Study finds feeling in control may increase longevity

Credit: iStockphoto

06 feb 2014—Do you believe in your own ability to succeed, or do you believe life events are largely beyond your control?

Think carefully about your answer—it could affect your risk of mortality.

People who feel in control and believe they can achieve goals despite hardships are more likely to live longer and healthier lives, especially among those with less education, according to a new study by Brandeis University and the University of Rochester. The study was published online in the journal of Health Psychology.

Previous studies have shown that people with a high school diploma or less education tend to die younger than those with a college degree or graduate training. Yet, that's not a hard and fast rule. Why?

In this study, less educated people with higher perceived control in their life had a mortality rate three times lower than those with a lower sense of control. In fact, a high sense of control seemed to negate the mortality risks of lower education, says Margie Lachman, the Minnie and Harold Fierman Professor of Psychology, and an author on the paper.

"A high sense of control all but wipes out educational differences when it comes to mortality," Lachman says. "A person with less education but a high sense of control is practically indistinguishable from a person of high education."

Researchers determined attitudes about perceived control by asking participants to rank agreement to a set of statements. For example, participants were given the statement, "Sometimes I feel I am being pushed around in my life," and asked to rank their agreement from one (strongly disagree) to seven (strongly agree).

The study's public health implications are exciting, says Lachman.

"There are methods and strategies for improving one's sense of control, and educational experiences are one of them," Lachman says. "We could implement those approaches in educational and public health programs aimed at increasing health-promoting attitudes and behaviors and ultimately lowering mortality risks."

Provided by Brandeis University

Taking statins to lower cholesterol? New guidelines

Clinicians and patients should use shared decision-making to select individualized treatments based on the new guidelines to prevent cardiovascular disease, according to a commentary by three Mayo Clinic physicians published in this week's Journal of the American Medical Association.

05 feb 2014--Shared decision-making is a collaborative process that allows patients and their clinicians to make health care decisions together, taking into account the best scientific evidence available, as well as the patient's values and preferences.

In 2013, the American College of Cardiology and the American Heart Association issued new cholesterol guidelines, replacing previous guidelines that had been in place for more than a decade. The new guidelines recommend that caregivers prescribe statins to healthy patients if their 10-year cardiovascular risk is 7.5 percent or higher.

"The new cholesterol guidelines are a major improvement from the old ones, which lacked scientific rigor," says primary author Victor Montori, M.D., Mayo Clinic endocrinologist and lead researcher in the Knowledge and Evaluation Research Unit. "The new guidelines are based upon calculating a patient's 10-year cardiovascular risk and prescribing proven cholesterol-lowering drugs—statins—if that risk is high."

However, Dr. Montori cautions that the risk threshold established by the guideline panel is somewhat arbitrary. Instead he recommends that patients and their clinicians use a decision-making tool to discuss the risks and benefits of treatment with statins.

"Rather than routinely prescribing statins to the millions of adults who have at least a 7.5 percent risk of having a heart attack or stroke within 10 years, there is an opportunity for clinicians and patients to discuss the potential benefits, harm and burdens of statins in order to arrive at a choice that reflects the existing research and the values and context of each patient," he says.

"We're creating a much more sophisticated, patient-centered practice of medicine in which we move the decision-making from the scientist to the patient who is going to experience the consequences of these treatments and the burdens of these interventions," Dr. Montori explains. "Decision-making tools can democratize this approach and put it in the hands of millions of Americans who have their own goals front and center in the decision-making process."

Provided by Mayo Clinic

Hot weather deaths projected to rise 257 percent by 2050s, experts warn

The number of annual excess deaths caused by hot weather in England and Wales is projected to surge by 257% by the middle of the century, as a result of climate change and population growth, concludes research published online in the Journal of Epidemiology and Community Health.

04 feb 2014--The elderly (75+) will be most at risk, particularly in the South and the Midlands, the findings suggest.

The research team, from the London School of Hygiene and Tropical Medicine, and Public Health England, used time-series regression analysis to chart historic (1993-2006) fluctuations in weather patterns and death rates to characterise the associations between temperature and mortality, by region and by age group.

They then applied these to projected population increases and local climate to estimate the future number of deaths likely to be caused by temperature - hot and cold - for the 2020s, 2050s, and 2080s.

They based their calculations on the projected daily average temperatures for 2000-09, 2020-29, 2050-59 and 2080-89, derived from the British Atmospheric Data Centre (BADC), and population growth estimates from the Office of National Statistics.

The calculations indicated a significantly increased risk of deaths associated with temperature across all regions of the UK, with the elderly most at risk.

The number of hot weather days is projected to rise steeply, tripling in frequency by the mid 2080s, while the number of cold days is expected to fall, but at a less dramatic pace.

At the national level, the death rate increases by just over 2% for every 1ᵒC rise in temperature above the heat threshold, with a corresponding 2% increase in the death rate for every 1ᵒC fall in temperature below the cold threshold.

In the absence of any adaptive measures, excess deaths related to heat would be expected to rise by 257% by the 2050s, from an annual baseline of 2000, while those related to the cold would be expected to fall by 2% as a result of milder winters, from a current toll of around 41,000, but will still remain significant.

Those aged 85 and over will be most at risk, partly as a result of population growth - projected to reach 89 million by the mid 2080s - and the increasing proportion of elderly in the population, say the authors.

Regional variations are likely to persist: London and the Midlands are the regions most vulnerable to the impact of heat, while Wales, the North West, Eastern England and the South are most vulnerable to the impact of cold.

Rising fuel costs may make it harder to adapt to extremes of temperature, while increased reliance on active cooling systems could simply end up driving up energy consumption and worsening the impact of climate change, say the authors.

Better and more sustainable options might instead include shading, thermal insulation, choice of construction materials implemented at the design stage of urban developments, suggest the authors.

While the death toll from cold weather temperatures will remain higher than that caused by hot temperatures, the authors warn that health protection from hot weather will become increasingly necessary - and vital for the very old.

"As the contribution of population growth and ageing on future temperature related health burdens will be large, the health protection of the elderly will be important," warn the authors, recalling the social changes that have led to many elderly living on their own - a contributory factor to the high death toll in France in the 2003 heatwave.

More information: Climate change effects on human health: projections of temperature related mortality for the UK during the 2020s, 2050s, and 2080s, Online First, doi 10.1136-2013-202449

Provided by British Medical Journal

Parkinson gene: Nerve growth factor halts mitochondrial degeneration

The PINK1 gene plays a role in Parkinson’s disease. If the gene is switched off in the fly, the mitochondria (green) are damaged and the animal’s muscle fibres (red) disintegrate. The activation of the Ret receptor, which binds the growth factor GNDF in humans, counteracts this degeneration. Credit: MPI of Neurobiology / Klein

03 feb 2014—Neurodegenerative diseases like Parkinson's disease involve the death of thousands of neurons in the brain. Nerve growth factors produced by the body, such as GDNF, promote the survival of the neurons; however, clinical tests with GDNF have not yielded in any clear improvements. Scientists from the Max Planck Institute of Neurobiology in Martinsried and their colleagues have now succeeded in demonstrating that GDNF and its receptor Ret also promote the survival of mitochondria, the power plants of the cell. By activating the Ret receptor, the scientists were able to prevent in flies and human cell cultures the degeneration of mitochondria, which is caused by a gene defect related to Parkinson's disease. This important new link could lead to the development of more refined GDNF therapies in the future.

In his "Essay on the Shaking Palsy" of 1817, James Parkinson provided the first description of a disease that today affects almost 280,000 people in Germany. The most conspicuous symptom of Parkinson's disease is a slow tremor, which is usually accompanied by an increasing lack of mobility and movement in the entire body. These symptoms are visible manifestations of a dramatic change that takes place in the brain: the death of large numbers of neurons in the Substantia nigra of the midbrain.

Despite almost 200 years of research into Parkinson's, its causes have not yet been fully explained. It appears to be certain that, in addition to environmental factors, genetic mutations also play a role in the emergence of the disease. A series of genes is now associated with Parkinson's disease. One of these is PINK1, whose mutation causes mitochondrial dysfunction. Mitochondria are a cell's power plants and without them, a cell cannot function properly or regenerate. Scientists from the Max Planck Institute of Neurobiology and their colleagues from Munich and Martinsried have now discovered a hitherto unknown link that counteracts mitochondrial dysfunction in the case of a PINK1 mutation.

The PINK1 gene emerged at a very early stage in evolutionary history and exists in a similar form for example in humans, mice and flies. In the fruit fly Drosophila, a mitochondrial defect triggered by a PINK1 mutation manifests in the fraying of the muscles. Less visible, the flies' neurons also die. The scientists studied the molecular processes involved in these changes and discovered that the activation of the Ret receptor counteracts the muscle degeneration. "This is a really interesting finding which links the mitochondrial degeneration in Parkinson's disease with nerve growth factors," reports Rüdiger Klein, the head of the research study. Ret is not an unknown factor for the Martinsried-based neurobiologists: "We already succeeded in demonstrating a few years ago in mice that neurons without the Ret receptor die prematurely and in greater numbers with increasing age," says Klein.

The Ret receptor is the cells' docking site for the growth factor GDNF, which is produced by the body. Various studies carried out in previous years showed that the binding of GDNF to its Ret receptor can prevent the early death of neurons in the Substantia nigra. However, clinical studies on the influence of GDNF on the progression of Parkinson's in patients did not lead to any clear improvement in their condition.

The new findings from basic research suggest that the mitochondrial metabolism is boosted or re-established through Ret/GNDF. "Based on this finding, existing therapies could be refined or tailored to specific patient groups," hopes Pontus Klein, who conducted the study within the framework of his doctoral thesis. This hope does not appear to be completely unfounded: The scientists have already discovered a Ret/GDNF effect in human cells with a PINK1 defect similar to that observed in the fruit fly. It may therefore be possible to search for metabolic defects in the mitochondria of Parkinson's patients in future. A specially tailored GDNF therapy could then provide a new therapeutic approach for patients who test positively.

More information: Pontus Klein, A. Kathrin Müller-Rischart, Elisa Motori, Cornelia Schönbauer, Frank Schnorrer, Konstanze F. Winklhofer, Rüdiger Klein, Ret rescues mitochondrial morphology and muscle degeneration of Drosophila Pink1 mutants. The EMBO Journal. 29 January, 2014

Provided by Max Planck Society

Psychological well-being is important for physical health

In a comprehensive review  published in the current issue of Psychotherapy and Psychosomatics Carol Ryff described how major research findings have supported the link between psychological well-being and physical health.

02 feb 2014--The model of psychological well-being was developed more than two decades ago to address neglected aspects of positive functioning such as purposeful engagement in life, realization of personal talents and capacities, and enlightened self-knowledge.

The conceptual origins of this formulation are revisited and scientific products emerging from 6 thematic areas are examined: (1) how well-being changes across adult development and later life; (2) what are the personality correlates of well-being; (3) how well-being is linked with experiences in family life; (4) how well-being relates to work and other community activities; (5) what are the connections between well-being and health, including biological risk factors, and (6) via clinical and intervention studies, how psychological well-being can be promoted for ever-greater segments of society.

Together, these topics illustrate flourishing interest across diverse scientific disciplines in understanding adults as striving, meaning-making, proactive organisms who are actively negotiating the challenges of life. A take-home message is that increasing evidence supports the health protective features of psychological well-being in reducing risk for disease and promoting length of life. A recurrent and increasingly important theme is resilience - the capacity to maintain or regain well-being in the face of adversity.

More information: Ryff C.D. Psychological Well-Being Revisited: Advances in the Science and Practice of Eudaimonia. Psychother Psychosom 2014;83:10-28. DOI: 10.1159/000353263

Provided by Psychotherapy and Psychosomatics

Researchers discover an epigenetic lesion in the hippocampus of Alzheimer's

In pink is the location and structure of the brain hippocampus, the region where the epigenetic lesion was found in Alzheimer's patients. Credit: IDIBELL

01 feb 2014--Alzheimer's disease can reach epidemic range in the coming decades, by the increasing average age of society. There are two key issues for Alzheimer's disease: there is currently no effective treatment and it has been described very few associated genetic changes (mutations) which reduces the number of targets for future therapies.

Alzheimer's disease

Pathologically, Alzheimer 's disease is characterized by the accumulation of protein deposits in the brain of patients. These deposits are formed by plates of a protein called amyloid-beta and rolled tangles of tau protein . The root cause of these lesions in most cases is unknown, but specific alterations in regulating genes expression might be involved.

Today , the prestigious international journal in neurology Hippocampus publishes an article led by Manel Esteller, Director of Epigenetics and Cancer Biology , Institute of Biomedical Research of Bellvitge (IDIBEL ) , ICREA researcher and Professor of Genetics at the University of Barcelona,with the collaboration of the Institute of Neuropathology IDIBELL led by Isidre Ferrer, demonstrating for the first time the existence of an epigenetic lesion in the hippocampus of the brain of patients with Alzheimer.

Switches in the hippocampus

" We first started studying 30,000 molecular switches that turn on and off genes in the hippocampal region in the brains of Alzheimer patients in different stages of disease and compared with that of healthy patients of the same age. We note that dusp22 gene switch off (methylated) as the disease advances" explained Manel Esteller, director of the study.

"But more importantly" continues "was the discovery that this gene regulates tau protein. Perhaps therefore the accumulation of tau protein produced in the brain of patients with Alzheimer results from dusp22 epigenetic inactivation " .

According Esteller " the finding is relevant not only to determine the causes of the disease, but also to test potential treatments in the future to act on these epigenetic molecular switches " .

More information: Sanchez-Mut JV, Aso E, Heyn H, Matsuda T, Bock C, Ferrer I, Esteller M. Promoter hypermethylation of the phosphatase DUSP22 mediates PKA-dependent TAU phosphorylation and CREB activation in Alzheimer's disease.Hippocampus, DOI: 10.1002/hipo.22245, 2014.

Provided by IDIBELL-Bellvitge Biomedical Research Institute

Some secrets of longevity: Trim the weight, expand your education, and enjoy your job

Mortality rates have increased among less-educated American women, and even wealthy Americans have a shorter life expectancy than their European counterparts, said Harvard Professor Lisa Berkman (far right) during the HSPH forum event “Living Longer and Happier Lives: The Science Behind Healthy Aging.” Joining Berkman were Thomas Perls (from far left), William Mair, and Francine Grodstein. Credit: Emily Cuccarese/HSPH

31 jan 2014--The average life expectancy in the United States has fallen behind that of other industrialized nations as the American income gap has widened. In addition, better health habits, including those involving weight control, nutrition, and exercise, clearly influence the effects of aging among segments of the U.S. population.

"Widening inequalities in the U.S. are growing over time, not decreasing," said Lisa Berkman, the Thomas D. Cabot Professor of Public Policy and of Epidemiology at the Harvard School of Public Health (HSPH) and director of the Harvard Center for Population and Development Studies.

Addressing an HSPH forum Tuesday called "Living Longer and Happier Lives: The Science Behind Healthy Aging," she said mortality rates have increased among less-educated American women, and even wealthy Americans have a shorter life expectancy than their European counterparts.

"Diet does seem to make a difference," said Francine Grodstein, professor of epidemiology at HSPH and professor of medicine at Harvard Medical School. The Nurses' Health Study, a large longitudinal study that dates back to the 1970s, is a foundation for many of these conclusions.

"The higher our body weight and body mass index, the less likely we are to live older, happier, healthier lives," she said.

William Mair, HSPH assistant professor of genetics and complex diseases, said a study that has gained a lot of attention found that reducing body weight by 20 percent in mice increased their longevity.

"If you take almost any organism, a fruit fly or a mouse, and reduce food intake by 20 percent, you get pronounced longer life," he said. The frontier lies in understanding this process on a molecular level to apply the findings to human nutrition, he said.

Medical treatment of older people also needs to change because the elderly contract multiple diseases, so curing one at a time does not extend life, he said. "We need to work on the commonality of diseases," and find what is fundamental "to squeeze the disease period to later in life."

A great deal of scientific attention and interest is focused on mental health and memory as people age. The better educated are less likely to develop dementia, said Grodstein, though studies don't explain why. "Nobody thinks that sitting in a classroom prevents dementia," she said. So scientists are trying to hone in on what mental processes make a difference.

Berkman noted that continuing to work at creative jobs with autonomy and control over schedules and conditions are proven pluses for better health. Even remaining in blue-collar jobs is better than being inactive. In fact, societies with earlier retirement have steeper and stronger declines in health and enjoyment of life.

"When people designed work, they did not design it for there to be 30 years afterwards, like a vacation," she said. Many structures and policies have been in place since the 1950s, when many people died a year or two after they started collecting Social Security.

A promising area in warding off dementia involves taking up a personal challenge such as learning to play an instrument or to speak another language, said Thomas Perls, a Boston University professor of medicine and director of the New England Centenarian Study.

There is evidence that such mentally challenging pursuits build "functional reserves" that delay dementia, he said. Still, it hasn't been proven that those who master multiple instruments necessarily live longer or how the process relates to memory loss.

"Becoming really good at a difficult crossword puzzle," he wondered, "does that help you find your keys?"

Perls said there are more centenarians than ever to study. Some have terrible health habits, but their genes counterbalance them.

"Twenty percent of the population has the genetic wherewithal to get to be 100," he said. "The next question: Would you want to live to 100?"

Provided by Harvard University

Testosterone therapy might increase heart attack risk

Researchers say risk doubles after treatment starts for men under 65 with heart problems and all men over 65.

30 jan 2014—Testosterone therapy—widely advertised as a way to help men improve a low sex drive and reclaim diminished energy—might raise the risk of heart attack, according to new research.

The increased risk was found in men younger than 65 with a history of heart disease, and in older men even if they didn't have a history of the disease. In both groups, heart attack risk doubled in the 90 days after the men began testosterone therapy, said researcher William Finkle, CEO of Consolidated Research, in Los Angeles.

"It was more or less the same increase in risk," Finkle said.

Testosterone therapy typically is given in gel, patch or injection form, and is widely promoted in television advertisements about "low T." Although the treatment risk to men over 65 has been documented in previous research, Finkle said, the new study is believed to be the first to look at men under 65.

The study, published online Jan. 29 in the journal PLoS One, was conducted by a research team that included experts from Consolidated Research, the U.S. National Cancer Institute and the University of California, Los Angeles.

It was triggered by a 2010 report in the New England Journal of Medicine, Finkle said. In that study, a clinical trial of testosterone gel in men over 65 was halted early after an increase in heart attacks and other heart problems occurred in the group using the testosterone supplements.

Finkle's team used data from Truven Health Analytics, which gathers nationwide information on patient care. The researchers looked at the medical records of nearly 56,000 men who had been prescribed testosterone therapy—more than 48,000 of whom were under age 65.

"We identified the [timing of the] first prescription and followed them for 90 days," Finkle said. The risk for heart attack doubled in that 90-day period for men over 65 and those under 65 with a history of heart disease, the researchers found.

When they continued to follow the men for another 90 days, the researchers said, the risk declined to the level it was at the study's start for men who did not refill their initial prescription.

Even though the two-fold increase in risk in younger men was seen only in those with a history of heart disease, Finkle said he's uncertain of the therapy's safety in younger, healthy men.

"We don't have enough evidence to say testosterone supplements in men under age 65 without heart disease are safe," he said.

Although the researchers found an association between testosterone therapy and increased risk of heart attack, the study did not prove a cause-and-effect relationship.

The study authors also did not examine the explanation for the link, but Finkle said it could be tied to the effect of testosterone in blood.

"The theory is that testosterone most likely promotes clotting," he said. In older men who tend to have thinner vessels, that clotting could cause problems, he said.

The supplements might also increase men's circulating estrogen, the researchers said. Estrogen therapy has been linked to an increase in heart troubles in both men and women.

AbbVie and Actavis, the makers of testosterone therapies, did not respond to requests for comment on the study.

But one expert not involved in the research expressed skepticism, citing flaws in the study design.

"Based on the best available data, testosterone replacement still appears to be safe ... for properly selected patients," said Dr. Ryan Terlecki, director of the Men's Health Clinic at the Wake Forest Baptist Medical Center.

Among the flaws in the study, Terlecki said, was the use of information obtained from medical claims data, which makes it uncertain which men actually used the testosterone.

"This is important since compliance can be poor, especially with topical formulations," he said. Terlecki reported that he previously worked as a consultant for Auxilium, which makes testosterone therapy.

The researchers did not have information on why the testosterone therapy was prescribed, so it could have been prescribed inappropriately, Terlecki said. He also cited other data that has linked low testosterone—not testosterone therapy—to an increased risk of heart disease.

Men who are discussing testosterone therapy with their doctors "should add the risk of heart attack to the discussion of the risks and benefits of testosterone," Finkle said.

Terlecki said men who have a lack of energy should first see their doctor and ask about screening for depression and other conditions—such as thyroid disease or B12 deficiency—that could also be the cause.

Testosterone therapy is marketed so successfully that the independent medicine website Drugs.com reported that sales of Androgel exceeded sales of Viagra in 2013, according to UCLA researchers.

More information: To learn more about low testosterone, visit the Urology Care Foundation.

High-intensity strength training shows benefit for Parkinson's patients

29 jan 2014—Researchers at the University of Alabama at Birmingham say that high-intensity strength training produced significant improvements in quality of life, mood and motor function in older patients with Parkinson's disease. The findings were published Jan. 9 online in the Journal of Applied Physiology.

Fifteen subjects with moderate Parkinson's underwent 16 weeks of high-intensity resistance training combined with interval training designed to simultaneously challenge strength, power, endurance, balance and mobility function. Before and after the 16 weeks, the subjects were compared to age-matched controls who did not have Parkinson's and did not undergo the exercise regimen.

"We saw improvements in strength, muscle size and power, which we expected after rigorous weight training; but we also saw improvement in balance and muscle control," said Marcas Bamman, Ph.D., professor in the Department of Cell, Developmental and Integrative Biology and lead author of the study. "We also saw improvement in cognition, mood and sense of well-being."

Parkinson's disease is a debilitating, neurodegenerative disease that dramatically affects mobility function and quality of life. Patients often experience weakness, low muscle power and fatigue.

Bamman, who heads the UAB Center for Exercise Medicine, devised a strenuous exercise regimen for the participants. Subjects performed three sets of eight to 12 repetitions of a variety of strength training exercises, such as leg or overhead presses, with a one-minute interval between sets for high-repetition, bodyweight exercises, such as lunges or pushups.

"We pushed these patients throughout the exercise period," said Neil Kelly, M.A., a graduate student trainee and first author of the study. "We used a heart rate monitor to measure exercise intensity—keeping the heart rate high through the entire 40-minute session."

Bamman says this was the first study of its kind to look at the biology of the muscles. Biopsies of muscle tissue were collected before and after the 16 weeks.

"We found favorable changes in skeletal muscle at the cellular and subcellular levels that are associated with improvements in motor function and physical capacity," Bamman said.

Physicians who treat Parkinson's patients, such as UAB's David Standaert, M.D., Ph.D., chair of the Department of Neurology, say they have long believed that exercise is beneficial to their patients.

"What we do not know is what kind of exercise and how much exercise will prove best for individual patients with Parkinson's," Standaert said. "This study is concrete evidence that patients can benefit from anexercise program and can do so rapidly in only 16 weeks."

Standaert says he hopes this study will open the door to a more complete understanding of the role of exercise in this patient population.

"My patients who participated in the study told me that they enjoyed the exercise regimen and that they saw distinct improvement in their health and physical condition," he said. "Future studies should be able to help answer questions such as optimal frequency, intensity and type of exercise."

Study participants showed significant improvement of six points on average on a measure called the Unified Parkinson's Disease Rating Scale. On another measure, a seven-point fatigue scale, the group improved from a score above the clinical threshold for undue fatigue to a score below this threshold.

A sit-to-stand test showed that, after strength training, participants dropped from requiring 90 percent of maximum muscle recruitment to rise to a standing position to just 60 percent, which put them on par with their same-age, non-Parkinson's peers.

"These are all indications that strength training produced a major improvement in the ability to activate muscles, to generate power and to produce energy," Bamman said, "all of which can contribute to improved quality of life and reduction of injury risk from falls."

The study was funded by the UAB School of Medicine and the Department of Neurology, along with the UAB Center for Exercise Medicine. Bamman hopes the findings will pave the way for larger studies to define optimal exercise doses for Parkinson's patients across the disease spectrum.

"This is the first step in an important direction to maximize the therapeutic benefits of exercise training for people with Parkinson's disease," he said.

Provided by University of Alabama at Birmingham

Telomere length prognostic for 50 to 75 year-old men with ACS

28 jan 2014—For men aged 50 to 75 years with acute coronary syndrome, short telomeres are independently associated with worse prognosis, according to a study published in the Feb. 1 issue of The American Journal of Cardiology.

Jose-Angel Perez-Rivera, M.D., from the University Hospital of Salamanca in Spain, and colleagues assessed the prognostic value of telomere length, measured by quantitative polymerase chain reaction in peripheral blood leukocytes of 203 men admitted with acute coronary syndrome. The men were classified into two groups according to age: 50 to 75 years, and older than 75 years. Patients underwent more than 600 days of clinical follow-up and a prognostic combined event was defined.

The researchers found that for men aged 50 to 75 years, those with short telomeres had significantly worse prognosis (P < 0.05), but this association was not seen for men aged older than 75 years (P = 0.91). For men aged 50 to 75 years, Cox analysis confirmed short telomeres as an independent prognostic risk factor.

"In conclusion, telomere length is a good predictor of cardiovascular prognosis in men admitted for acute coronary syndrome, but this relation depends on the chronological age of the population studied," the authors write.

More information: Abstract 

Process that turns 'good cholesterol' bad discovered

Cleveland Clinic researchers have discovered the process by which high-density lipoprotein (HDL) – the so-called "good cholesterol" – becomes dysfunctional, loses its cardio-protective properties, and instead promotes inflammation and atherosclerosis, or the clogging and hardening of the arteries. Their research was published online today in the journalNature Medicine.

27 jan 2014--The beneficial and cardio-protective properties of HDL have been studied and reported extensively, yet all clinical trials of pharmaceuticals designed to raise HDL levels have so far failed to show that they significantly improve cardiovascular health. This disconnect, as well as recent research showing that a protein abundant in HDL is present in an oxidized form in diseased artery walls, spurred the research team – led by Stanley Hazen, M.D., Ph.D., Vice Chair of Translational Research for the Lerner Research Institute and section head of Preventive Cardiology & Rehabilitation in the Miller Family Heart and Vascular Institute at Cleveland Clinic – to study the process by which HDL becomes dysfunctional.

Apolipoprotein A1 (apoA1) is the primary protein present in HDL, providing the structure of the molecule that allows it to transfer cholesterol out of the artery wall and deliver it to the liver, from which cholesterol is excreted. It's apoA1 that normally gives HDL its cardio-protective qualities, but Dr. Hazen and his colleagues have discovered that in the artery wall during atherosclerosis, a large proportion of apoA1 becomes oxidized and no longer contributes to cardiovascular health, but rather, contributes to the development of coronary artery disease.

Over the course of more than five years, Dr. Hazen and his colleagues developed a method for identifying dysfunctional apoA1/HDL and discovered the process by which it is oxidized and turned dysfunctional in the artery wall. They then tested the blood of 627 Cleveland Clinic cardiology patients for the dysfunctional HDL and found that higher levels raised the patient's risk for cardiovascular disease.

"Identifying the structure of dysfunctional apoA1 and the process by which it becomes disease-promoting instead of disease-preventing is the first step in creating new tests and treatments for cardiovascular disease," said Dr. Hazen. "Now that we know what this dysfunctional protein looks like, we are developing a clinical test to measure its levels in the bloodstream, which will be a valuable tool for both assessingcardiovascular disease risk in patients and for guiding development of HDL-targeted therapies to prevent disease."

The research also points toward new therapeutic targets for pharmaceuticals, such as those designed to prevent the formation of dysfunctional HDL and the development or progression of atherosclerosis.

More information: An abundant dysfunctional apolipoprotein A1 in human atheroma, DOI: 10.1038/nm.3459

Provided by Cleveland Clinic

Researchers grapple with probabilities of species mortality

Max Planck scientists have compiled a catalogue of 46 species and their respective mortality and birth rates. Credit: Owen Jones (MaxO), Alexander Scheuerlein (MPIDR) et. al/ Nature 2013

26 jan 2014--Despite aging being one of the hottest topics in the media recently, scientists have no coherent explanation for it. New demographic data on humans, animals and plants for the first time unveils an extraordinary diversity of aging processes that no existing evolutionary theory can account for. Both life spans and mortalities vary from species to species. The fact that the probability of dying rises with age applies to humans, but is not principally true. This is shown by a catalogue of 46 species with their respective mortality and fertility rates, which has now been published in the science journal Nature. It is the result of a long-term data collection project led by scientists at the Max Planck Institute for Demographic Research (MPIDR) in Rostock, Germany, and at the Max-Planck Odense Center on the Biodemography of Aging (MaxO) in Odense, Denmark.

Not only are previous explanations unable to deal with life spans ranging from a few days (fruit fly), to decades (humans), to centuries (hydra), but they are also unable to account for variations in the death rate. Common theories assert that the probability of dying rises with age, as for humans. However, the researchers cataloged species such as the white mangrove and the desert tortoise whose probability of dying actually decreases with age. In addition, fertility periods of some species also challenge common theories.

Previous attempts to explain aging claim that creatures only invest in self-preservation until they have reproduced successfully and raised their offspring. Following this line of reasoning, when the end of the fertility period approaches, the body should start to decay – which is known as senescence, or aging.

For humans this is only partly true. According to the Nature study, mortality of modern Japanese women rises constantly after childhood. But contradictorily, humans still live for a long time after fertility has ceased. Today, many people stay healthy until they are grandparents and their probability of dying is correspondingly small. Only at advanced ages is mortality growing rapidly. For example, in Japanese women 100 years old, mortality reaches more than 20 times their lifetime average.

This makes humans a real oddity. No other species in the researcher's catalog has a mortality curve which rises that sharply. Even among other mammals, death rates reach no more than five times the lifetime average. Why evolution developed such big differences is a mystery to Biologists.

For many species aging is turned upside down

Current theories are especially at odds with two groups of species for which the concept of aging appears to be turned upside down. On the one hand there are creatures whose mortality stays constant throughout their whole life, like hydra or the hermit crab. Their bodies do not seem to degenerate during their lifetime which can be understood as the absence of aging. And there are even species whose probability of dying decreases as they grow older, like the red gorgonian (a coral), the netleaf oak and the desert tortoise. Their risk of dying obviously never becomes zero, but when they are old they are more likely to survive until their next birthday than when they were in their youth.

There is another belief that the new data catalogue disproves: the idea that species with a short life span die so soon because they age so quickly. This would mean that their mortality rises strongly throughout life. However, sometimes the contrary is the case, such as in the tundra vole. Its mortality increases only moderately until it reaches two times its lifetime average at old age. Nevertheless, this vole rarely survives beyond one year. Humans, however, are living for an entire century more and more often, despite the fact that their risk of dying skyrockets at old age (up to more than 20 times the lifetime average).

Data will pave the way for a unified theory of aging

"Surprisingly, one can hardly imagine a type of life course that is not found in nature," says MaxO researcher Owen Jones. This applies not only for mortality but also for fertility. While women become infertile after a limited childbearing period in the first half of their lives, fertility rises until almost the end of the lifespan for the alpine swift. And the yellow baboon has offspring throughout its life without any influence of age. "One reason why we still lack a unified theory of aging is that our view on aging was always biased because we had data only for a very restricted selection of species," says biodemographer Alexander Scheuerlein from MPIDR. There have long been high quality demographic records for hundreds of mammals and birds but very few for other vertebrates or invertebrates. Extremely little is known about algae, fungi or bacteria. In order to understand why evolution created aging, much more comprehensive data on all species have to be collected, says Alexander Scheuerlein.

More information: Owen R. Jones, Alexander Scheuerlein, et al. Diversity of ageing across the tree of life, Nature 2013, DOI: 10.1038/nature12789 Published online 08 December 2013

Provided by Max Planck Society

For seniors with dementia, the choice to live alone can be a risky one

Study identifies safety issues, lack of social activities and health care.

25 jan 2014—For the millions of Americans with dementia, staying at home for as long as possible is a common goal. But independent living can pose certain risks for these adults—and prove challenging for family caregivers.

A new study of more than 250 Baltimore residents with dementia found unmet needs, especially concerning safety, health and meaningful activities, in almost all cases.

"Clearly, the biggest unmet need was in the area of personal and home safety," said lead researcher Betty Black, an associate professor in the department of geriatric psychiatry at the Johns Hopkins School of Medicine in Baltimore.

"Ninety percent of people in our sample needed to address safety issues at home," Black said. "That included things like fall risk management and wander risk management that really could be addressed perhaps by making alterations in one's home, like grab bars in bathrooms. Or restricting someone's access to tools that might be dangerous to them."

The study, published recently in the Journal of the American Geriatrics Society, also took a comprehensive look at the unmet needs of the caregivers. The vast majority lacked referrals to support services and had no education on how to function in their role.

The average age of dementia patients in the study was 83. More than 60 percent of study participants also had general health care and medical needs that went unaddressed.

"That really involved whether they had been to their primary care physician in the last year, for example, or whether they needed care from a medical sub-specialist, like a rheumatologist or cardiologist," Black said. "Or addressing issues like dental, vision and hearing problems."

Black said it's possible that managing safety and health problems early could reduce costly hospital readmissions, a big problem among people with mental impairment.

Many with Alzheimer's may not have been diagnosed with the disease

It's estimated that 5.4 million people in the United States have Alzheimer's disease or another type of dementia. About 70 percent live at home, according to background information in the study.

The authors found that nearly one-third of study participants had never received a dementia diagnosis or evaluation. Larger-scale national research suggests an even bigger gap.

"What we think now is that about half of the people with Alzheimer's disease have a diagnosis," said Beth Kallmyer, vice president of constituent services at the Alzheimer's Association. "That means that half don't even know they have Alzheimer's."

The Baltimore researchers looked into whether people had meaningful activities in their lives and weren't just sitting in front of a TV. About half did not, whether due to an unmet need for adult day care, senior services or in-home activities.

Meaningful activities are tailored to a person's interests and capabilities, and include "even doing simple activities around the house," Black said. "Like folding towels or helping to make a salad or setting the table—doing things that they may still know how to do, and can do, and feel that they're engaged in daily life, rather than simply sitting."

The researchers also found gaps in legal issues and advanced care planning for 48 percent of people with dementia. Several were still designated as having power of attorney for a spouse who was now their caregiver.

To their surprise, the researchers found that people with the mildest dementia and least difficulty functioning had more unmet needs than people with severe impairment.

Long-distance caregiving often not the best solution

They also discovered that people with dementia who have long-distance caregivers can fall through the cracks.

"One of the biggest challenges is when you're not living in close proximity—Mom lives in San Diego and the daughter lives in Seattle," said gerontologist Sara Shelton, owner of Seattle Aging Solutions. She said it's easy to be misled by cheerful "everything's fine" responses when you check in with your parents.

Black noted that "there's some effort to make use of technology" to stay in touch with mentally failing family members. "Like Skype and [other methods] that kind of allow people to have a sense of that person, even if they're not close by."

Dr. Alex Smith, at the division of geriatrics at the University of California, San Francisco, said the new study was needed.

"We know a heck of a lot about the people who are living in nursing homes because there is so much data available about them," Smith said. "It's so much harder to study the people who are living in the community with dementia—when that is the overwhelming majority of people."

In the Dec. 26 New England Journal of Medicine, Smith detailed the case of a 96-year-old widower in extremely bad health who insisted on living alone, and refused care from "strangers" at home. His son, living at a distance, was concerned about the unsafe, unsanitary conditions he found during monthly visits.

Smith suggested that it might be feasible for physicians to make at least an initial home visit to such patients. Such visits could give doctors a truer picture of the patient's living conditions and safety, and help set realistic thresholds for when it would be too hazardous for them to stay in the home.

Kallmyer noted that the new Baltimore study didn't delve into the cost of care. "It's really expensive," she said. "You know, if you can afford to pay a private duty companion to come in at $20 an hour and take care of your family 24/7, that's going to help you have choices there. And some people don't have that option."

The new study is part of ongoing research to determine whether the use of in-depth needs assessments, followed up by care coordination, would be effective on a larger scale. If evidence is strong, Black said, such interventions could perhaps be covered by publicly funded programs like Medicare.

When it comes to living in the community, the needs and capabilities of the caregiver also come into play, not just the needs of the person with dementia, Black said. "It involves safety and quality of life for both those individuals."

Part one of a two-part series. Tomorrow: What about the caregiver's needs?

High-protein diets, like the Dukan diet, increase the risk of developing kidney disease

A Wistar rat like those used in this experiment.

High-protein diets, like the popular Dr. Dukan diet, increase the long-term risk of developing kidney disease and have a negative effect on renal urinary and morphological markers. What's more, they may promote serious pathologies like nephrolithiasis (calcium kidney stones) because they drastically reduce urinary citrate (an inhibitor of calcium salt crystallization) and urinary pH, and increase urinary calcium (to compensate for the metabolic acidity caused by excess protein).

University of Granada scientists have proved this in an experiment in rats that examined the effects of a high-protein diet on renal urinary, plasma and morphological parameters.

The researchers studied 20 Wistar rats, divided into two groups of 10. The first group were fed a high-protein diet of commercial hydrolysed protein supplements with a 45% protein level. The control group were fed a normal protein diet. The experiment lasted 12 weeks, which is the equivalent of 9 years in human terms.

10 per cent weight loss

The results showed that the rats on a high-protein diet lost up to 10% of their body weight over the 12 weeks with no improvement in their plasma lipid profile. Moreover, urinary citrate in these rats was 88% lower and urinary pH was 15% more acidic. In the animals fed a high-protein diet, kidney weight increased by 22%, glomerular area—the network of capillaries that filter blood in the kidneys—by 13%, and the mesangium—a collagen structure surrounded by these capillaries—by 32%.

The results of this study lead the principle author, Dr Virginia A. Aparicio of the University of Granada Department of Physiology, to stress the need to closely monitor anyone on a high-protein diet. The Dukan diet, and others like it, can have serious long-term adverse effects on their health.

She warns that the negative effects of high-protein diets on the kidney also depend on the presence of other nutrients in the diet. "Eating large amounts of fruit and vegetables reduces the risk of kidney stones forming—probably due to their high potassium and magnesium content, which compensates for the acidity of the high-protein diet", Dr Aparicio concludes.

More information: High-protein diets and renal status in rats V. A. Aparicio, E. Nebot, R. García-del Moral, M. Machado-Vílchez, J. M. Porres, C. Sánchez and P. Aranda Nutrición Hospitalaria. 2013;28 (1):232-237 ISSN 0212-1611 CODEN NUHOEQ S.V.R. 318

Provided by University of Granada

Alzheimer's drugs fail, but lessons are learned

DAD (Disability Assessment for Dementia) scores worsened on average during the 78-week trial, with "bapi" (dotted blue line) showing no improvement over placebo. This data is from the trial with APOE allele carriers. Credit: Salloway et. al.

Dr. Stephen Salloway pulls no punches in describing the results of two clinical trials of the Alzheimer's drug bapineuzumab that he helped to lead. The antibody failed to produce cognitive improvement for volunteers compared to a placebo, he and colleagues report Jan. 23 in the New England Journal of Medicine.

23 jan 2014--"It is very disappointing, especially to the terrific and dedicated patients and their famililes," said Salloway, professor of neurology and psychiatry in the Warren Alpert Medical School of Brown University, director of neurology and the Memory and Aging Program at Butler Hospital, and lead author of the study. "So much effort went into this trial. Alzheimer's is a difficult and complex disease, and we are moving forward."

As much as the negative findings stung the patient, medical, and investor communities when they first became public in 2012, Salloway said that in the intervening time, researchers have come to understand several important lessons that they are moving aggressively to apply to a next round of research.

"We don't have the luxury of time," Salloway said. "There is an urgency that doesn't allow us to wait."

Antibody drugs like bapineuzumab—"bapi"—bind to and trigger clearance of amyloid beta proteins that form harmful plaques in the brains of Alzheimer's patients. (The antibody solanezumab, which was also tested in trials with similarly disappointing results published this week in NEJM, binds amyloid beta proteins in the blood, helping pull amyloid out of the brain.)

Important lessons of the bapi trials, Salloway said, are to test the drugs only with people who are building up the amyloid beta plaques the drugs address, to give drugs in doses that safely produce greater amyloid lowering, and to combine disease modifying treatments that might be complementary.

Drug combinations rather than single drugs, Salloway noted, have proven to be the answer not only for some forms of cancer, but also for converting other previously incurable problems, such as HIV, into manageable long-term conditions.

Another lesson may be to test these treatments at an earlier stage when amyloid plaques are mounting but before symptoms of cognitive decline have set in.

Salloway and a multicenter team of colleagues conducted two randomized, controlled, double-blinded trials, sponsored by bapi's manufacturers Janssen Alzheimer Immunotherapy and Pfizer. One trial tested the drug in 1,121 carriers of the APOE gene allele that is associated with a higher risk of Alzheimer's disease. The other evaluated it in 1,331 people without the allele. All participants were between 50 and 88 years old and had MRI scans and cognitive test scores indicating "probable" Alzheimer's disease.

Participants received the drug intraveneously every 13 weeks for 78 weeks. At each session they took cognitive tests. Subsets of participants also provided brain scans and fluid samples for various biomarkers, such as levels of amyloid beta plaques and tau protein associated with degeneration of brain cells. Early on researchers stopped administering the highest of three doses because of high levels of amyloid-related "fluid shifts" on MRI, most likely due to changes in amyloid in small arteries.

When researchers tallied the main measures of performance on cognitive tests, it became clear that bapi did nothing significant either for APOE carriers or noncarriers compared to placebo. In each group, cognitive decline continued unabated.

The researchers did find a benefit in two secondary measures: By week 71 they saw that bapi produced a significant reduction in phospho-tau concentration in the spinal fluid of APOE carriers, a indicator of neurodegeneration. In carriers who got the placebo, phospho-tau continued to rise. PET scans also showed less amyloid buildup in carriers who received the drug.

Looking for a breakthrough

"The biggest disappointment from this trial, was that if we had shown benefit with a drug like bapi, it would give people hope that Alzheimer's is a treatable disease, that we can slow it down," Salloway said.

That much needed breakthrough could come from new trials that apply the lessons researchers learned. It is likely that many of the participants, for example, had some form of dementia other than Alzheimer's disease, Salloway said. A future trial should only include those with amyloid buildup confirmed by a PET scan and spinal fluid testing.

"We were surprised to find that overall 20 percent of participants in both the bapi and solanezumab trials did not meet the threshold for amyloid buildup," Salloway said. "That proportion was higher for ApoE4 noncarriers."

Also amyloid plays a more critical role early in the development of the disease, he said. Trials that administer the medication earlier could produce greater effects.

It would make sense, he said, to pair drugs like bapi with drugs such as a beta secretase inhibitor that maximize amyloid lowering. The safety of such a combination, or combination with drugs that address the tangles of tau proteins also found in Alzheimer's, is not known, Salloway said, but needs to be carefully tested.

"Without taking strategic risks, we aren't going to make the progress we need to move forward," he said.

Testing drug combinations, however, may require pharmaceutical companies to pool resources and share data. He acknowledged that's something competitors are usually reluctant to do. These partnerships are forming in the pre-competitive arena, he said, but need to be expanded into clinical trials.

"For the level of suffering with this disease and for our economy, we have to break down barriers and come up with innovative approaches."

Provided by Brown University

Forget about forgetting: The elderly know more and use it better

What happens to our cognitive abilities as we age? If your think our brains go into a steady decline, research reported this week in the journal Topics in Cognitive Science may make you think again. The work, headed by Dr. Michael Ramscar of Tübingen University, takes a critical look at the measures usually thought to show that our cognitive abilities decline across adulthood. Instead of finding evidence of decline, the team discovered that most standard cognitive measures, which date back to the early twentieth century, are flawed. "The human brain works slower in old age," says Ramscar, "but only because we have stored more information over time."

22 jan 2014--Computers were trained, like humans, to read a certain amount each day, and to learn new things. When the researchers let a computer "read" only so much, its performance on cognitive tests resembled that of a young adult. But if the same computer was exposed to the experiences we might encounter over a lifetime – with reading simulated over decades – its performance now looked like that of an older adult. Often it was slower, but not because its processing capacity had declined. Rather, increased "experience" had caused the computer's database to grow, giving it more data to process – which takes time.

Technology now allows researchers to make quantitative estimates of the number of words an adult can be expected to learn across a lifetime, enabling the Tübingen team to separate the challenge that increasing knowledge poses to memory from the actual performance of memory itself. "Imagine someone who knows two people's birthdays and can recall them almost perfectly. Would you really want to say that person has a better memory than a person who knows the birthdays of 2000 people, but can 'only' match the right person to the right birthday nine times out of ten?" asks Ramscar.

The answer appears to be "no." When Ramscar's team trained their computer models on huge linguistic datasets, they found that standardized vocabulary tests, which are used to take account of the growth of knowledge in studies of ageing, massively underestimate the size of adult vocabularies. It takes computers longer to search databases of words as their sizes grow, which is hardly surprising but may have important implications for our understanding of age-related slowdowns. The researchers found that to get their computers to replicate human performance in word recognition tests across adulthood, they had to keep their capacities the same. "Forget about forgetting," explained Tübingen researcher Peter Hendrix, "if I wanted to get the computer to look like an older adult, I had to keep all the words it learned in memory and let them compete for attention."

The research shows that studies of the problems older people have with recalling names suffer from a similar blind spot: there is a far greater variety of given names today than there were two generations ago. This cultural shift toward greater name diversity means the number of different names anyone learns over their lifetime has increased dramatically. The work shows how this makes locating a name in memory far harder than it used to be. Even for computers.

Ramscar and his colleagues' work provides more than an explanation of why, in the light of all the extra information they have to process, we might expect older brains to seem slower and more forgetful than younger brains. Their work also shows how changes in test performance that have been taken as evidence for declining cognitive abilities in fact demonstrates older adults' greater mastery of the knowledge they have acquired.

Take "paired-associate learning," a commonly used cognitive test that involves learning to connect words like "up" to "down" or "necktie" to "cracker" in memory. Using Big Data sets to quantify how often different words appear together in English, the Tuebingen team show that younger adults do better when asked to learn to pair "up" with "down" than "necktie" and "cracker" because "up" and "down" appear in close proximity to one another more frequently. However, whereas older adults also understand which words don't usually go together, young adults notice this less. When the researchers examined performance on this test across a range of word pairs that go together more and less in English, they found older adult's scores to be far more closely attuned to the actual information in hundreds of millions of words of English than their younger counterparts.

As Prof. Harald Baayen, who heads the Alexander von Humboldt Quantitative Linguistics research group where the work was carried out puts it, "If you think linguistic skill involves something like being able to choose one word given another,younger adults seem to do better in this task. But, of course, proper understanding of language involves more than this. You have also to not put plausible but wrong pairs of words together. The fact that older adults find nonsense pairs – but not connected pairs – harder to learn than young adults simply demonstrates older adults' much better understanding of language. They have to make more of an effort to learn unrelated word pairs because, unlike the youngsters, they know a lot about which words don't belong together."

The Tübingen research conclude that we need different tests for the cognitive abilities of older people – taking into account the nature and amount of information our brains process. "The brains of older people do not get weak," says Michael Ramscar. "On the contrary, they simply know more."

More information: Michael Ramscar, Peter Hendrix, Cyrus Shaoul, Petar Milin, Harald Baayen. (2014) The Myth of Cognitive Decline: Non-Linear Dynamics of Lifelong Learning. Topics in Cognitive Science, 6, 5-42.onlinelibrary.wiley.com/doi/10.1111/tops.12078/full

Provided by Universitaet Tübingen

Here comes the sun: How vitamin D relaxes blood vessels

The sun in the mountains allows the body to produce vitamin D in winter. Credit: Heike Hochhauser/Vetmeduni Vienna

It's not just your mood that the dark months of winter can influence. Low levels of sunlight also mean lower levels of vitamin D in the body. Vitamin D deficiency can trigger a range of diseases but until recently little was known about the exact biological mechanisms behind this. A research team at the University of Veterinary Medicine, Vienna has now decrypted one of these unknown molecular mechanisms. Vitamin D regulates the elasticity of blood vessels and thus also affects blood pressure amplitude. The results were published earlier this year in the journal Molecular Endocrinology.

21 jan 2014--UV-B radiation in sunlight is the most important factor for the production of vitamin D, and that is why many people suffer from low levels of vitamin D during the winter months. Although certain foods do contain vitamin D, it is not usually possible to get an adequate supply of the vitamin from food. Many clinical studies have indicated that low vitamin D levels are related to cardiovascular disease such as high blood pressure, but also other diseases such as diabetes mellitus, autoimmune diseases and even cancer. However, the underlying molecular mechanisms were unclear.

Vitamin D deficiency leads to stiffening of the blood vessels

The two primary authors, molecular biologist Olena Andrukhova and medical doctor Svetlana Slavic, of the Institute of Physiology, Pathophysiology and Biophysics at the Vetmeduni Vienna, found that prolonged vitamin D deficiency can stiffenblood vessels. Examining the aorta, an elastic blood vessel that expands with each pulse of blood and then constricts again, the researchers showed that vitamin D deficiency makes the vessel less flexible. Andrukhova explains in detail: "Vitamin D enhances the production of the enzyme eNOS (endothelial nitric oxide synthase) in the inner layer of blood vessels, the endothelium. This is critical for the regulation of blood pressure. The enzyme produces a molecule called nitric oxide (NO), an important factor for the relaxation of smooth muscles in the blood vessels. When too little NO is formed, the vessels become less flexible. This ultimately leads to higher blood pressure which can give rise to other circulatory diseases. So indirectly, vitamin D controls blood pressure."

Co-author Slavic continues: "Stiffness of the blood vessels generally increases with age. Blood pressure amplitude thus tends to increase with age and leads to structural changes in the aorta. Elasticity deteriorates, and prolonged vitamin D deficiency can accelerate this process."

Simulation of vitamin D deficiency in mice

The scientists worked with genetically modified mice to explore the details of the mechanism. The vitamin D receptors in the animals were changed so that no vitamin D signalling was possible. Vitamin D also regulates the body's calcium and phosphate balance, so the rodents were given a special diet to ensure that they had enough calcium and phosphorus. The lack of vitamin D was therefore the only deficiency that could have affected the physiology of the animals.

After about a year without vitamin D signalling, the mice had increased blood pressure amplitude. The researchers conducted a series of studies on various tissues from the animals. To understand what lies behind the increased blood pressure amplitude, they focused particularly on the aorta and found decreased expression of eNOS, increased deposition of collagen and fewer elastic fibres. Over time, the blood vessels had become more rigid and less able to adapt flexibly to the volume of blood streaming through them. The consequence was increased blood pressure amplitude and changes in cardiac structure and function. In future studies, the researchers want to examine whether vitamin D affects different cell types in blood vessels in different ways.

Refuelling light for the heart and the circulation

In Europe, it has often been considered to enrich certain foods with vitamin D, as is customary in the United States, for example. However, an external source of vitamin D also carries risks since any excess vitamin D cannot be excreted by the body. When used at very high doses it can lead to calcium deposits in blood vessels, kidneys, lungs and the heart. However, a lack of vitamin D can also have dramatic consequences. Institute board Professor Reinhold Erben states: "It is not that vitamin D deficiency will lead immediately to an increase in blood pressure amplitude or blood pressure, but over the long term it can lead to cardiovascular damage. Vitamin D is the chemical translation of the sun in our bodies and we should stock up on a regular basis, especially in winter. We have to remember that in Central Europe, vitamin D synthesis in the skin is physically impossible from November to February at sea level. Levels of UV-B radiation are just too low. The alternatives are vitamin D supplements or a stay in the mountains."

More information: "Vitamin D Is a Regulator of Endothelial Nitric Oxide Synthase and Arterial Stiffness in Mice." Olena Andrukhova, Svetlana Slavic, Ute Zeitz, Sabine C. Riesen, Monika S. Heppelmann, Tamas D. Ambrisko, Mato Markovic, Wolfgang M. Kuebler, and Reinhold G. Erben. Molecular Endocrinology 2014 28:1, 53-64. DOI: dx.doi.org/10.1210/me.2013-1252

Provided by University of Veterinary Medicine -- Vienna