director of the U-M Life Sciences Institute.

"We've studied other genes associated with obesity – we call them 'obesogenes' – but this is the first one we've found that, when deleted, stops the animal from gaining weight," said Saltiel, senior author of a paper to be published in the Sept. 4 edition of the journal Cell.

"The fact that you can disrupt all the effects of a high-fat diet by deleting this one gene in mice is pretty interesting and surprising," he said.

Obesity is associated with a state of chronic, low-grade inflammation that leads to insulin resistance, which is usually the first step in the development of Type 2 diabetes. In the Cell paper, Saltiel and his colleagues show that deleting, or "knocking out," the IKKE gene not only protected high-fat-diet mice from obesity, it prevented chronic inflammation, a fatty liver and insulin resistance, as well.

The high-fat-diet mice were fed a lard-like substance with 45 percent of its calories from fat. Control mice were fed standard chow with 4.5 percent of its calories from fat. The dietary regimen began when the mice were 8 weeks old and continued for 14 to 16 weeks.

The gene IKKE produces a protein kinase also known as IKKE. Protein kinases are enzymes that turn other proteins on or off. The IKKE protein kinase appears to target proteins which, in turn, control genes that regulate the mouse metabolism.

When the high-fat diet is fed to a normal mouse, IKKE protein-kinase levels rise, the metabolic rate slows, and the animal gains weight. In that situation, the IKKE protein kinase acts as a brake on the metabolism.

Knockout mice placed on the high-fat diet did not gain weight, apparently because deleting the IKKE gene releases the metabolic brake, allowing it to speed up and burn more calories, instead of storing those calories as fat.

"The knockout mice are not exercising any more than the control mice used in the study. They're just burning more energy," Saltiel said. "And in the process, they're generating a little heat, as well – their body temperature actually increases a bit."

Saltiel's team is now searching for small molecules that block IKKE protein-kinase activity. IKKE inhibitors could become candidates for drug development.

"If you find an inhibitor of this protein kinase, you should be able to obtain the same effect as knocking out the gene. And that's the goal," Saltiel said. If successful candidates are identified and drug development is pursued, a new treatment for obesity and diabetes is likely a decade away, he said.

###

First author of the Cell paper is Shian-Huey Chiang of the Life Sciences Institute. Co-authors are U-M researchers Merlijn Bazuine, Carey Lumeng, Lynn Geletka, Jonathan Mowers, Nicole White, Jing-Tyan Ma, Jie Zhou, Nathan Qi, Dan Westcott and Jennifer Delproposto. Timothy Blackwell and Fiona Yull of the Vanderbilt University School of Medicine also are co-authors.

The research was funded by the National Institutes of Health and the American Diabetes Association. All animal use was conducted in compliance with the Institute of Laboratory Animal Research's Guide for the Care and Use of Laboratory Animals and was approved by the University Committee on Use and Care of Animals at the University of Michigan.

Related links:

Life Sciences Institute:

http://www.lsi.umich.edu

Saltiel Lab:

http://www.lsi.umich.edu/facultyresearch/labs/saltiel

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