Scientists Discover Genetic Link to Longevity

A link between a certain genetic variation associated with active personality traits in humans - and longer life has been uncovered by scientists.This derivative of a dopamine-receptor gene - called the DRD4 7R allele - appears in significantly higher rates in people more than 90 years old and is linked to lifespan increases in mouse studies. 
Robert Moyzis, professor of biological chemistry at UC Irvine, and Dr. Nora Volkow, a psychiatrist who conducts research at the Brookhaven National Laboratory and also directs the National Institute on Drug Abuse, led a research effort that included data from the UC Irvine-led 90+ Study in Laguna Woods, Calif. 
The variant gene is part of the dopamine system, which facilitates the transmission of signals among neurons and plays a major role in the brain network responsible for attention and reward-driven learning. The DRD4 7R allele blunts dopamine signaling, which enhances individuals' reactivity to their environment. 
People who carry this variant gene, Moyzis said, seem to be more motivated to pursue social, intellectual and physical activities. The variant is also linked to attention-deficit/hyperactivity disorder and addictive and risky behaviors. 
"While the genetic variant may not directly influence longevity," Moyzis said, "it is associated with personality traits that have been shown to be important for living a longer, healthier life. It's been well documented that the more you're involved with social and physical activities, the more likely you'll live longer. It could be as simple as that." 
Numerous studies - including a number from the 90+ Study - have confirmed that being active is important for successful aging, and it may deter the advancement of neurodegenerative diseases, such as Alzheimer's. 
Prior molecular evolutionary research led by Moyzis and Chuansheng Chen, UC Irvine professor of psychology and social behavior, indicated that this "longevity allele" was selected for during the nomadic out-of-Africa human exodus more than 30,000 years ago. 
In the new study, the UC Irvine team analyzed genetic samples from 310 participants in the 90+ Study. This "oldest-old" population had a 66 percent increase in individuals carrying the variant relative to a control group of 2,902 people between the ages of 7 and 45. The presence of the variant also was strongly correlated with higher levels of physical activity. 
Next, Volkow, neuroscientist Panayotis Thanos and their colleagues at the Brookhaven National Laboratory found that mice without the variant had a 7 percent to 9.7 percent decrease in lifespan compared with those possessing the gene, even when raised in an enriched environment. 
While it's evident that the variant can contribute to longevity, Moyzis said further studies must take place to identify any immediate clinical benefits from the research. "However, it is clear that individuals with this gene variant are already more likely to be responding to the well-known medical adage to get more physical activity," he added. 
The study has been published online in The Journal of Neuroscience.
Source-ANI
  

 

Cholesterol medicine affects energy production in muscles

PAINFUL SIDE EFFECTS

Up to 75 per cent of patients who take statins to treat elevated cholesterol levels may suffer from muscle pain. Scientists at the Center for Healthy Aging at the University of Copenhagen have now identified a possible mechanism underlying this unfortunate side effect. The results have just been published in the well-reputed Journal of American College of Cardiology.

Statin is a class of drugs which are used to treat high levels of blood cholesterol by way of inhibiting the liver’s ability to produce cholesterol. Statins are the most potent drugs on the market for lowering low-density cholesterol (LDL). At present 600,000 Danes with elevated cholesterol levels take statins daily. 30-40 per cent of the older Danish population (ages 65+) are currently undergoing treatment.

From 30-40% of the older Danish population (ages 65+) are currently undergoing treatment with statins.

"A well-known side effect of statin therapy is muscle pain. Up to 75 per cent of the physically active patients undergoing treatment for high cholesterol experience pain. This may keep people away from either taking their medicine or from taking exercise - both of which are bad choices," says Professor Flemming Dela from theCenter for Healthy Aging at the University of Copennhagen. He continues:

"We have now shown that statin treatment affects the energy production in muscles. We are working on the assumption that this can be the direct cause of muscle weakness and pain in thepatients."

Scientists also showed that the patients examined who were being treated with statins had low levels of the key protein Q10. Q10 depletion and ensuing lower energy production in the muscles could be the biological cause of the muscle pain that is a problem for many patients. 

Side effects of statin therapy

About 40 per cent of the patients being treated with statins in Denmark are in so-called ’mono therapy’ and thus are prescribed only this one drug. Presumably these are people who ‘only’ have high cholesterol and no other risk factors that could influence heart health:

"The effect of statins is marginal for these patients – in a previous published Cochrane analysis only 0.5% reduction in all-cause mortality was detected, indicating that for every 200 patients taking statins daily for five years, one death would be prevented. This patient group is obviously interesting in light of the side effects of statin therapy," comments Professor Flemming Dela.

The media influence patients

"The new study is the basis for a large planned research project, where we will focus broadly on patients undergoing statin treatment. We will look at statin consumption from a medical point of view, and will also investigate the media’s influence on patients’ acceptance or rejection of statins as a treatment option. Many contradictory views find their way into the public forum, and it can be difficult for patients to distinguish between fact and fiction," continues Professor Flemming Dela.

Scientists will also be looking at how home-monitoring of cholesterol levels influences patients – for example, does it make patients feel more or less secure when they take responsibility for their own health in this manner? The Center for Healthy Aging is currently seeking funding for the research project.

Source: University of Copennhagen

Revolutionary techniques could help harness patients' own immune cells to fight disease

Combination of diet and exercise may be as beneficial as drugs

Obese, postmenopausal women are at greater risk for developing breast cancer and their cancers tend to be more aggressive than those in lean counterparts. A University of Colorado Cancer Center study published in the December issue of the journal Cancer Research shows how this risk might be prevented.
"By using nutrient tracers for fat and sugar, we tracked where the body stored excess calories. In lean models, excess fat and glucose were taken up by the liver, mammary and skeletal tissues. In obese models, excess fat and glucose were taken up by tumors, fueling their growth," says Erin Giles, PhD, postdoctoral researcher at the CU Cancer Center and the paper's lead author.
In short, if you are lean, excess calories go to healthy tissue. If you are obese, excess calories feed the tumor.
"This implies that the menopausal window may be an opportunity for women to control their breast cancer risk through weight management," Giles says.
In this study, Giles worked with a team of scientists including postdoctoral fellows Elizabeth Wellberg and Sonali Jindal, as well as faculty members Steve Anderson, Pepper Schedin, Ann Thor and Paul Maclean. Their study also showed that tumors from obese animals had increased levels of the progesterone receptor, and this receptor appears to give tumors a metabolic advantage for growth. To extend their findings to humans, they recruited gene analysis experts David Astling and Aik-Choon Tan who analyzed 585 human breast cancers and found that human tumors expressing the progesterone receptor had the same metabolic advantage.
"Basically, we saw an abnormal metabolic response to fat and sugar in the obese that, in many ways, mirrors the response to fat and sugar in Type II diabetes," Giles says. Noticing this similarity, the group tested the use of the common Type II diabetes drug, Metformin, in their model of postmenopausal breast cancer.
"With treatment, tumor size was dramatically decreased in the obese, and tumors showed reduced expression of the progesterone receptor," Giles says.
Using a pre-clinical model, the investigators found that weight gain during menopause is particularly bad for those who are obese when entering menopause. Together, the results of this study suggest that the combination of obesity and weight gain during menopause can impact breast cancer in two ways. First, tumors that arise in obese women appear to have a metabolic advantage, and second, the inability to store excess calories in healthy tissues may further fuel tumor growth.
"While drugs may be useful in controlling breast cancer risk in obese, postmenopausal women, our results imply that a combination of diet and exercise may be equally if not more beneficial," Giles says.
The group's ongoing studies are testing whether interventions such as diet and exercise, during the period of menopausal weight gain, can improve tumor outcomes.
Source:Cell Press 

Vitamin D can help infection-prone patients avoid respiratory tract infection

Treating infection-prone patients over a 12-month period with high doses of vitamin D reduces their risk of developing respiratory tract infection – and consequently their antibiotic requirement. This according to a new study by researchers at Karolinska Institutet and Karolinska University Hospital published in the online scientific journal BMJ Open.
"Our research can have important implications for patients with recurrent infections or a compromised immune defence, such as a lack of antibodies, and can also help to prevent the emerging resistance to antibiotics that come from overuse," says Peter Bergman, researcher at Karolinska Institutet's Department of Laboratory Medicine and doctor at Karolinska University Hospital's Immunodeficiency Unit. "On the other hand, there doesn't seem to be anything to support the idea that vitamin D would help otherwise healthy people with normal, temporary respiratory tract infections."
Vitamin D is synthesised in the skin through exposure to sunlight and obtained through certain foods. In Sweden there is a seasonal variation in vitamin D in the blood, the trough coming during the darker half of the year. Studies have shown that low levels of vitamin D can increase the risk of infection, and it has long been known that the vitamin can also activate the immune defence.
For the present study now published in BMJ Open the researchers examined whether treatment with vitamin D can prevent and relieve respiratory tract infections in particularly infection-prone patients. All the 140 participants from the Immunodeficiency Unit had symptoms of disease in their respiratory tracts for at least 42 days prior to the study. The patients were randomly divided into two groups, one of which received vitamin D in relatively high doses, the other a placebo. They were also asked to keep a diary recording their state of health every day during the year-long study period.
The results show that symptoms of respiratory tract infection declined by almost a quarter and the use of antibiotics by almost half. Vitamin D treatment was also tolerated well by all patients and gave no serious side-effects.
The effect of vitamin D on respiratory tract infection is controversial, and a major study from New Zeeland published recently in the scientific journal JAMA found that it did not reduce the incidence or severity of viral respiratory tract infections. However, the present study differs from the JAMA study in several important respects, which could explain their different results. The JAMA study examined a group of healthy people with initially normal levels of vitamin D in the blood, and used bolus dose administration (i.e. large doses on fewer occasions), which is thought to be less effective that daily doses.
"However, the most important difference is probably due to the fact that our participants had much lower initial levels of vitamin D than those in the New Zealand study," says Dr Anna-Carin Norlin, doctoral student and co-lead author of the study along with Dr Bergman. "There is evidence from previous studies that vitamin D supplements are only effective in patients who fall well below the recommended level, which also suggests that it would be wise to check the vitamin D levels of patients with recurrent infections."
source:Karolinska Institutet 

A Fork That Tries to Talk as You Eat

Japanese inventors have created a new fork, the EsTheremine, which makes bizarre sounds and even attempts to talk as you eat your food, the Daily Mail reports.Containing a micro controller, a speaker, amplifier and battery within its handle, the fork generates any one of a variety of sounds depending on the type of food being eaten. 

The video shows a woman enjoying bites of numerous types of food as the fork produces some rather odd sound effects and even speaks to her. 
The sounds are apparently generated by the resistance value of the food as it is bitten off the fork - the noise it produces as she eats a chicken nugget sounds remarkably similar to a chicken clucking. 
When the young lady in the video tucks in to a piece of tempura, the fork proclaims 'Garigori' and 'shori' while a stick of cheese produces the word 'Paku'. 
Apparently longer pieces of food will cause the fork to produce multiple sounds and words while they are eaten. 
The fork can even distinguish between different types of eating, as when the young lady licks ice-cream off it, it produces a rather high pitched and fast spoken 'pakupaku'. 
The developers are a research group from the Ochanomizu University in Tokyo whose aim was to inspire people to try different types of food and encourage a more varied diet. 
The manufactures also suggest that the fork be used as a communication tool for couples and the video shows a grinning couple as the women feeds the man a mouthful and the fork pipes up with 'Pakupaku.'

Source-ANI

 

Why good resolutions about taking up a physical activity can be hard to keep

Physical inactivity is a major public health problem that has both social and neurobiological causes. According to the results of an Ipsos survey published on Monday 31 December, the French have put “taking up a sport” at the top of their list of good resolutions for 2013. However, Francis Chaouloff, research director at Inserm’s NeuroCentre Magendie (Inserm Joint Research Unit 862, Université Bordeaux Ségalen), Sarah Dubreucq, a PhD student and François Georges, a CNRS research leader at the Interdisciplinary Institute for Neuroscience (CNRS/Université Bordeaux Ségalen) have just discovered the key role played by a protein, the CB1 cannabinoid receptor, during physical exercise. In their mouse studies, the researchers demonstrated that the location of this receptor in a part of the brain associated with motivation and reward systems controls the time for which an individual will carry out voluntary physical exercise. These results were published in the journal Biological Psychiatry. 

The collective appraisal conducted by Inserm in 2008 highlighted the many preventive health benefits of regular physical activity. Such activity is limited, however, by our lifestyle in today’s industrial society. While varying degrees of physical inactivity may be partly explained by social causes, they are also rooted in biology.

“The inability to experience pleasure during physical activity, which is often quoted as one explanation why people partially or completely drop out of physical exercise programmes, is a clear sign that the biology of the nervous system is involved”, explains Francis Chaouloff.

But how exactly? The neurobiological mechanisms underlying physical inactivity had yet to be identified.

Francis Chaouloff (Giovanni Marsicano’s team at the NeuroCentre Magendie; Inserm joint research unit, Université Bordeaux Ségalen) and his team have now begun to decipher these mechanisms. Their work clearly identifies the endogenous cannabinoid (or endocannabinoid) system as playing a decisive role, in particular one of its brain receptors. This is by no means the first time that data has pointed to interactions between the endocannabinoid system, which is the target of delta9-tetrahydrocannabinol (the active ingredient of cannabis), and physical exercise. It was discovered ten years ago that physical exercise activated the endocannabinoid system in trained sportsmen, but its exact role remained a mystery for many years. Three years ago, the same research team in Bordeaux observed that when given the opportunity to use a running wheel, mutant mice lacking the CB1 cannabinoid receptor, which is the principal receptor of the endocannabinoid system in the brain, ran for a shorter time and over shorter distances than healthy mice. The research published in Biological Psychiatry this month seeks to understand how, where and why the lack of CB1 receptor reduces voluntary exercise performance (by 20 to 30%) in mice allowed access to a running wheel three hours per day.The researchers used various lines of mutant mice for the CB1 receptor, together with pharmacological tools. They began by demonstrating that the CB1 receptor controlling running performance is located at the GABAergic nerve endings. They went on to show that the receptor is located in the ventral tegmental area of the brain (see diagram below), which is an area involved in motivational processes relating to reward, whether the reward is natural (food, sex) or associated with the consumption of psychoactive substances.

 VTA: Ventral tegmental area/NAcc: nucleus accumbens/PFC: prefrontal cortex/DA: dopamine 

Based on the results of this study and earlier work, the Bordeaux team suggests the following neurobiological explanation: at the beginning and for the duration of physical exercise, the CB1 receptor is constantly simulated by the endocannabinoids, lipid molecules that naturally activate this receptor in response to pleasant stimuli (rewards) and unpleasant stimuli (stress). Endocannabinoid stimulation of the CB1 receptor during physical exercise inhibits the release of GABA, an inhibitory neurotransmitter that controls the activity of the dopamine neurons associated with the motivation and reward processes. This stimulation of the CB1 receptor “inhibits inhibition”, in other words, it activates the dopaminergic neurons in the ventral tegmental area. The CB1 receptor must therefore be stimulated before the exercise can go on for longer and the body must receive the necessary motivation.Conversely, without these CB1 receptors, the “GABAergic brake” continues to act on the dopaminergic neurons in the ventral tegmental area, leading to the reduced performance levels observed above.It is already known that CB1 receptors play a regulatory role in the motivation to consume rewards, whether natural or not. What is original about this research is that it shows that physical exercise can be added to the array of natural rewards regulated by the endocannabinoid system. “If confirmed, this motivational hypothesis would imply that the role played by the CB1 receptor has more to do with ‘staying power’ in the exercise than with actual physical performance levels” explain the researchers.

This work reveals that the endocannabinoid system plays a major role in physical exercise performance through its impact on motivational processes. It thus opens up new avenues of research into the mediators of pleasure – and even addiction – associated with regular physical exercise. “After endorphins, we now need to consider endocannabinoids as another potential mediator of the positive effects that physical exercise has on our mood,” the researchers conclude.

Source:Press Release Institute Thematiques

UCSB researchers perform pioneering research on Type 2 diabetes

While legions of medical researchers have been looking to understand the genetic basis of disease and how mutations may affect human health, a group of biomedical researchers at UC Santa Barbara is studying the metabolism of cells and their surrounding tissue, to ferret out ways in which certain diseases begin. This approach, which includes computer modeling, can be applied to Type 2 diabetes, autoimmune diseases, and neurodegenerative diseases, among others.
Scientists at UCSB have published groundbreaking results of a study of Type 2 diabetes that point to changes in cellular metabolism as the triggering factor for the disease, rather than genetic predisposition. Type 2 diabetes is a chronic condition in which blood sugar or glucose levels are high. It affects a large and growing segment of the human population, especially among the obese. The team of scientists expects the discovery to become a basis for efforts to prevent and cure this disease.

		This is Frank Doyle. Click here for more information.

The current work is based on a previous major finding by UCSB's Jamey Marth, who determined the identity of the molecular building blocks needed in constructing the four types of macromolecules of all cells when he was based at the Howard Hughes Medical Institute in La Jolla in 2008. These include the innate, genetic macromolecules, such as nucleic acids (DNA and RNA) and their encoded proteins, and the acquired metabolic macromolecules known as glycans and lipids. Marth is a professor in the Department of Molecular, Cellular, and Developmental Biology and the Biomolecular Science and Engineering Program; and holds the John Carbon Chair in Biochemistry and Molecular Biology and the Duncan and Suzanne Mellichamp Chair in Systems Biology. He is also a professor with the Sanford-Burnham Medical Research Institute in La Jolla.
"By studying the four types of components that make up the cell, we can, for the first time, begin to understand what causes many of the common grievous diseases that exist in the absence of definable genetic variation, but, instead, are due to environmental and metabolic alterations of our cells," said Marth. UCSB is the only institution studying these four types of molecules in the cells while also using computational modeling to determine their functions in health and disease, according to Marth.
The new study, published in the December 27 issue of PLOS ONE, relies on computational systems biology modeling to understand the pathogenesis of Type 2 diabetes.
"Even in the post-genomic era, after the human genome has been sequenced, we're beginning to realize that diseases aren't always in our genes –– that the environment is playing a major role in many of the common diseases," said Marth.

		This image shows four types of macromolecules in cells. The nucleic acids DNA and RNA and proteins are on the left and glycans and lipids are on the right. Click here for more information.

Normally, beta cells in the pancreas sense a rise in blood sugar and then secrete insulin to regulate blood glucose levels. But in Type 2 diabetes, the beta cells fail to execute this important function and blood sugar rises, a trend that can reach life-threatening levels. The researchers identified a "tipping point," or metabolic threshold, that when crossed results in the failure of beta cells to adequately sense glucose in order to properly secrete insulin.
Obesity has long been linked to Type 2 diabetes, but the cellular origin of the disease due to beta cell failure has not been described until now. "In obesity there's a lot of fat in the system," said Marth. "When the cell is exposed to high levels of fat or lipids, this mechanism starts, and that's how environment plays a role, among large segments of the population bearing 'normal' genetic variation. We're trying to understand what actually causes disease, which is defined as cellular dysfunction. Once we understand what causes disease we can make a difference by devising more rational and effective preventative and therapeutic approaches."
The research was based on a unique approach. "This project illustrates the power of systems biology; namely, how a network perspective combined with computational modeling can shed new light on biophysical circuits, such as this beta-cell glucose transport system," said co-author Frank Doyle. "It cannot be done by molecular biology alone, nor computational modeling alone; rather, it requires the uniquely interdisciplinary approach that is second-nature here at UCSB." Doyle is associate dean for research of the College of Engineering; director of UCSB's Institute for Collaborative Biotechnologies; professor of chemical engineering; and the Mellichamp Chair in Process Control.
"We are excited to bring our 20 years of expertise on Type 1 diabetes and systems biology methods to look at the networks responsible for the onset of Type 2 diabetes," said Doyle.
According to the American Diabetes Association, 8.3 percent of the U.S. population has diabetes. The disease can lead to nerve loss, blindness, and death.
The first author of the paper is Camilla Luni, who was a UCSB postdoctoral researcher at the time of the study, and is now with the University of Padova, in Italy. The research was funded by a grant from the U.S. Army Research Office to UCSB's Institute for Collaborative Biotechnologies, and a grant from the U.S. National Institutes of Health.
Source:University of California - Santa Barbara 

 

How prostate cancer therapies compare by cost and effectiveness

Surgery ranks as the most cost-effective type of treatment, according to UCSF-led study

		This is Matthew Cooperberg, M.D., M.P.H. Click here for more information.

The most comprehensive retrospective study ever conducted comparing how the major types of prostate cancer treatments stack up to each other in terms of saving lives and cost effectiveness is reported this week by a team of researchers at the University of California, San Francisco (UCSF).
Appearing in the British Journal of Urology International, the work analyzed 232 papers published in the last decade that report results from clinical studies following patients with low-, intermediate- and high-risk forms of prostate cancer who were treated with one or more of the standard treatments – radiation therapy, surgery, hormone therapies and brachytherapy.
The analysis shows that for people with low-risk prostate cancer, the various forms of treatment vary only slightly in terms of survival – the odds of which are quite good for men with this type of cancer, with a 5-year cancer-specific survival rate of nearly 100 percent. But the cost of radiation therapy is significantly more expensive than surgery for low-risk prostate cancer, they found.
For intermediate- and high-risk cancers, both survival and cost generally favored surgery over other forms of treatment – although combination external-beam radiation and brachytherapy together were comparable in terms of quality of life-adjusted survival for high-risk prostate cancer.
"Our findings support a greater role for surgery for high-risk disease than we have generally seen it used in most practice settings," said urologist Matthew Cooperberg, MD, MPH who led the research. Cooperberg is an assistant professor of urology and epidemiology and biostatistics in the UCSF Helen Diller Family Comprehensive Cancer Center.
The UCSF Helen Diller Family Comprehensive Cancer Center is one of the country's leading research and clinical care centers, and it is the only comprehensive cancer center in the San Francisco Bay Area.
Many Treatment Options, but Few Cost Analyses
Localized prostate cancer accounts for about 81 percent of the quarter-million cases of prostate cancers that occur in the United States every year, according to the National Cancer Institute. It is defined by tumors that have not metastasized and spread outside the prostate gland to other parts of the body.
There are multiple types of treatment for this form of the disease, including various types of surgery (open, laparoscopic or robot-assisted); radiation therapy (dose-escalated three-dimensional conformal radiation therapy, intensity-modulated radiation therapy and brachytherapy); hormone therapies; and combinations of each of these. Many men with low-risk prostate cancer do not need any of these treatments, and can be safely observed, at least initially.
Treatment plans for localized prostate cancer often vary dramatically from one treatment center to another. As Cooperberg put it, one person may have surgery, while someone across town with a very similar tumor may have radiation therapy, and a third may undergo active surveillance. All treatment regimens may do equally well.
"There is very little solid evidence that one [approach] is better than another," said Cooperberg. The motivation for the new study, however, was that there are also few data examining the differences in terms of cost-effectiveness – the price to the health care system for every year of life gained, with adjustment for complications and side effects of treatments.
The new study was the most comprehensive cost analysis ever, and it compared the costs and outcomes associated with the various types of treatment for all forms of the disease, which ranged from $19,901 for robot-assisted prostatectomy to treat low-risk disease, to $50,276 for combined radiation therapy for high-risk disease.
The study did not consider two other approaches for dealing with prostate cancer: active surveillance, where patients with low-risk cancer are followed closely with blood tests and biopsies and avoid any initial treatment; and proton therapy, which is much more expensive and has already been shown in multiple studies not to be cost-effective, said Cooperberg.
Source:University of California - San Francisco