Scientists identify signature of aging in the brain

An immunofluorescence microscope image of the choroid plexus. Epithelial cells are in green and chemokine proteins (CXCL10) are in red Credit: Weizmann Institute of Science

30 sept 2014--How the brain ages is still largely an open question – in part because this organ is mostly insulated from direct contact with other systems in the body, including the blood and immune systems. In research that was recently published in Science, Weizmann Institute researchers Prof. Michal Schwartz of the Neurobiology Department and Dr. Ido Amit of Immunology Department found evidence of a unique "signature" that may be the "missing link" between cognitive decline and aging. The scientists believe that this discovery may lead, in the future, to treatments that can slow or reverse cognitive decline in older people.

Until a decade ago, scientific dogma held that the blood-brain barrier prevents the blood-borne immune cells from attacking and destroying brain tissue. Yet in a long series of studies, Schwartz's group had shown that the immune system actually plays an important role both in healing the brain after injury and in maintaining the brain's normal functioning. They have found that this brain-immune interaction occurs across a barrier that is actually a unique interface within the brain's territory.

This interface, known as the choroid plexus, is found in each of the brain's four ventricles, and it separates the blood from the cerebrospinal fluid. Schwartz: "The choroid plexus acts as a 'remote control' for the immune system to affect brain activity. Biochemical 'danger' signals released from the brain are sensed through this interface; in turn, blood-borne immune cells assist by communicating with the choroid plexus. This cross-talk is important for preserving cognitive abilities and promoting the generation of new brain cells." This finding led Schwartz and her group to suggest that cognitive decline over the years may be connected not only to one's "chronological age" but also to one's "immunological age," that is, changes in immune function over time might contribute to changes in brain function – not necessarily in step with the count of one's years.

To test this theory, Schwartz and research students Kuti Baruch and Aleksandra Deczkowska teamed up with Amit and his research group in the Immunology Department. The researchers used next-generation sequencing technology to map changes in gene expression in 11 different organs, including the choroid plexus, in both young and aged mice, to identify and compare pathways involved in the aging process. That is how they identified a strikingly unique "signature of aging" that exists solely in the choroid plexus – not in the other organs. They discovered that one of the main elements of this signature was interferon beta – a protein that the body normally produces to fight viral infection. This protein appears to have a negative effect on the brain: When the researchers injected an antibody that blocks interferon beta activity into the cerebrospinal fluid of the older mice, their cognitive abilities were restored, as was their ability to form new brain cells. The scientists were also able to identify this unique signature in elderly human brains. The scientists hope that this finding may, in the future, help prevent or reverse cognitive decline in old age, by finding ways to rejuvenate the "immunological age" of the brain.

More information: Science, www.sciencemag.org/content/ear… science.1252945.full

Provided by Weizmann Institute of Science

Think you have Alzheimer's? You just might be right, study says

Diagram of the brain of a person with Alzheimer's Disease. Credit: Wikipedia/public domain.

New research by scientists at the University of Kentucky's Sanders-Brown Center on Aging suggests that people who notice their memory is slipping may be on to something.

29 sept 2014--The research, led by Richard Kryscio, PhD, Chairman of the Department of of Biostatistics and Associate Director of the Alzheimer's Disease Center at the University of Kentucky, appears to confirm that self-reported memory complaints are strong predictors of clinical memory impairment later in life.

Kryscio and his group asked 531 people with an average age of 73 and free of dementia if they had noticed any changes in their memory in the prior year. The participants were also given annual memory and thinking tests for an average of 10 years. After death, participants' brains were examined for evidence of Alzheimer's disease.

During the study, 56 percent of the participants reported changes in their memory, at an average age of 82. The study found that participants who reported changes in their memory were nearly three times more likely to develop memory and thinking problems. About one in six participants developed dementia during the study, and 80 percent of those first reported memory changes.

"What's notable about our study is the time it took for the transition from self-reported memory complaint to dementia or clinical impairment—about 12 years for dementia and nine years for clinical impairment—after the memory complaints began," Kryscio said. "That suggests that there may be a significant window of opportunity for intervention before a diagnosable problem shows up."

Kryscio points out that while these findings add to a growing body of evidence that self-reported memory complaints can be predictive of cognitive impairment later in life, there isn't cause for immediate alarm if you can't remember where you left your keys.

"Certainly, someone with memory issues should report it to their doctor so they can be followed. Unfortunately, however, we do not yet have preventative therapies for Alzheimer's disease or other illnesses that cause memory problems."

More information: The research was published in the September 24th, 2014 online issue of Neurology.

Provided by University of Kentucky

Talk therapy—not medication—best for social anxiety disorder, large study finds

While antidepressants are the most commonly used treatment for social anxiety disorder, new research suggests that cognitive behavioral therapy (CBT) is more effective and, unlike medication, can have lasting effects long after treatment has stopped.

28 sept 2014--Social anxiety disorder is a psychiatric condition characterized by intense fear and avoidance of social situations and affects up to 13 percent of Americans and Europeans. Most people never receive treatment for the disorder. For those who do, medication is the more accessible treatment because there is a shortage of trained psychotherapists.

The findings of the study, a network meta-analysis that collected and analyzed data from 101 clinical trials comparing multiple types of medication and talk therapy, are published online Sept. 26 in The Lancet Psychiatry.

"Social anxiety is more than just shyness," says study leader Evan Mayo-Wilson, DPhil, a research scientist in the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health. "People with this disorder can experience severe impairment, from shunning friendships to turning down promotions at work that would require increased social interaction. The good news from our study is that social anxiety is treatable. Now that we know what works best, we need to improve access to psychotherapy for those who are suffering."

The research was a collaboration between the Johns Hopkins Bloomberg School of Public Health, Oxford University and University College in London, where Mayo-Wilson formerly worked.

For the study, Mayo-Wilson and his colleagues analyzed data from 13,164 participants in 101 clinical trials. The participants all had severe and longstanding social anxiety.

Approximately 9,000 received medication or a placebo pill, and more than 4,000 received a psychological intervention.

Few of the trials looked at combining medication with talk therapy, and there was no evidence that combined therapy was better than talk therapy alone.

The data compared several different types of talk therapy and found individual CBT was the most effective. CBT is a form of treatment that focuses on relationships between thoughts, feelings and behaviors. It helps people challenge irrational fears and overcome their avoidance of social situations, Mayo-Wilson says.

For people who don't want talk therapy, or who lack access to CBT, the most commonly used antidepressants—selective serotonin reuptake inhibitors (SSRIs)—are effective, the researchers found. But they caution that medication can be associated with serious adverse events, that it doesn't work at all for many people, and that improvements in symptoms do not last after people stop taking the pills.

The researchers acknowledge that medication remains important but say it should be used as a second-line therapy for people who do not respond to or do not want psychological therapy. The group's analysis has already led to new treatment guidelines guidance in the U.K. and, Mayo-Wilson says, it could have a significant impact on policymaking and the organization of care in the U.S.

Social anxiety disorder typically begins in adolescence or early adulthood, and it can severely impair a person's daily functioning by impeding the formation of relationships, by negatively affecting performance at work or school, and by reducing overall quality of life. Because it strikes people at critical times in their social and educational development, social anxiety disorder can have important and lasting consequences.

"Greater investment in psychological therapies would improve quality of life, increase workplace productivity, and reduce healthcare costs," Mayo-Wilson says. "The healthcare system does not treat mental health equitably, but meeting demand isn't simply a matter of getting insurers to pay for psychological services. We need to improve infrastructure to treat mental health problems as the evidence shows they should be treated. We need more programs to train clinicians, more experienced supervisors who can work with new practitioners, more offices, and more support staff."

More information: "Psychological and Pharmacological Interventions for Social Anxiety Disorder in Adults: A Systematic Review and Network Meta-Analysis," The Lancet Psychiatry, 2014.

Provided by Johns Hopkins University Bloomberg School of Public Health

One in ten people over forty years old in Britain is vitamin D deficient

Vitamin D. Credit: Collin Grady via flickr

As many as one in ten people in Britain over forty years old may be vitamin D deficient, according to a study carried out by researchers at the University of Cambridge.

27 sept 2014--Vitamin D is nicknamed the 'sunshine vitamin' as it is produced in the skin in response to sunlight. It is also found in some foods, such as oily fish (including salmon and mackerel) and eggs. Low levels of the vitamin have been associated with increased risk of conditions as wide-ranging as rickets, bone fractures, diabetes, respiratory diseases and cancers. People living in northern Europe, where sunlight is often insufficient to manufacture adequate vitamin D, have to rely on body stores of vitamin D produced over the summer months.

In a study funded by the Medical Research Council and Cancer Research UK, Cambridge researchers looked at levels of vitamin D in blood samples taken from around 15,000 participants from the European Prospective Investigation into Cancer (EPIC) in Norfolk Study in order to identify optimal levels of the vitamin for health.

"We know that vitamin D deficiency can be detrimental to health, but until now there has been no clear answer as to what is actually the ideal amount of the vitamin," explains Professor Nick Wareham, Director of the Medical Research Council Epidemiology Unit at the University of Cambridge. "Outside of those whose levels are extremely low, we've had no way of knowing how many people are actually getting less vitamin D than they need."

Trials involving vitamin D supplements have so far proved inconclusive, possibly because the method in which the vitamin D is administered (orally or intramuscularly), the type of vitamin D (D3 or D2) and frequency and amount have differed between trials, and hence blood levels and biological effects vary hugely.

The Cambridge team measured the amount of 25-hydroxyvitamin D in the blood, which is an indicator of individual vitamin D status. Previous studies have suggested that individuals with less than 30 nanomoles per litre (nmol/l) of the molecule are at risk of rickets and other bone diseases, but that too much vitamin D – over 125 nmol/l – could potentially be detrimental to one's health.

By comparing blood levels of 25-hydroxyvitamin D with health of individuals over the next 13 years the researchers found that between 30 and 120 nmol/l, the higher the amount of the molecule in an individual's blood, the lower their risk of heart disease, respiratory diseases and bone fractures. In fact, for every additional 20 nmol/l, an individual had an 8% smaller chance of dying during the 13 year follow up. Only one per cent of the participants had levels above 120 nmol/l, so it was not possible to say what effect higher levels of vitamin D had on an individual's health.

The researchers suggest that the optimum level of 25-hydroxyvitamin D in the blood is somewhere between 50-90 nmol/l. Over four in ten of the 15,000 individuals studied fell below this level.

"Our data suggest that a modest increase in vitamin D in the general population may minimise the number of people with very low levels of the vitamin and may have some benefits even for those whose levels are acceptable," adds Professor Kay-Tee Khaw from the Department of Public Health and Primary Care, University of Cambridge.

"This could be achieved by taking modest daily vitamin D supplements—around 800IU daily—or eating oily fish two or three times a week and increasing physical activity as we are more efficient at producing vitamin D if we are physically active. We only need around 20 minutes a day of sunlight in summer to ensure that we have sufficient levels to see us through the winter and must be careful as we know that over-exposure to sunlight – particularly if we burn – raises skin cancer risk."

More information: The complete study is available online: ajcn.nutrition.org/content/ear… 086413.full.pdf+html

Provided by University of Cambridge

Alzheimer's patients can still feel the emotion long after the memories have vanished

Jade Angelica, founder and director of Healing Moments Alzheimer’s Ministry in Dubuque, Iowa, considers caring for her mother, Jeanne, to be the most important work of her life. Jade’s mother died from Alzheimer’s in 2011. Jade is author of the book "Where Two Worlds Touch: A Spiritual Journey Through Alzheimer's Disease." Edmarie Guzman-Velez and her colleagues reference Jade’s book in their research paper, “Feelings Without Memory in Alzheimer Disease” published in the journal Cognitive and Behavioral Neurology. Credit: Jade Angelica.

A new University of Iowa study further supports an inescapable message: caregivers have a profound influence—good or bad—on the emotional state of individuals with Alzheimer's disease. Patients may not remember a recent visit by a loved one or having been neglected by staff at a nursing home, but those actions can have a lasting impact on how they feel.

26 sept 2014--The findings of this study are published in the September 2014 issue of the journal Cognitive and Behavioral Neurology, and can be viewed online for free here.

UI researchers showed individuals with Alzheimer's disease clips of sad and happy movies. The patients experienced sustained states of sadness and happiness despite not being able to remember the movies.

"This confirms that the emotional life of an Alzheimer's patient is alive and well," says lead author Edmarie Guzmán-Vélez, a doctoral student in clinical psychology, a Dean's Graduate Research Fellow, and a National Science Foundation Graduate Research Fellow.

Guzmán-Vélez conducted the study with Daniel Tranel, UI professor of neurology and psychology, and Justin Feinstein, assistant professor at the University of Tulsa and the Laureate Institute for Brain Research.

Tranel and Feinstein published a paper in 2010 that predicted the importance of attending to the emotional needs of people with Alzheimer's, which is expected to affect as many as 16 million people in the United States by 2050 and cost an estimated $1.2 trillion.

"It's extremely important to see data that support our previous prediction," Tranel says. "Edmarie's research has immediate implications for how we treat patients and how we teach caregivers."

This is a coronal view of the hippocampus brain region of a patient with Alzheimer’s disease. Credit: Daniel Tranel's Laboratory at the UI's Department of Neurology.

Despite the considerable amount of research aimed at finding new treatments for Alzheimer's, no drug has succeeded at either preventing or substantially influencing the disease's progression. Against this foreboding backdrop, the results of this study highlight the need to develop new caregiving techniques aimed at improving the well-being and minimizing the suffering for the millions of individuals afflicted with Alzheimer's.

For this behavioral study, Guzmán-Vélez and her colleagues invited 17 patients with Alzheimer's disease and 17 healthy comparison participants to view 20 minutes of sad and then happy movies. These movie clips triggered the expected emotion: sorrow and tears during the sad films and laughter during the happy ones.

About five minutes after watching the movies, the researchers gave participants a memory test to see if they could recall what they had just seen. As expected, the patients with Alzheimer's disease retained significantly less information about both the sad and happy films than the healthy people. In fact, four patients were unable to recall any factual information about the films, and one patient didn't even remember watching any movies.

Before and after seeing the films, participants answered questions to gauge their feelings. Patients with Alzheimer's disease reported elevated levels of either sadness or happiness for up to 30 minutes after viewing the films despite having little or no recollection of the movies.

Quite strikingly, the less the patients remembered about the films, the longer their sadness lasted. While sadness tended to last a little longer than happiness, both emotions far outlasted the memory of the films.

The fact that forgotten events can continue to exert a profound influence on a patient's emotional life highlights the need for caregivers to avoid causing negative feelings and to try to induce positive feelings.

"Our findings should empower caregivers by showing them that their actions toward patients really do matter," Guzmán-Vélez says. "Frequent visits and social interactions, exercise, music, dance, jokes, and serving patients their favorite foods are all simple things that can have a lasting emotional impact on a patient's quality of life and subjective well-being."

Provided by University of Iowa

The plus side of population aging

Around the world, people are living longer and having fewer children, leading to a population that is older, on average, than in the past. On average, life expectancy in developed countries has risen at a pace of three months per year, and fertility has fallen below replacement rate in the majority of Europe and other developed countries.

25 sept 2014--Most academic discussion of this trend has so far focused on potential problems it creates, including challenges to pension systems, economic growth, and healthcare costs.

But according to a new study published today in the journal PLOS ONE, population aging and the compositional change that go along with it—such as increasing education levels—may turn out to have many positive impacts for society.

"In order to give a more complete picture of population aging, it is necessary to include both positive and negative effects of population aging," says IIASA researcher Elke Loichinger, who wrote the article in collaboration with researchers from the Max Planck Institute in Rostock, Germany, and the University of Washington.

The researchers chose to use Germany as a case study because the country is at an advanced stage of the demographic transition, with a current fertility rate of around 1.4 and the second oldest average population in the world (median age 44.3 years). They identified five areas in which population aging could bring net benefits, when considered in combination with other demographic factors:

• Increased productivity: While population aging will likely lead to a decline in the labor force, expected increases in workers' education levels can partly compensate for this decline through higher productivity.
• Aging could be good for the environment: Changes in the age structure and a declining population size are associated with reduced consumption of energy-intensive goods and lower carbon dioxide emissions.
• Sharing wealth with the younger generations: As life expectancy increases, people would inherit, on average, at older ages and potentially use some of the inheritance to either fund their retirement or help their children financially as they become adults. Moreover, as families have fewer children, inheritance will be split between fewer people, so that, all else being constant, individuals would receive more on average.
• Health: As people live longer, they also stay healthier longer. The results project that the average German man in 2050 will spend 80% of his lifetime in good health, compared to 63% today.
• Quality of life: The study suggests that the relationship between leisure, work, and housework will change in the future, with leisure time increasing on average.

While the study focused on Germany, the researchers say that the findings are applicable across many aging societies. Loichinger says, "The particular context of another country will determine the degree of their relevance. For example, an increase in educational attainment levels can be found almost universally around the globe, and the finding that the elderly belonging to subsequent cohorts have better health has also been shown in other contexts. Depending on a country's stage in the demographic transition process, the results from the analyses of bequests and CO2 emissions are also generalizable."

The study provides a new perspective at a time when population aging is spreading to many countries around the world. Loichinger says, "The extent of population aging that is going on and expected is beyond what has ever been observed before. Since there is no precedent to this development, there is also no blueprint how to deal with it."

More information: Kluge F, Zagheni E, Loichinger E, Vogt T. 2014. The advantages of demographic change after the wave: Fewer and older but healthier, greener, and more productive? PLOS ONE.

Provided by International Institute for Applied Systems Analysis

Healthy lifestyle choices may dramatically reduce risk of heart attack in men

Myocardial Infarction or Heart Attack. Credit: Blausen Medical Communications/Wikipedia/CC-A 3.0

Following a healthy lifestyle, including maintaining a healthy weight and diet, exercise, not smoking and moderating alcohol intake, could prevent four out of five coronary events in men, according to a new study publishing today in the Journal of the American College of Cardiology.

24 sept 2014--While mortality from heart disease has declined in recent decades, with much of the reduction attributed to medical therapies, the authors said prevention through a healthy lifestyle avoids potential side effects of medication and is more cost effective for population-wide reductions in coronary heart disease.

For the study, researchers examined a population of 20,721 healthy Swedish men aged 45-79 years of age and followed them for 11 years. Lifestyle choices were assessed through a questionnaire exploring diet, alcohol consumption, smoking status, level of physical activity and abdominal adiposity (belly fat). Men in the study with the lowest risk were non-smokers, walked or cycled for at least 40 minutes per day, exercised at least one hour per week, had a waist circumference below 95 centimeters, consumed moderate amounts of alcohol, and followed a healthy diet with a regular consumption of fruits, vegetables, legumes, nuts, reduced-fat dairy products, whole grains and fish.

The researchers found a clear reduction in risk for heart attack for each individual lifestyle factor the participants practiced. For instance having a low-risk diet together with a moderate alcohol consumption led to an estimated 35 percent lower risk of heart attack compared to the high-risk group, those who practice none of the low-risk factors.

Men who combined the low-risk diet and moderate alcohol consumption with not smoking, being physically active and having a low amount of abdominal fat, had 86 percent lower risk. Researchers found similar results in men with hypertension andhigh cholesterol levels.

"It is not surprising that healthy lifestyle choices would lead to a reduction in heart attacks," said Agneta Akesson, Ph.D., Associate Professor at the Institute of Environmental Medicine, Karolinska Institutet, Stockholm, and lead author of the study. "What is surprising is how drastically the risk dropped due to these factors."

According to the authors, less than 2 percent of the American population conforms to what is defined as ideal cardiovascular health. The burden of cardiovascular disease could be significantly reduced through programs targeted to men and promoting low-risk lifestyle choices. Even in those who take medication, an additional reduction in risk for chronic heart disease has been observed in those with a healthy lifestyle.

"It is important to note that these lifestyle behaviors are modifiable, and changing from high-risk to low-risk behaviors can have great impact on cardiovascular health," Akesson said. "However, the best thing one can do is to adopt healthy lifestyle choices early in life."

Provided by American College of Cardiology

Platelets modulate clotting behavior by 'feeling' their surroundings

Researchers devised a way to separate the physical stiffness of the material where platelets spread out from its biochemical properties. Credit: Wilbur Lam

Platelets, the tiny cell fragments whose job it is to stop bleeding, are very simple. They don't have a cell nucleus. But they can "feel" the physical environment around them, researchers at Emory and Georgia Tech have discovered.

23 sept 2014--Platelets respond to surfaces with greater stiffness by increasing their stickiness, the degree to which they "turn on" other platelets and other components of the clotting system, the researchers found.

"Platelets are smarter than we give them credit for, in that they are able to sense the physical characteristics of their environment and respond in a graduated way," says Wilbur Lam, MD, PhD, assistant professor in the Department of Pediatrics at Emory University School of Medicine and in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

The results are published in Proceedings of the National Academy of Sciences. The first author of the paper is research associate Yongzhi Qiu. Lam is also a physician in the Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta.

The researchers' findings could influence the design of medical devices, because when platelets grab onto the surfaces of catheters and medical implants, they tend to form clots, a major problem for patient care.

Modifying the stiffness of materials used in these devices could reduce clot formation, the authors suggest. The results could also guide the refinement of blood thinning drugs, which are prescribed to millions to reduce the risk of heart attack or stroke.

The team was able to separate physical and biochemical effects on platelet behavior by forming polymer gels with different degrees of stiffness, and then overlaying them each with the same coating of fibrinogen, a sticky protein critical for blood clotting. Fibrinogen is the precursor for fibrin, which forms a mesh of insoluble strands in a blood clot.

With stiffer gels, platelets spread out more and become more activated. This behavior is most pronounced when the concentration of fibrinogen is relatively low, the researchers found.

"This variability helps to explain platelet behavior in the 3D context of a clot in the body, which can be quite heterogenous in makeup," Lam says.

Qiu and colleagues were also able to dissect platelet biochemistry by allowing the platelets to adhere and then spread on the various gels under the influence of drugs that interfere with different biochemical steps.

Proteins called integrins, which engage the fibrinogen, and the protein Rac1 are involved in the initial mechanical sensing during adhesion, while myosin and actin, components of the cytoskeleton, are responsible for platelet spreading.

"We found that the initial adhesion and later spreading are separable, because different biochemical pathways are involved in each step," Lam says. "Our data show that mechanosensing can occur and plays important roles even when the cellular structural building blocks are fairly basic, even when the nucleus is absent."

More information: Platelet mechanosensing of substrate stiffness during clot formation mediates adhesion, spreading, and activation, PNAS,www.pnas.org/cgi/doi/10.1073/pnas.1322917111

Provided by Emory University

A positive boost to the immune system

A positive attitude can boost your immune system and help you live longer. Credit: iStock

22 sept 2014—A positive attitude can improve your immune system and may help you live longer, according to a University of Queensland study.

The research, published in Psychology and Aging has found that older people who focused on positive information were more likely to have stronger immune systems.

Lead researcher Dr Elise Kalokerinos, from UQ's School of Psychology, said a positive attitude played an important role in healthy ageing.

"Despite the fact that people often think of late life as a period of doom and gloom, older people are often more positive than younger people," Dr Kalokerinos said.

"Our research suggests that this focus on the positive may help older people protect their declining health."

The study involved following 50 adults, aged 65-90 years, across two years.

Participants were shown a series of positive and negative photos, which they were later asked to recall, and their immune function was also measured through a series of blood tests.

Dr Kalokerinos said participants who remembered more positive than negative images also showed better immune functioning up to two years later.

"Participants who recalled more positive than negative images had antibodies in their blood suggesting stronger immune systems than those of their counterparts, who did not show this positivity in memory," she said.

"By selectively remembering the positive, older adults seem to boost their immune functioning just when they need it the most.

"We already know that happiness provides a range of health benefits and this research shows that focusing on positive information may have the same effect for older people.

"A person who focuses on positive information over negative information may be better able to cope with stressful situations, may take a more positive long-term outlook on life, and may maintain positive social interactions, thus reaping the immune benefits.

"These findings raise the possibility that humans have evolved to become more positive late in life in order to enhance their own longevity."

Provided by University of Queensland

Scientists discover an on/off switch for aging cells

Victoria Lundblad and Timothy Tucey. Credit: Salk Institute for Biological Studies

21 sept 2014—Scientists at the Salk Institute have discovered an on-and-off "switch" in cells that may hold the key to healthy aging. This switch points to a way to encourage healthy cells to keep dividing and generating, for example, new lung or liver tissue, even in old age.

In our bodies, newly divided cells constantly replenish lungs, skin, liver and other organs. However, most human cells cannot divide indefinitely–with each division, a cellular timekeeper at the ends of chromosomes shortens. When this timekeeper, called a telomere, becomes too short, cells can no longer divide, causing organs and tissues to degenerate, as often happens in old age. But there is a way around this countdown: some cells produce an enzyme called telomerase, which rebuilds telomeres and allows cells to divide indefinitely.

In a new study published September 19th in the journal Genes and Development, scientists at the Salk Institute have discovered that telomerase, even when present, can be turned off.

"Previous studies had suggested that once assembled, telomerase is available whenever it is needed," says senior author Vicki Lundblad, professor and holder of Salk's Ralph S. and Becky O'Connor Chair. "We were surprised to discover instead that telomerase has what is in essence an 'off' switch, whereby it disassembles."

Understanding how this "off" switch can be manipulated–thereby slowing down the telomere shortening process–could lead to treatments for diseases of aging (for example, regenerating vital organs later in life).

Lundblad and first author and graduate student Timothy Tucey conducted their studies in the yeast Saccharomyces cerevisiae, the same yeast used to make wine and bread. Previously, Lundblad's group used this simple single-celled organism to reveal numerous insights about telomerase and lay the groundwork for guiding similar findings in human cells.

"We wanted to be able to study each component of the telomerase complex but that turned out to not be a simple task," Tucey said. Tucey developed a strategy that allowed him to observe each component during cell growth and division at very high resolution, leading to an unanticipated set of discoveries into how–and when–this telomere-dedicated machine puts itself together.

Every time a cell divides, its entire genome must be duplicated. While this duplication is going on, Tucey discovered that telomerase sits poised as a "preassembly" complex, missing a critical molecular subunit. But when the genome has been fully duplicated, the missing subunit joins its companions to form a complete, fully active telomerase complex, at which point telomerase can replenish the ends of eroding chromosomes and ensure robust cell division.

Surprisingly, however, Tucey and Lundblad showed that immediately after the full telomerase complex has been assembled, it rapidly disassembles to form an inactive "disassembly" complex—essentially flipping the switch into the "off" position. They speculate that this disassembly pathway may provide a means of keeping telomerase at exceptionally low levels inside the cell. Although eroding telomeres in normal cells can contribute to the aging process, cancer cells, in contrast, rely on elevated telomerase levels to ensure unregulated cell growth. The "off" switch discovered by Tucey and Lundblad may help keep telomerase activity below this threshold.

More information: Genes and Development, genesdev.cshlp.org/content/ear… .246256.114.abstract

Provided by Salk Institute

Patients with advanced, incurable cancer denied palliative care

Many patients with advanced, incurable cancer do not receive any palliative care, reveals new research to be presented later this month at the ESMO 2014 Congress in Madrid, Spain, 26-30 September. The findings are astonishing as they come at the same time as 15 new oncology centres in Europe, Canada, South America and Africa are being awarded the prestigious title of 'ESMO Designated Centre of Integrated Oncology and Palliative Care.'

20 sept 2014--SR I Dr Alexandru Grigorescu, medical oncology consultant at the Institute of Oncology Bucharest, Romania, member of the ESMO Palliative Care Working Group, said: "The integration of palliative care in oncology is a challenge. This is especially the case for countries with few resources, where the healthcare budget is low, with insufficient palliative care specialists and some drugs are unavailable as hospitals do not have the funds to buy them."

"ESMO brings a new approach to palliative care, namely by integrating it with specific anticancer treatment conducted in medical oncology departments," continued Grigorescu. "In this context, we conducted a study to assess palliative care needs and delivery in patients with advanced, incurable cancer."1

The research was conducted in five Romanian and one Swiss institutes. It found that 17% of patients received no palliative care interventions and 26% did not have their symptoms addressed. One-fifth of patients wanted to discuss end-of-life issues with a healthcare professional, but it occurred in just 15% of cases. Only 10% of patients had a care plan.

Grigorescu said: "Our study shows that there are significant gaps in the delivery of palliative care for patients with advanced, incurable cancer. Our findings argue for healthcare decision-makers to increase the budget for palliative care. We hope the study will make a point about the importance of treating patients during this period. In Romania we do not have an independent speciality of palliative care, so it should be the responsibility of medical oncologists."

ESMO promotes good practice in palliative care for cancer patients through –among others— the ESMO Designated Centres of Integrated Oncology and Palliative Care accreditation programme.2 The designation recognises that centres have achieved a high standard of integration of medical oncology and palliative care and is valid for three years.

Prof Nathan Cherny, former chair of the ESMO Palliative Care Working Group and initiator of the Designated Centres programme, said: "The ESMO Designated Centres programme is the premier initiative worldwide for providing incentives and a structured model to enable centres to develop integrated programmes in oncology and palliative care. The ESMO designation is widely recognised and indicates that the centre has made philosophical and infrastructural commitments to meet the physical and psychological challenges of patients and families with advanced cancers."

Cherny, an oncologist and palliative medicine specialist who is chair of humanistic medicine at Shaare Zedek Medical Centre, Jerusalem, Israel, added: "The designation also indicates that the centre is not only providing a clinical service but that it has programmes developed both to push the boundaries of knowledge through research and to teach the essential skills required for the provision of palliative care to cancer patients."

Since the programme began in 2003, the Designated Centre accolade has been awarded to 175 centres, of which 25 are in resource and/or regulation restrictive countries. In addition to the 15 new centres joining the prestigious group this year, 44 centres have achieved reaccreditation.

Commenting on ESMO's activities in the field of palliative care, Cherny said: "ESMO has a 15 year history of a commitment to the improvement of the quality of palliative care for cancer patients in Europe and around the world. ESMO was the first major oncology organisation to develop a dedicated working group to this task, and to develop policies for individual clinicians, for cancer centres and for the training of oncologists. ESMO has researched its own membership to identify deficits in knowledge and practice and has developed educational tools to address the shortcomings that were identified."

ESMO has been a leading player in identifying barriers to the availability and accessibility of essential pain relieving medication in Europe and in the developing world. Cherny said: "The findings from the Global Opioid Policy Initiative (GOPI) study3have major policy implications that are relevant to over five billion of the world's population. We are working with our partners to promote legislative reforms to guarantee that all patients have access to affordable, effective pain medication to relieve the tragedy of needless suffering caused by undertreated cancer pain."

To promote better care for patients with advanced cancer ESMO published a guide for patients and their families4 and a companion volume for oncologists5. The ESMO Guidelines Working Group is developing evidence-based clinical practice guidelines to assist oncologists in the provision of palliative care. This month three new guidelines have been published.6 Cherny said: "Together these publications help patients with advanced and incurable cancer ask appropriate questions and have meaningful discussions with their oncologist that lead to coordinated and holistic care. The patient book has been translated into 11 languages and is an invaluable resource."

"With its strong commitment to research, best practice and palliative care, ESMO has become a key partner in palliative care initiatives," added Rolf A. Stahel, ESMO President.

Cherny concluded: "Palliative care has been a central part of ESMO's work in research, education and public health policy initiatives both in Europe and around the world. This year's new and reaccredited ESMO Designated Centres will ensure that more patients with cancer receive appropriate, high quality palliative care along with the best of their cancer care - and this makes a difference."

More information: 1 Abstract 1347P, Poster Display session, 28.09.2014, 12:45 - 13:45, Poster area

2 ESMO's Designated Centres programme: www.esmo.org/Patients/Designat… -and-Palliative-Care

3 ESMO Global Opioid Policy Initiative (GOPI): www.esmo.org/Policy/Global-Opi… id-Policy-Initiative

4 A guide for patients with advanced cancer: Getting the most out of your oncologist: www.esmo.org/Patients/Getting-… t-of-Your-Oncologist

5 User's manual for oncology clinicians: oncologypro.esmo.org/Publicati… -Oncology-Clinicians

6 ESMO Clinical Practice Guidelines for the management of refractory symptoms at the end of life and the use of palliative sedation. N. I. Cherny, on behalf of the ESMO Guidelines Working Group. Ann Oncol 2014 25: iii143-iii152.

ESMO Clinical Practice Guidelines on palliative care: advanced care planning. D. Schrijvers, N. I. Cherny, on behalf of the ESMO Guidelines Working Group. Ann Oncol 2014 25: iii138-iii142.

Bone health in cancer patients: ESMO Clinical Practice Guidelines. R. Coleman, J. J. Body, M. Aapro, P. Hadji, J. Herrstedt, on behalf of the ESMO Guidelines Working Group. Ann Oncol 2014 25: iii124-iii137.

Provided by European Society for Medical Oncology

How pneumonia bacteria can compromise heart health

Microlesions (indicated by circles) in the heart of a mouse 30 hours after induction of invasive pneumococcal disease. Credit: PLoS Pathogens, 2014

Bacterial pneumonia in adults carries an elevated risk for adverse cardiac events (such as heart failure, arrhythmias, and heart attacks) that contribute substantially to mortality—but how the heart is compromised has been unclear. A study published on September 18th in PLOS Pathogens now demonstrates that Streptococcus pneumoniae, the bacterium responsible for most cases of bacterial pneumonia, can invade the heart and cause the death of heart muscle cells.

19 sept 2014--Carlos Orihuela, from the University of Texas Health Science Center in San Antonio, USA, and colleagues initially studied the reasons for heart failure during invasive pneumococcal disease (when S. pneumoniae bacteria infect major organs such as the lungs, bloodstream, and brain) in mice, and subsequently confirmed some of their main findings in rhesus macaques and in heart tissue from deceased human patients.

Mice with severe invasive pneumococcal disease showed elevated levels of troponin, a marker for heart injury, in their blood. They also had abnormal EKGs. When the researchers examined the hearts of the mice, they found microscopic sites of injury (called microlesions) in the heart muscle. S. pneumoniae were found within these microlesions, indicating the bacteria were able to invade and multiply within the heart. Looking in more detail, the researchers identified dying heart muscle cellsin the tissue surrounding microlesions.

At the molecular level, the researchers found that the S. pneumoniae toxin pneumolysin was present within the microlesions and responsible for heart muscle cell death. They also showed that S. pneumoniae requires a molecule called CbpA to exit the bloodstream and invade the heart. Moreover, an experimental vaccine formulation composed of CbpA and a non-toxic version of pneumolysin generated antibodies that protected mice against cardiac invasion and heart damage.

Having obtained tissues from three rhesus macaques that had died from pneumococcal pneumonia, the researchers found cardiac microlesions that were similar in size and appearance to those seen in mice, but without the presence of S. pneumoniae bacteria. The situation was similar in cardiac samples from human patients who had died from invasive pneumococcal disease. Two of the samples (they looked at a total of nine) showed microlesions, but the lesions did not contain bacteria.

As the macaques and the human patients had been treated with antibiotics, the researchers wondered whether the bacteria had caused the lesions but subsequently been killed by the treatment. To test this, they infected mice with S. pneumoniae and treated them with a high-dose antibiotic (ampicillin) when the lesions were first apparent. The hearts of these mice looked similar to the macaques and human samples, with clear presence of microlesions but devoid of bacteria. As the researchers discuss, ampicillin acts by breaking bacteria apart and releasing their contents, including pneumolysin, and this could exacerbate the death of heart muscle cells. Alternative antibiotics that do not spill their bacterial targets' contents exist and might be advantageous.

Having shown for the first time that S. pneumoniae can directly damage the heart—which could help explain the link between pneumonia and adverse heart events—the researchers conclude that "research is merited to determine the true frequency of cardiac microlesions in patients hospitalized with invasive pneumococcal disease, if modifications in antibiotic therapy improve long-term outcomes, and if prevention of cardiac damage is an indication for vaccination."

More information: Streptococcus pneumoniae Translocates into the Myocardium and Forms Unique Microlesions That Disrupt Cardiac Function. PLoS Pathogens, 2014; 10 (9): e1004383 DOI: 10.1371/journal.ppat.1004383

Provided by Public Library of Science

Researchers debunk myth about Parkinson's disease

Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease. 

Using advanced computer models, neuroscience researchers at the University of Copenhagen have gained new knowledge about the complex processes that cause Parkinson's disease. The findings have recently been published in the prestigious Journal of Neuroscience.

The defining symptoms of Parkinson's disease are slow movements, muscular stiffness and shaking. There is currently no cure for the condition, so it is essential to conduct innovative research with the potential to shed some light on this terrible disruption to the central nervous system. Using advanced computer models, neuroscience researchers at the University of Copenhagen have gained new knowledge about the complex processes that cause Parkinson?s disease.

Dopamine is an important neurotransmitter which affects physical and psychological functions such as motor control, learning and memory. Levels of this substance are regulated by special dopamine cells. When the level of dopamine drops, nerve cells that constitute part of the brain's 'stop signal' are activated.

"This stop signal is rather like the safety lever on a motorised lawn mower: if you take your hand off the lever, the mower's motor stops. Similarly, dopamine must always be present in the system to block the stop signal. Parkinson's disease arises because for some reason the dopamine cells in the brain are lost, and it is known that the stop signal is being over-activated somehow or other. Many researchers have therefore considered it obvious that long-term lack of dopamine must be the cause of the distinctive symptoms that accompanies the disease. However, we can now use advanced computer simulations to challenge the existing paradigm and put forward a different theory about what actually takes place in the brain when the dopamine cells gradually die," explains Jakob Kisbye Dreyer, Postdoc at the Department of Neuroscience and Pharmacology, University of Copenhagen.

A thorn in the side

Scanning the brain of a patient suffering from Parkinson's disease reveals that in spite of dopamine cell death, there are no signs of a lack of dopamine – even at a comparatively late stage in the process.

"The inability to establish a lack of dopamine until advanced cases of Parkinson's disease has been a thorn in the side of researchers for many years. On the one hand, the symptoms indicate that the stop signal is over-activated, and patients are treated accordingly with a fair degree of success. On the other hand, data prove that they are not lacking dopamine," says Postdoc Jakob Kisbye Dreyer.

Computer models predict the progress of the disease

"Our calculations indicate that cell death only affects the level of dopamine very late in the process, but that symptoms can arise long before the level of the neurotransmitter starts to decline. The reason for this is that the fluctuations that normally make up a signal become weaker. In the computer model, the brain compensates for the shortage of signals by creating additional dopamine receptors. This has a positive effect initially, but as cell death progresses further, the correct signal may almost disappear. At this stage, the compensation becomes so overwhelming that even small variations in the level of dopamine trigger the stop signal – which can therefore cause the patient to develop the disease."

The new research findings may pave the way for earlier diagnosis of Parkinson's disease.

More information: Read the article in Journal of Neuroscience.

Provided by University of Copenhagen

World Alzheimer Report 2014 reveals persuasive evidence for dementia risk reduction

The World Alzheimer Report 2014 'Dementia and Risk Reduction: An analysis of protective and modifiable factors', released today, calls for dementia to be integrated into both global and national public health programmes alongside other major non communicable diseases (NCDs).

17 sept 2014--Alzheimer's Disease International (ADI) commissioned a team of researchers, led by Professor Martin Prince from King's College London, to produce the report. ADI is publishing this report, in conjunction with World Alzheimer's Day (21 September) and as a part of World Alzheimer's Month, an international campaign to raise awareness and challenge stigma.

The report reveals that control of diabetes and high blood pressure as well as measures to encourage smoking cessation and to reduce cardiovascular risk, have the potential to reduce the risk of dementia even in late-life. The report found that diabetes can increase the risk of dementia by 50%. Obesity and lack of physical activity are important risk factors for diabetes and hypertension, and should, therefore, also be targeted.

While cardiovascular health is improving in many high income countries, many low and middle income countries show a recent pattern of increasing exposure to cardiovascular risk factors, with rising rates of diabetes, heart disease and stroke.

Smoking cessation is strongly linked in the report with a reduction in dementia risk. For example, studies of dementia incidence among people aged 65 years and over show that ex-smokers have a similar risk to those who have never smoked, while those who continue to smoke are at much higher risk.

Furthermore, the study revealed that those who have had better educational opportunities have a lower risk of dementia in late-life. Evidence suggests that education has no impact on the brain changes that lead to dementia, but reduces their impact on intellectual functioning.

The evidence in the report suggest that if we enter old age with better developed, healthier brains we are likely to live longer, happier and more independent lives, with a much reduced chance of developing dementia. Brain health promotion is important across the life span, but particularly in mid-life, as changes in the brain can begin decades before symptoms appear.

The study also urges NCD programs to be more inclusive of older people, with the message that it's never too late to make a change, as the future course of the global dementia epidemic is likely to depend crucially upon the success or failure of efforts to improve global public health, across the population. Combining efforts to tackle the increasing global burden of NCDs will be strategically important, efficient and cost effective. Leading a healthier lifestyle is a positive step towards preventing a range of long-term diseases, including cancer, heart disease, stroke and diabetes.

However, survey data released by Bupa* has shown that many people are unclear about the causes and actions they can take to potentially reduce their risk of dementia. Just over a sixth (17%) of people realised that social interaction with friends and family could impact on the risk. Only a quarter (25%) identified being overweight as a possible factor, and only one in five (23%) said physical activity could affect the risk of developing dementia and losing their memories. The survey also revealed that over two thirds (68%) of people surveyed around the world are concerned about getting dementia in later life.

Professor Martin Prince, from King's College London's Institute of Psychiatry, Psychology & Neuroscience and author of the report, commented: "There is already evidence from several studies that the incidence of dementia may be falling in high income countries, linked to improvements in education and cardiovascular health. We need to do all we can to accentuate these trends. With a global cost of over US$ 600 billion, the stakes could hardly be higher."

Marc Wortmann, Executive Director, Alzheimer's Disease International said: "From a public health perspective, it is important to note that most of the risk factors for dementia overlap with those for the other major non communicable diseases(NCDs). In high income countries, there is an increased focus on healthier lifestyles, but this is not always the case with lower and middle income countries. By 2050, we estimate that 71% of people living with dementia will live in these regions, so implementing effective public health campaigns may help to reduce the global risk."

Professor Graham Stokes, Global Director of Dementia Care, Bupa, said: "While age and genetics are part of the disease's risk factors, not smoking, eating more healthily, getting some exercise, and having a good education, coupled with challenging your brain to ensure it is kept active, can all play a part in minimising your chances of developing dementia. People who already have dementia, or signs of it, can also do these things, which may help to slow the progression of the disease."

More information: The full report will be available at www.alz.co.uk/worldreport2014

The full survey results will be available at www.bupa.com/dementia

Provided by King's College London

The public's perception of the obesity epidemic

16 sept 2014--Obesity has been called a major health crisis and a national epidemic. Health authorities, including prominent spokespeople like Michelle Obama and the Surgeon General, have sounded the alarm, and the media have responded with a bombardment of stories about the state of the nation's waistline.

But does the American public understand the significance of the country's weight issue? Or have people become so accustomed to the "new normal" of excess weight that they don't recognize the problem? Data from the Roper Center for Public Opinion Archives tell the story.

Americans know there's an obesity problem

Since the earliest available CDC data in 1960, the obesity rate among American adults has increased nearly threefold. The number of overweight and obese children has more than tripled since the seventies. These dramatic changes have not gone unnoticed by the public. In 2000, 74 percent of adults in a Time/CNN poll said they believed there were more overweight kids today than when they were young.

Americans also increasingly see this high incidence of obesity as a serious problem for the country. In 1990, near the height of the U.S. AIDS epidemic, Americans were asked by the Los Angeles Times to name the most urgent health problems facing the nation. Less than 1 percent of the public mentioned obesity, far below the number saying AIDS (49 percent), cancer (31 percent), and non-disease issues like health care costs. The percentage of respondents mentioning obesity stayed in the single digits until 2004.

But the massive public health campaigns that have been undertaken over the past decade have clearly made an impression. In 2013, the proportion of the public citing obesity as one of the most urgent health problems had risen to 39 percent, outranking even cancer.

Americans increasingly understand the health risks of being overweight

In September 1955, President Dwight D. Eisenhower had a heart attack, and the nation watched anxiously as he spent weeks recovering in the hospital. In the wake of this incident, Americans were asked by Gallup what they believed the chief causes of heart attack to be. Nearly half blamed strain, tension, and anxiety, while another quarter said overwork or exhaustion. Though the American Heart Association (AHA) already recognized the links between cardiac disease and excess weight, only 5 percent of the public mentioned being overweight as a cause.

When a similar question about heart "trouble" was asked by the National Heart, Lung, and Blood Institute and Louis Harris and Associates in 1979, being overweight was mentioned by 34 percent of respondents, nearly as many as cited emotional pressure or anxiety. In 1998, the American Heart Association reclassified obesity as a "major and modifiable" risk factor in coronary heart disease. By 2009, recognition of the link between weight and heart disease was widespread: a Parade/Research!America poll found that an overwhelming 92 percent of the public recognized being overweight as a major risk factor for heart disease.

Public recognition of other health risks associated with being overweight has come more slowly. A 1965 Harris survey asked respondents what they thought the dangers were for them personally if they didn't "diet when they should." About 40 percent said heart attack, 10 percent high blood pressure. Only 4 percent said diabetes. When Harris asked the same question again in 1980, the number saying heart disease stayed about the same. Those mentioning high blood pressure and diabetes both increased, to 22 percent and 10 percent respectively.

In 2002, researchers on the major Diabetes Prevention Program study reported that pre-diabetic participants could slow or stop the onset of the disease with weight loss and management. A decade after this announcement, the message about diabetes had gotten across to most of the public. When asked by AP/NORC in 2012 to tell in their own words what the most serious health impacts were for being overweight or obese, 78 percent mentioned heart disease and 70 percent diabetes. However, only one in five (20 percent) mentioned high blood pressure, despite many decades of evidence of this relationship.

Americans see obesity as a problem for the country – but not themselves

While the CDC may classify more than one-third of Americans as obese and another third as overweight, the public don't see themselves that way. In a 2014 Gallup poll, just 5 percent say they are very overweight, while 35 percent say they are somewhat overweight, and 56 percent believe they are about right. These numbers are comparable to the results of a 1965 Harris poll, long before the rates of obesity began to climb rapidly, which found 38 percent of respondents considered themselves overweight, and 55 percent about right. In a 2013 Gallup poll, 51 percent said they would like to lose weight, a number essentially unchanged from the 52 percent who said so when the question was asked in 1990, despite an 11 percentage point increase in the obesity rate in that time frame.

My neighbors may be obese – but not my family and friends!

When asked about obesity in the area where they live, the public can see a reflection of the national epidemic. A 2008 Harvard/Robert Wood Johnson Foundation poll found over half (52 percent) of people thought obesity was a major problem in their community, while over a third (35 percent) said it was a minor problem. But when it came to their own families, just 17 percent of people reported being overweight as a major problem, in a 2009 Ipsos-McClatchy poll. A third said weight was a minor problem for their families, while nearly half (49 percent) said it was not a problem at all. A 2013 Gallup poll found just 8 percent of the public thought many of their family and close friends were overweight, 29 percent said some were, and 45 percent said only a few.

And certainly not my kids!

Only 12 percent of parents of children under 18 said in a 2012 AP/NORC poll that any of their children were overweight. Only one in five parents in a 2012 Harvard/RWJF/NPR poll said they were even somewhat concerned that their children might become overweight as adults. In comparison, one-third of children in the country are currently classified by health officials as overweight or obese, and a 2012 Duke University study projected that 42 percent of U.S. adults will be not just overweight, but obese, by 2040.

Polling data reveals how Americans' perceptions of their own weight are removed from their recognition of the overall public health problem. Perhaps because people judge themselves compared to what they see in others, the proportion of people seeing themselves as weighing more than they should stays stable, even as the number of overweight and obese people increases. Impressive progress has been made in making Americans aware of the increase in the obesity rate and the health risks of being overweight. However, until the gap is closed between Americans' perceptions of their weight and the hard facts about excess weight gain, obesity will continue to be a major problem for the country.

Provided by University of Connecticut