Why does maximum heart rate drop with age?

Researchers at the University of Colorado have new insight into the age-old question of why maximum heart rate (maxHR) decreases with age. This decrease in maxHR not only limits the performance of aging athletes but it is also a leading cause for nursing home admittance for otherwise-healthy elderly individuals who no longer have the physical capacity required for independent living. We say we're just getting old and slowing down, but exactly what is it that is slowing down?

15 oct 2013--Everybody knows that aerobic capacity decreases with age. You know that chart in your gym that shows your target heart rate decreasing as you get older? Well, that's not a senior discount to let the elderly get off easy on their treadmill workouts. It's because older hearts simply can't beat as fast as younger hearts. So the older person who's doing 120 beats per minute is probably working harder—at a higher percentage of maximum heart rate—than the younger person who is at 150 beats per minute.

A new study by a group led by Catherine Proenza, PhD and Roger Bannister, PhD from the University of Colorado School of Medicine reports that one of the reasons for the age-dependent reduction in maximum heart rate is that aging depresses the spontaneous electrical activity of the heart's natural pacemaker, the sinoatrial node.

A dissertation from Eric D. Larson, a graduate from Proenza's lab in the Department of Physiology and Biophysics, is described in the article. Larson said, "I utilized a method to record ECGs from conscious mice and found that maximum heart rate was slower in older mice, just as it is in older people. This result wasn't unexpected. But what was completely new was that the slower maxHR was because the individual pacemaker cells—called sinoatrial myocytes, or 'SAMs'—from old mice just couldn't beat as fast as SAMs from young mice."

The researchers recorded the tiny electrical signals from the isolated cells and found that SAMs from old mice beat more slowly, even when they were fully stimulated by the fight-or-flight response which can be observed in these individual cells. The slower beating rate was due to a limited set of changes in the action potential waveform, the electrical signal that is generated by the cells. The changes were caused by altered behavior of some ion channels in the membranes of the older cells. (Ion channels are proteins that conduct electricity across the cell membrane. Imagine a balloon with little tiny pinholes that open and close to let the air in and out; ion channels are like the pinholes.)

Like most initial discoveries in basic science, this study opens many more questions and avenues for further research. But the significance of the study is that it raises the possibility that sinoatrial ion channels and the signaling molecules that regulate them could be novel targets for drugs to slow the loss of aerobic capacity with age. In the meanwhile, Proenza notes that "although maximum heart rate goes down for everybody equally, regardless of physical conditioning, people can improve and maintain their aerobic capacity at all ages by exercising."

This study will be published in the Oct. 14 Proceedings of the National Academy of Sciences.

More information: Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate, www.pnas.org/cgi/doi/10.1073/pnas.1308477110

Provided by University of Colorado Denver

Meta-analysis indicates widespread use of vitamin D supplements to prevent osteoporosis in healthy adults unjustified

Taking vitamin D supplements does not improve bone mineral density at the total hip, spine, forearm, or in the body as a whole, a large meta-analysis involving more than 4,000 healthy adults published in The Lancet has found. With close to half of adults aged 50 and older using vitamin D supplements, the authors conclude that continuing widespread use of these supplements to prevent osteoporosis in healthy adults is needless.

14 oct 2013--"Most healthy adults do not need vitamin D supplements", explains study leader Professor Ian Reid from the University of Auckland in New Zealand. "Our data suggest that the targeting of low-dose vitamin D supplements only to individuals who are likely to be deficient could free up substantial resources that could be better used elsewhere in healthcare."

Reid and colleagues from the University of Auckland conducted a systematic review and meta-analysis of all randomised trials examining the effects of vitamin D supplementation on bone mineral density in healthy adults up to July 2012.

Analysis of data from 23 studies involving 4082 healthy adults (average age 59 years) did not identify any effects for people who took vitamin D for an average period of 2 years, apart from a small but statistically significant increase in bone density (0.8%) at the femoral neck. According to the authors, such a localised effect is unlikely to be clinically significant.

The authors conclude, "This systematic review provides very little evidence of an overall benefit of vitamin D supplementation on bone density…Continuing widespread use of vitamin D for osteoporosis prevention in community-dwelling adults without specific risk factors for vitamin D deficiency seems to be inappropriate."

Writing in a linked Comment, Clifford J Rosen from the Maine Medical Research Institute in the USA discusses how our recent understanding of vitamin D lends support to these findings, confirming that, "Supplementation to prevent osteoporosis in healthy adults is not warranted. However, maintenance of vitamin D stores in the elderly combined with sufficient dietary calcium intake (800–1200 mg per day) remains an effective approach for prevention of hip fractures."

More information: www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61647-5/abstract

Provided by Lancet

Psychological interventions halve deaths and CV events in heart disease patients

Psychological interventions halve deaths and cardiovascular events in heart disease patients, according to research from Athens, Greece, presented at the Acute Cardiac Care Congress 2013.

13 oct 2013--The Acute Cardiac Care Congress 2013 is the annual meeting of the Acute Cardiovascular Care Association (ACCA) of the European Society of Cardiology (ESC). It takes place 12-14 October in Madrid, Spain.

Dr Zoi Aggelopoulou, a nurse and one of the study authors, said: "The nurses on our coronary care unit observed that patients were less likely to have another heart attack, die, or return to hospital when we talked to them about their treatment, played music for them or helped religious patients to say prayers. It made us think that coronary heart disease is not just physical but also has a psychological component."

She added: "We wanted to find out if others had observed the same thing, and whether psychological support had a real impact on the outcomes of patients with coronary heart disease."

The current study was a meta-analysis of 9 randomised controlled trials. The researchers evaluated whether psychological interventions could improve outcomes of patients with coronary heart disease when combined with a conventional rehabilitation programme.

The researchers found that the addition of psychological interventions reduced mortality and cardiovascular events by 55% after 2 years or more.

Dr Aggelopoulou said: "We found a huge benefit of psychological interventions after 2 years, with less patients dying or having a cardiovascular event and therefore fewer repeat hospital visits. The interventions included talking to patients and their families about issues that were worrying them, relaxation exercise, music therapy, and helping them to say prayers."

She added: "Patients want to know what will happen to them when they leave hospital, whether or not they can have sex, and how to take their medication. Our research shows that giving them information and providing reassurance decreases the chances of them dying or having another heart attack. Patients can help instigate this new culture of information by asking more questions and getting more involved in decisions about their treatment."

Population-based studies have shown that psychological factors may have an influence on the likelihood of having a heart attack in the first place. The factors include depression, social isolation, low socioeconomic status, and chronic stress such as occupational or marital distress and stress from caregiving.

Dr Aggelopoulou said: "The results of our study strengthen the evidence that psychological factors have a big role to play in heart disease. Not only do they impact on the risk of having a heart attack, but they also affect the future outlook of a patient who has had a cardiovascular event. This validates our view that cardiovascular disease is not just a physical disease but also has a substantial psychological component."

The researchers concluded that psychological interventions should be incorporated into the rehabilitation of patients with coronary heart disease. Dr Aggelopoulou said: "More clinical trials are needed to clarify which interventions are most effective and how they can best be implemented."

She concluded: "We can help our patients by simply talking to them or introducing new things like music therapy into our clinical practice. Coronary units are busy places – in Greece we sometimes have 1-2 nurses for 10-20 patients in the coronary care unit and we are under time pressure. But our finding that the addition of psychological support on top of physiological therapies reduces death and cardiovascular events by 55% should be a wake-up call that these interventions really do work. Preventing repeat hospital visits would free up the time we need to implement them."

Provided by European Society of Cardiolog

New research suggests that high dietary intake of polyphenols are associated with longevity

It is the first time that a scientific study associates high polyphenols intake with a 30% reduction in mortality in older adults. The research, published on Journal of Nutrition, is the first to evaluate the total dietary polyphenol intake by using a nutritional biomarker and not only a food frequency questionnaire.

Polyphenols: diet improves health

12 oct 2013--Polyphenols are naturally occurring compounds found largely in fruits, vegetables, coffee, tea, nuts, legumes and cereals. More than 8,000 different phenolic compounds have been identified in plants. Polyphenols have antioxidant, antiinflammatory, anticarcinogenic, etc. effects.

The research published on Journal of Nutrition is based on a 12-year follow-up of a population sample composed by 807 men and women aged 65 or over from Greve and Bagno (Tuscany, Italy), within the InCHIANTI study. The group of the UB analysed the effect of polyphenol-rich diets by means of a nutritional biomarker —the total urinary polyphenol (TUP) concentration— as a proxy measure of intake. To be exact, UB researchers contributes to first literature references on TUP application to epidemiological or clinical studies.

New biomarkers for nutritional studies

Professor Cristina Andrés Lacueva, head of the Biomarkers and Nutritional & Food Metabolomics Research Group of the UB and coordinator of the study, explains that "the development and use of nutritional biomarkers enables to make a more precise and, particularly, more objective estimation of intake as it is not only based on participants' memory when answering questionnaire. Nutritional biomarkers take into account bioavailabity and individual differences. According to the expert, "this methodology makes a more reliable and accurate evaluation of the association between food intake and mortality or disease risk".

In conclusion, the research proves that overall mortality was reduced by 30% in participants who had rich-polyphenol diets (>650 mg/day) in comparison with the participants who had low-polyphenol intakes (<500 day="" mg="" p="">

Raúl Zamora Ros, first author of the study, points out that "results corroborate scientific evidence suggesting that people consuming diets rich in fruit and vegetables are at lower risk of several chronic diseases and overall mortality". Moreover, the research stresses the importance of evaluating —if possible— food intake by using nutritional biomarkers, not only food frequency questionnaires.

The Biomarkers and Nutritional & Food Metabolomics Research Group, which participates in the project Fun-C-Food (Consolider Ingenion), collaborates actively with several national and international research groups. It focuses its activity on the analysis of new more effective and sensitive nutritional biomarkers based on the bioavailabilty of bioactive compounds in food and their activity, in order to associate the intake of certain foods (consumption markers) with their potential effects on people's health.

More information: Zamora, R. et al. High concentrations of a urinary biomarker of polyphenol intake are associated with decreased mortality in older adults, Journal of Nutrition, June 2013. PMID: 23803472

Provided by University of Barcelona

Lab mice breakthrough offers Alzheimer's hope

Scientists say they have developed a drug which could be used to treat Alzheimer's, Parkinson's and other brain disorders

Scientists on Thursday said they had tested a drug that in mice prevented the death of brain cells, boosting hopes in the fight against Alzheimer's, Parkinson's and other neurodegenerative diseases.

11 oct 2013--Still at a very early and experimental stage, the drug blocks disruption of a defence system in the brain which plays a common role in these tragic disorders.

Many brain diseases start with the buildup of rogue, scrunched-up proteins, or amyloids.

The organ's response to this is to switch on a defence mechanism called the unfolded protein response, or UPR.

The mechanism orders cells to stop producing new proteins so that the problem is not worsened.

But the buildup of misshapen proteins prevents the UPR mechanism from being switched off.

As a result, the misshapen proteins are no longer made—but nor are normal proteins that are essential for brain-cell survival. Neurons start to die, are not replenished, and the disease progresses.

British researchers, reporting in the US journal Science Translational Medicine, tested a drug that works on a key point in this switching pathway, an enzyme called PERK, to keep protein production open.

Known by its lab name as GSK2606414—it is made by British drugmaker GlaxoSmithKline—the orally-administered drug was tested on 29 mice with prion disease, a family of disorders that includes Creuzfeldt-Jakob disease.

These were compared against a group of "control" mice, whose brain had also been infected with prions but which did not receive the drug.

Mice that were treated seven weeks after being infected with the prions suffered no memory loss in a test to recognise a familiar object, but those treated at nine weeks lost their memory.

The mice were killed and autopsied, and examination of samples under a microscope confirmed that brain-cell death among all the treated mice was very low, although less so among the nine-week group.

The University of Leicester team say they are hugely buoyed by the success, although many more years of tests lie ahead.

"We were extremely excited when we saw the treatment stop the disease in its tracks and protect brain cells, restoring some normal behaviours and preventing memory loss in the mice," said Giovanna Mallucci, a professor of toxicology.

"We're still a long way from a usable drug for humans - this compound had serious side effects," Mallucci told Britain's Press Association.

"But the fact we have established that this pathway can be manipulated to protect against brain cell loss, first with genetic tools and now with a compound, means that developing drug treatments targeting this pathway for prion and other neurodegenerative diseases is now a real possibility."

If the drug eventually progressed to human patients, people would need treatment "for years or even decades in many cases," the study also cautioned.

In a commentary carried in the same journal, neuroscientists Wiep Scheper and Jeroen Hoozemans of the Free University of Amsterdam said the research may have thrown open "a new therapeutic strategy."

They too were prudent.

They said mouse models designed to replicate human brain disease had limitations, and in humans, loss of the PERK enzyme also had side-effects in promoting diabetes and skeletal defects.

Eric Karran, director of research at the British charity Alzheimer's Research UK, said the idea of a single drug to target a mechanism shared by a range of diseases was compelling.

"But this compound is still at an early stage. It will be important for these findings to be repeated and tested in models of other neurodegenerative diseases, including Alzheimer's disease," he said in a statement.

"(...) What is true in animals does not always hold true in people and the ultimate test for this compound will be to see whether it is safe and effective in people with these diseases."

Alzheimer's is the commonest form of dementia, a condition that afflicts nearly 35.6 million people around the globe, according to the World Health Organisation (WHO).

This number is expected to reach 65.7 million by 2030 and 115.4 million by 2050.

Treating and caring for people with dementia currently costs the world more than $600 billion (440 billion euros) per year, the WHO says.

More information: "An Oral Treatment Targeting the Unfolded Protein Response Prevents Neurodegeneration and Clinical Disease in Prion-Infected Mice," by J.A. Moreno et al. Science Translational Medicine, 2013.

"A New PERKspective on Neurodegeneration," by W. Scheper et al. Science Translational Medicine, 2013.

New study links depression in newly diagnosed Parkinson's disease patients to reduced striatal dopamine synthesis

According to the Parkinson's Disease Foundation, up to 60% of individuals with Parkinson's disease (PD) exhibit mild to moderate depression, which is often underdiagnosed. It is unclear whether depression results from having a debilitating disease or reflects a parallel abnormal change in the brain caused by PD pathophysiology.

10 oct 2013--One hypothesis is that depression in PD may reflect impaired striatal dopamine function, but previous investigations have produced contradictory results. By scanning the brains of newly diagnosed patients not yet taking PD medications, Finnish investigators have shown that the level of depression is inversely related to the ability to synthesize dopamine in the striatum and the effect is seen only in the left striatum. Their results are published in the latest issue of the Journal of Parkinson's Disease.

Depression in Parkinson's patients can reduce quality of life and impede daily activities, and those with depressive symptoms tend to begin medications for motor symptoms earlier than those who are not depressed. Treating depression can improve both quality of life and movement, and medications such as dopamine agonists have antidepressant effects in PD patients.

In the current report, investigators used 18fluorodopa PET scans to look at two different groups of PD patients. One group consisted of 15 de novo patients, meaning that the patients were newly diagnosed with PD and that they had never been treated with PD medications such as levodopa. The average PD disease duration for this group was less than 5 years. Two of these patients were diagnosed with clinical depression.

In the unmedicated PD group, the authors found significant negative correlations between symptoms of depression (as measured by the Beck Depression Inventory (BDI)) and dopamine synthesis capacity (as measured by FDOPA uptake) in the left striatum (putamen p=0.002, caudate p=0.042). No significant correlations were observed in the right striatum. Neither the severity nor side of motor symptoms affected the findings.

Different results were found in a group of 20 patients with moderate disease severity who were already being treated with PD medications. The average duration of disease for these patients was 5.6 years and 90% were using levodopa, 90% a dopamine agonist, and 60% a MAO-B inhibitor. Ten percent were also on an antidepressant. In this group, no significant correlations were found between BDI scores and regional FDOPA uptake in the caudate or putamen.

"Previous studies looking at depression and striatal dopamine synthesis capacity using 18Ffluorodopa PET scanning yielded inconsistent results, most likely reflecting marked heterogeneity in patients' disease severity and medication history," says lead investigator Juho Joutsa, MD, of the Division of Clinical Neurosciences at Turku University Hospital and University of Turku in Finland. "The results should be interpreted to indicate a link between mood and dopamine, which can be observed in early-stage unmedicated patients, but the relationship may also be present, but masked, in more advanced patients."

The study was the first using 18fluorodopa PET scanning technology to show that depression was associated with reduced dopamine synthesis capacity only on the left side. However, Dr. Joutsa comments that studies using dopamine transporter ligands have also reported a similar lateralization of effect.

PD is the second most common neurodegenerative disorder in the United States, affecting approximately one million Americans and five million people worldwide. Its prevalence is projected to double by 2030. The most obvious symptoms are movement-related, such as involuntary shaking and muscle stiffness. Non-motor symptoms, such as worsening depression, anxiety, and sleep disturbances, can appear prior to the onset of motor symptoms.

More information: Joutsa, J. et al. Reduced Striatal Dopamine Synthesis Capacity is Associated with Symptoms of Depression in Patients with de novo Unmedicated Parkinson's Disease, Journal of Parkinson's Disease, Volume 3/Issue 3. DOI: 10.3233/JPD-130205

Provided by IOS Press

'Cyberchondria' from online health searches is worse for those who fear the unknown

Turning to the Internet to find out what ails you is common, but for folks who have trouble handling uncertainty, "cyberchondria" – the online counterpart to hypochondria – worsens as they seek answers, a Baylor University researcher says.

09 oct 2013--"If I'm someone who doesn't like uncertainty, I may become more anxious, search further, monitor my body more, go to the doctor more frequently—and the more you search, the more you consider the possibilities," said Thomas Fergus, Ph.D., an assistant professor of psychology and neuroscience in Baylor's College of Arts & Sciences. "If I see a site about traumatic brain injuries and have difficulties tolerating uncertainty, I might be more likely to worry that's the cause of the bump on my head."

His study is published in the journal Cyberpsychology, Behavior and Social Networking.

As if fearing a catastrophic disease or injury isn't bad enough, doubts about health—unfounded or not—can trigger worries about potential medical bills, disability and job loss, he said. And that can lead to even more Googling, obsessing, doctor visits, unnecessary medical testing and distress.

Prior research shows that approximately eight of 10 American adults seek medical information on the Internet.

Fergus sampled 512 healthy adults, with a mean age of 33.4 years. Fifty-five percent were women, 59 percent had at least a two-year degree, 53 percent worked at least 20 hours weekly, and 67 percent were unmarried.

He used several measures, among them a scale in which people assessed such statements as "I always want to know what the future has in store for me"; a health anxiety inventory, in which—regardless of their actual health—they responded to such statements as "I spend most of my time worrying about my health"; and a scale assessing how searches for online health information affected respondents' anxiety.

While fearing the worst when it comes to health is not new, the online glut of medical information – some of it from questionable sources – may be more disturbing than that contained in medical manuals that people consult or obtain directly from a doctor, Fergus said.

"When you look at a medical book, you might not see all the possibilities at once, but online you're presented with so many," he said.

Provided by Baylor University

Life in a bubble: Nobel secrets of body's cell transport system

A portrait of US scientist Randy W Schekman and drafts of his work are displayed on a screen during a press conference to announce the winners of the 2013 Nobel Prize in medicine on October 7, 2013 in Stockholm

08 oct 2013--Vesicles, the bubble-shaped vessels that transport molecules within cells, may hold the secret to halting viruses or even combating Alzheimer's, say experts who hailed Monday's Nobel awarded to three leaders in the field.

Thousands of these sac-like cargo vehicles reside in every human cell.

Their job is to transport molecules within and between cells.

Vesicles are crucial for the very functioning of cells—shipping everything from neurotransmitter molecules responsible for signalling in the brain to hormones and immune responses to viral intruders.

When things go well, the vesicles are like trucks providing just-in-time delivery of parts for a factory buzzing with activity.

But if vesicles arrive too late or too early, or go to the wrong place, they can cause the cell to malfunction—a potential trigger for disease. They also allow viruses to propagate by transporting viral proteins within cells.

"Very fundamental processes in life depend on vesicular transport," Dick Hoekstra, cell biology professor at the University of Groningen in the Netherlands, told AFP.

"All organelles (compartments) within a cell are communicating with each other via vesicles," he said. "The way that viruses reproduce is also very much dependent on the vesicular transport system."

Inside cells is a hive of machinery that cranks out proteins, the molecules that sustain the cell and enable it to function, but also help it work with other cells.

Most molecules produced by cells are too large to pass through cell membranes and thus are transported instead by vesicles.

The vesicles are coated with fatty membranes that "fuse" with the membranes on other vesicles, to pass on their cargo, a bit like water drops merging on a window pane.

They are able to identify their destination thanks to an "address code" of proteins studding the membrane. The proteins are like the matching sides of a zip: when they fit, two vesicles merge and the cargo is transferred.

"Its almost like a bubble hitting a wall and the contents of that bubble are then released," explained Mike Cousins, chairman of neuronal cell biology at Edinburgh University.

Each vesicle is about 50 nanometres (billionths of a metre) in diameter and transfers about a million molecules at a time.

Vesicles continually "bud off" from one cell membrane, bulging out to fuse to another, then releasing their precious, molecular cargo.

The three men honoured by the Nobel Assembly on Monday, US duo James Rothman and Randy Schekman and German-born Thomas Suedhof, have put decades of work into shedding more light on how vesicles work—and why, sometimes, they do not.

Schekman figured out which genes were responsible for mixing up the transport system, which can cause vesicles to pile up in parts of the cell like a traffic jam.

Rothman discovered that a protein complex enables vesicles to dock and fuse.

Suedhof took the work further by showing more precisely how the protein "zipper" opens up to allow neurotransmitters to move between nerve cells in the brain.

The knowledge has helped us understand the important role that vesicles may be playing in diseases like diabetes and immune disorders.

"In the last five years it is looking like presynaptic disfunction, messed-up vesicle transport, is underlying a lot of potential neurodevelopmental disorders like... autism," said Cousins.

"There is also accumulating evidence that it is going to be very important in neurodegenerative diseases: Alzheimer's disease, Parkinson's disease."

Hoekstra said better understanding of vesicles may also benefit other medical fields: his department is researching vesicle-like ways of bypassing the so-called blood-brain barrier, a circulatory cut-off between blood flow to the brain and the rest of the body, to make it easier for doctors to administer drugs to the organ.

Key cellular auto-cleaning mechanism mediates the formation of plaques in Alzheimer's brain

Aβ plaque formation depends on autophagy. Immunohistological analysis of Aβ plaque of 20-month-old APP and Atg7flox/flox; CamKII-Cre x APP mouse brains. Credit: Per Nilsson, RIKEN

Autophagy, a key cellular auto-cleaning mechanism, mediates the formation of amyloid beta plaques, one of the hallmarks of Alzheimer's disease. It might be a potential drug target for the treatment of the disease, concludes new research from the RIKEN Brain Science Institute in Japan. The study sheds light on the metabolism of amyloid beta, and its role in neurodegeneration and memory loss.

06 oct 2013--In a study published today in the journal Cell Reports, Drs. Per Nilsson, Takaomi Saido and their team show for the first time using transgenic mice that a lack of autophagy in neurons prevents the secretion of amyloid beta and the formation of amyloid beta plaques in the brain. The study also reveals that an accumulation of amyloid beta inside neurons is toxic for the cells.

Alzheimer's disease, the most common form of dementia, affects nearly 36 million people worldwide, and this number is set to double over the next 20 years. However, the causes of the disease are not well understood and no disease-modifying treatment is available today.

Patients with Alzheimer's disease have elevated levels of the peptide amyloid beta in their brain and amyloid beta plaques form outside their neurons. This accumulation of amyloid beta causes the neurons to die, but until now the underlying mechanism remained a mystery. And whether the elevated levels of the peptide inside or outside the cells are to blame was unknown.

Autophagy is a cellular cleaning mechanism that normally clears any protein aggregates or other 'trash' within the cells, but that is somewhat disturbed in Alzheimer's patients.

Autophagy mediates Aβ secretion. wt and autophagy-deficient Atg7flox/flox; Nes-Cre primary neurons expressing APP were stained for Aβ. Credit: Per Nilsson, RIKEN

To investigate the role of autophagy in amyloid beta metabolism, Nilsson et al. deleted an important gene for autophagy, Atg7, in a mouse model of Alzheimer's disease. Contrary to what they were expecting, their results showed that a complete lack of autophagy within neurons prevents the formation of amyloid beta plaque around/outside the cells. Instead, the peptide accumulates inside the neurons, where it causes neuronal death, which in turn leads to memory loss.

This is a graphical overview depicting the role of autophagy in Aβ secretion from neurons. Credit: Per Nilsson, RIKEN

"Our study explains how amyloid beta is secreted from the neurons, via autophagy, which wasn't well understood," comments Dr Nilsson. "To control amyloid beta metabolism including its secretion is a key to control the disease. Autophagy might therefore be a potential drug target for the treatment of Alzheimer's disease," he adds.

More information: Nilsson et al., "Ab Secretion and Plaque Formation Depend on Autophagy" Cell Reports (2013) DOI: 10.1016/j.celrep.2013.08.042

Provided by RIKEN

Depression may increase your risk of Parkinson's disease

People who are depressed may have triple the risk of developing Parkinson's disease, according to a study published in the October 2, 2013, online issue of Neurology, the medical journal of the American Academy of Neurology.

05 oct 2013--"Depression is linked in other studies to illnesses such as cancer and stroke," said study author Albert C. Yang, MD, PhD, with Taipei Veterans General Hospital in Taipei, Taiwan. "Our study suggests that depression may also be an independent risk factor for Parkinson's disease."

Researchers analyzed the medical records of 4,634 people with depression and 18,544 free of depression over 10 years. They also looked at the risk of Parkinson's disease after excluding people who were diagnosed with Parkinson's disease within two or five years following their depression diagnosis.

During the 10-year follow-up period, 66 people with depression, or 1.42 percent, and 97 without depression, or 0.52 percent, were diagnosed with Parkinson's disease. People with depression were 3.24 times more likely to develop Parkinson's disease than those without depression.

"Many questions remain, including whether depression is an early symptom of Parkinson's disease rather than an independent risk factor for the disease," Yang said. "Our study also found that depression and older age and having difficult-to-treat depression were significant risk factors as well."

Provided by American Academy of Neurology

Resveratrol remains effective against cancer after the body converts it

A chemical found in red wine remains effective at fighting cancer even after the body's metabolism has converted it into other compounds. This is an important finding in a new paper published in the journal Science Translational Medicine by Cancer Research UK-funded researchers at the University of Leicester's Department of Cancer Studies and Molecular Medicine.

04 oct 2013--The paper reveals that resveratrol – a compound extracted from the skins of red grapes – is not rendered ineffective once it is metabolised by the body.

This is an important development, as resveratrol is metabolised very quickly – and it had previously been thought that levels of the extracted chemical drop too quickly to make it usable inclinical trials.

The new research shows that the chemical can still be taken into cells after it has been metabolised into resveratrol sulfates.

Enzymes within cells are then able to break it down into resveratrol again – meaning that levels of resveratrol in the cells are higher than was previously thought.

In fact, the results appear to show resveratrol may be more effective once it has been generated from resveratrol sulfate than it is if it has never been metabolised because the concentrations achieved are higher.

The team, led by University of Leicester translational cancer research expert Professor Karen Brown, administered resveratrol sulfate to mice models.

They were subsequently able to detect free resveratrol in plasma and a variety of tissues in the mice.

This is the first direct sign that resveratrol can be formed from resveratrol sulfate in live animals, and the researchers think it may help to show how resveratrol is able to have beneficial effects in animals.

The study also showed that resveratrol generated from resveratrol sulfate is able to slow the growth of cancer cells by causing them to digest their own internal constituents and stopping them from dividing.

Professor Karen Brown said: "There is a lot of strong evidence from laboratory models that resveratrol can do a whole host of beneficial things – from protecting against a variety of cancers and heart disease to extending lifespan.

"It has been known for many years that resveratrol is rapidly converted to sulfate and glucuronide metabolites in humans and animals – meaning the plasma concentrations of resveratrol itself quickly become very low after administration.

"It has always been difficult to understand how resveratrol is able to have activity in animal models when the concentrations present are so low, and it has made some people skeptical about whether it might have any effects in humans.

"Researchers have hypothesized for a long time that resveratrol might be regenerated from its major metabolites in whole animals but it has never been proven.

"Our study was the first to show that resveratrol can be regenerated from sulfate metabolites in cells and that this resveratrol can then have biological activity that could be useful in a wide variety of diseases in humans.

"Importantly, we did all our work with clinically achievable concentrations so we are hopeful that our findings will translate to humans.

"Overall, I think our findings are very encouraging for all types of medical research on resveratrol. They help to justify future clinical trials where, previously, it may have been difficult to argue that resveratrol can be useful in humans because of the low detectable concentrations.

"There is considerable commercial interest in developing new forms of resveratrol that can resist or overcome the issue of rapid metabolism. Our results suggest such products may not actually be necessary to deliver biologically active doses of resveratrol to people."

Dr Sarah Williams, Cancer Research UK health information officer, said: "This interesting study supports continued research into resveratrol as a therapeutic molecule, but it's important to note that any benefits from the molecule don't come from drinking red wine. It's well established that drinking any type of alcohol, including red wine, increases the risk of developing cancer."

More information: "Sulfate Metabolites Provide an Intracellular Pool for Resveratrol Generation and Induce Autophagy with Senescence," by K.R. Patel et al. Science Translational Medicine, 2013.

Provided by University of Leicester

First ever global 'index' to measure wellbeing of older people

A professor at the University of Southampton working with HelpAge International and an international expert group has developed the Global AgeWatch Index to help highlight the varying quality of life and wellbeing that older people experience in countries around the world.

03 oct 2013--With the support of the United Nations Fund for Population, Global AgeWatch Index 2013 is the first quantitative measure of its kind to focus on the wellbeing of older people on a worldwide scale. The Index compares the experiences of older people from 91 countries around the world and ranks them in order of quality of experience.

Professor Asghar Zaidi, from the Centre for Research on Ageing at Southampton, was consultant of the project commissioned by HelpAge International. He says: "The Global AgeWatch Index is the beginning of a process in which we are gathering all the available evidence of the lives of older people around the world.

"It follows the footsteps of the Human Development Index of the United Nations Development Programme (UNDP) and presents, in an accessible and engaging way, a 'dashboard'1 of indicators that measure the multidimensional quality of life and wellbeing of older people in a range of different socio-economic contexts."

The Index recognises that income, health, personal capabilities and an enabling social environment are all important aspects of the wellbeing of older citizens. By analysing national policies and strategies, it finds that:

• Sweden is the best place for older people.

• It is closely followed by Norway, with Japan the only non-European and non-North American country in the top 10.

• Mauritius is the top African country.

• Chile leads a cluster of Latin American countries that includes Uruguay, Argentina, Brazil, Costa Rica, Ecuador and Panama – which do well in the Index.

• The worst place for an older person is Afghanistan. Just above it come Pakistan, Tanzania and Jordan.

• The UK is ranked at 13, next to Ireland (12) and Australia (14) but five positions higher than France (18).

The Index focuses on older people's income security, health status, employment and education capabilities and the enabling environment of societies in which they live. It builds a strong case for better policies and services to improve their lives in many countries – especially in developing countries.

By 2050 the number of older people in the world will have risen to more than two billion and the Index, and the two reports based on it (co-authored by Prof Asghar Zaidi with HelpAge International staff), emphasise that such 'stock taking' work is absolutely essential in developing new ways to tackle the global challenge of population ageing and to empower older people to hold their leaders to account.

Silvia Stefanoni, Interim Chief Executive of HelpAge International, says: "The world is rapidly ageing: people over 60 years of age already exceed children under 5, and by 2050 they will outnumber children under 15. However, the continual exclusion of ageing from national and global agendas is one of the biggest obstacles to meeting the needs of the world's ageing population.

"By giving us a better understanding of the quality of life of women and men as they age, this new Index can help us focus our attention on where things are going well and where we have to make improvements."

Professor Zaidi from the University of Southampton adds: "We expect the Index to become an important research and analysis framework for practitioners and policy-makers alike, as it will facilitate cross-national comparative research on the quality of life and wellbeing of older people, and help identify data and knowledge gaps on issues of ageing. We need to give more and more importance to such data gathering work – in fact, since the lives of older people are at stake, we can't afford not to."

The Index does not simply demonstrate the best and worst places for people to grow old, but is also a tool to encourage countries to recognise the challenges of their ageing populations. It reveals some surprising global and regional comparisons and indicates Gross Domestic Product per capita, a proxy for country's wealth and standard of living, does not necessarily lead to better welfare outcomes for older people:

• The G20 economies are spread right across the full range of the Index.

• The fastest ageing G20 countries – India, Indonesia, Mexico, Russia and Turkey, where older populations are set to more than double over the next 40 years - are in the bottom half of the Index.

• The tremendous economic growth of the BRICS2 countries has not necessarily resulted in higher benefits for older people: Brazil and China rank relatively high in the Index, while India and Russia fare less well.

• Sri Lanka at 36 ranks much higher than its South Asian neighbour Pakistan, at 89, despite having similar levels of GDP - Sri Lanka scoring significantly higher on age-friendly environment.

Professor Zaidi and HelpAge International developed the Index in close consultation with an international, multidisciplinary advisory group that provided overall guidance on the concept, methodology and use of the Index. These experts represented United Nations agencies (such as UNFPA, UNDP, WHO, ILO3), as well as academic, civil society and other sectors with specialised knowledge on issues linked with ageing and wellbeing of older people.

The data used to construct the Index comes from the World Bank, World Health Organization, Institute for Health Metrics and Evaluation, International Labour Organization, and Gallup World Poll database.

Future work of the Global AgeWatch programme will include yearly updating of all the relevant data and also coverage of additional countries. A breakdown of data by gender is high on the agenda for future development of the Global AgeWatch Index, and there is also an aspiration that the Index will be extended to include a domain on political and civil rights of older people.

For an in-depth analysis of the Index results, including a table of overall country rankings (page 17), see the Insight Report, downloadable from: http://www.helpage.org/global-agewatch/ (a summary is available at: http://bit.ly/17Wt5ia )

For a detailed description of the methods, and the indicators used, see the Methodology Report, downloadable from: http://www.helpage.org/global-agewatch/

More information: 1 To interact with the Index 'dashboard', please visit: www.helpage.org/global-agewatch/

2 BRICS are five major emerging national economies: Brazil, Russia, India, China and South Africa

3 United Nations Population Fund, United Nations Development Programme, World Health Organisation, International Labour Organization

Provided by University of Southampton

Sleeping too little—or too much—associated with heart disease, diabetes, obesity

A new study by the Centers for Disease Control and Prevention (CDC) links too little sleep (six hours or less) and too much sleep (10 or more hours) with chronic diseases—including coronary heart disease, diabetes, anxiety and obesity—in adults age 45 and older. The American Academy of Sleep Medicine (AASM) encourages patients suffering from these common chronic conditions to speak with a sleep medicine physician who can evaluate their sleep patterns.

02 oct 2013--"It's critical that adults aim for seven to nine hours of sleep each night to receive the health benefits of sleep, but this is especially true for those battling a chronic condition," said Dr. M. Safwan Badr, president of the AASM. "Common sleep illnesses—including sleep apnea and insomnia—occur frequently in people with a chronic disease and can hinder your ability to sleep soundly. So if you're waking up exhausted, speak with a sleep physician to see if there's a problem. If you are diagnosed with a sleep illness, treating it could significantly improve disease symptoms and your quality of life."

"Some of the relationships between unhealthy sleep durations and chronic diseases were partially explained by frequent mental distress and obesity," said study co-author Janet B. Croft, PhD, senior chronic disease epidemiologist in CDC's Division of Population Health. "This suggests that physicians should consider monitoring mental health and body weight in addition to sleep health for patients with chronic diseases."

In the study, published in the October issue of the Journal Sleep, short sleepers reported a higher prevalence of coronary heart disease, stroke and diabetes, in addition to obesity and frequent mental distress, compared with optimal sleepers who reported sleeping seven to nine hours on average in a 24-hour period. The same was true for long sleepers, and the associations with coronary heart disease, stroke and diabetes were even more pronounced with more sleep.

"Sleeping longer doesn't necessarily mean you're sleeping well. It is important to understand that both the quality and quantity of sleep impact your health," said Badr. "A healthy, balanced lifestyle is not limited to diet and fitness; when and how you sleep is just as important as what you eat or how you exercise."

The study involved more than 54,000 participants age 45 or older in 14 states. Nearly one third of participants (31 percent) were identified as short sleepers, meaning they reported sleeping six hours or less on average. More than 64 percent were classified as optimal sleepers, and only 4 percent of participants were long sleepers.

More information: journalsleep.org/ViewAbstract.aspx?pid=29127

Provided by American Academy of Sleep Medicine

Extended follow-up of hormone therapy trials does not support use for chronic disease prevention

Extended follow-up of the two Women's Health Initiative hormone therapy trials does not support use of hormones for chronic disease prevention, although the treatment may be appropriate for menopausal symptom management in some women, according to a study in the October 2 issue of JAMA.

01 oct 2013--The hormone therapy trials of the Women's Health Initiative (WHI) were stopped after investigators found that the health risks outweighed the benefits. Menopausal hormone therapy continues in clinical use, but questions remain regarding its risks and benefits over the long-term for chronic disease prevention, according to background information in the article.

JoAnn E. Manson, M.D., Dr.P.H., of Brigham and Women's Hospital, Boston, and colleagues provide a comprehensive, integrated overview of findings from the two WHI hormone therapy trials with extended post-intervention follow-up and stratification by age and other important variables. The study included 27,347 postmenopausal women, ages 50 through 79 years, who were enrolled at 40 U.S. centers in 1993. Women with an intact uterus received conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) (n = 8,506) or placebo (n = 8,102). Women with prior hysterectomy received CEE alone (n = 5,310) or placebo (n = 5,429). The intervention lasted a median [midpoint] of 5.6 years in the CEE plus MPA trial, and 7.2 years in the CEE alone trial, with 6-8 additional years of follow-up until September 30, 2010.

The researchers found that overall, the risks of CEE+MPA during intervention outweighed the benefits. Risks were increased for coronary heart disease, breast cancer, stroke, pulmonary embolism, dementia (in women 65 years of age and older), gallbladder disease, and urinary incontinence. Benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Most risks and benefits dissipated postintervention, although some elevation in breast cancer risk persisted during follow-up.

For CEE in women with prior hysterectomy, the benefits and risks during the intervention phase were more balanced, with increased risks of stroke and venous thrombosis, reduced risk of hip and total fractures, and a nonsignificant reduction in breast cancer. Post-intervention with CEE, a significant decrease in breast cancer emerged and most other outcomes were neutral. For CEE alone, younger women (age 50-59 years) had more favorable results for all-cause death and heart attack.

Neither regimen affected all-cause mortality.

"In summary, current WHI findings based on results from the intervention, postintervention, and cumulative posttrial stopping phases do not support the use of either estrogen-progestin or estrogen alone for chronic disease prevention," the authors write.

"Even though hormone therapy may be a reasonable option for management of moderate to severe menopausal symptoms among generally healthy women during early menopause, the risks associated with hormone therapy, in conjunction with the multiple testing limitations attending subgroup analyses, preclude a recommendation in support of CEE use for disease prevention even among younger women. Current findings also suggest caution when considering hormone therapy treatment in older age groups, even in the presence of persistentvasomotor symptoms, given the high risk of coronary heart disease and other outcomes associated with hormone therapy use in this setting."

"Twenty-two years following its inception, the WHI is a model for publicly funded rigorous, thorough, and objective clinical trials that have broadly affected human health. More than 160,000 women participated (many with great pride), more than 900 peer-reviewed reports from the WHI Publications and Presentations Committee have been published, the WHI data set is publically available, and scores of trainees have been mentored in fields from human biology to public health by participating in its analysis. The WHI has overturned medical dogma regarding the use of menopausal hormone therapy," writes Elizabeth G. Nabel, M.D., of Brigham and Women's Hospital, Boston, in an accompanying editorial.

"The WHI underscores the decisive importance of taxpayer-funded research conducted by the National Institutes of Health (NIH). Further reductions in the NIH budget virtually ensure that vitally important studies like the WHI will not be conducted, and hence, U.S. society will be poorly served. The fact that the public sector undertook this historic project (and that the researchers whose work is now reported have taken it to its next stage) has moved medical science forward by the most effective means of doing so—shattering prior dogma. For that,women and all patients whose health depends on sound science are grateful."

More information: doi:10.l001/jama.2013.278040
doi:10.l001/jama.2013.278042

Provided by The JAMA Network Journals

Global study: World not ready for aging population

In this Sept. 26, 2013 photo, 80-year-old Marianne Blomberg works out at a gym in Stockholm. Much of the world is not prepared to support the ballooning population of elderly people, including many of the fastest-aging countries, according to a global study scheduled to be released Tuesday, Oct. 1, by the United Nations and an elder rights group. The Swedish government has suggested people continue working beyond 65, a prospect Blomberg cautiously welcomes but warns should not be a requirement. (AP Photo/TT News Agency, Jonas Ekstromer)

The world is aging so fast that most countries are not prepared to support their swelling numbers of elderly people, according to a global study going out Tuesday by the United Nations and an elder rights group.

30 sept 2013--The report ranks the social and economic well-being of elders in 91 countries, with Sweden coming out on top and Afghanistan at the bottom. It reflects what advocates for the old have been warning, with increasing urgency, for years: Nations are simply not working quickly enough to cope with a population graying faster than ever before. By the year 2050, for the first time in history, seniors over the age of 60 will outnumber children under the age of 15.

Truong Tien Thao, who runs a small tea shop on the sidewalk near his home in Hanoi, Vietnam, is 65 and acutely aware that he, like millions of others, is plunging into old age without a safety net. He wishes he could retire, but he and his 61-year-old wife depend on the $50 a month they earn from the tea shop. And so every day, Thao rises early to open the stall at 6 a.m. and works until 2 p.m., when his wife takes over until closing.

"People at my age should have a rest, but I still have to work to make our ends meet," he says, while waiting for customers at the shop, which sells green tea, cigarettes and chewing gum. "My wife and I have no pension, no health insurance. I'm scared of thinking of being sick—I don't know how I can pay for the medical care."

Thao's story reflects a key point in the report, which was released early to The Associated Press: Aging is an issue across the world. Perhaps surprisingly, the report shows that the fastest aging countries are developing ones, such as Jordan, Laos, Mongolia, Nicaragua and Vietnam, where the number of older people will more than triple by 2050. All ranked in the bottom half of the index.

The Global AgeWatch Index (www.globalagewatch.org) was created by elder advocacy group HelpAge International and the U.N. Population Fund in part to address a lack of international data on the extent and impact of global aging. The index, released on the U.N.'s International Day of Older Persons, compiles data from the U.N., World Health Organization, World Bank and other global agencies, and analyzes income, health, education, employment and age-friendly environment in each country.

The index was welcomed by elder rights advocates, who have long complained that a lack of data has thwarted their attempts to raise the issue on government agendas.

"Unless you measure something, it doesn't really exist in the minds of decision-makers," said John Beard, Director of Ageing and Life Course for the World Health Organization. "One of the challenges for population aging is that we don't even collect the data, let alone start to analyze it. ... For example, we've been talking about how people are living longer, but I can't tell you people are living longer and sicker, or longer in good health."

The report fits into an increasingly complex picture of aging and what it means to the world. On the one hand, the fact that people are living longer is a testament to advances in health careand nutrition, and advocates emphasize that the elderly should be seen not as a burden but as a resource. On the other, many countries still lack a basic social protection floor that provides income, health care and housing for their senior citizens.

In this Sunday, Sept. 29, 2013 photo, an elderly man listens to a speaker at a political rally in New Delhi. Much of the world is not prepared to support the ballooning population of elderly people, including many of the fastest-aging countries, according to a global study scheduled to be released Tuesday, Oct. 1, by the United Nations and an elder rights group. (AP Photo/Altaf Qadri)

Afghanistan, for example, offers no pension to those not in the government. Life expectancy is 59 years for men and 61 for women, compared to a global average of 68 for men and 72 for women, according to U.N. data.

That leaves Abdul Wasay struggling to survive. At 75, the former cook and blacksmith spends most of his day trying to sell toothbrushes and toothpaste on a busy street corner in Kabul's main market. The job nets him just $6 a day—barely enough to support his wife. He can only afford to buy meat twice a month; the family relies mainly on potatoes and curried vegetables.

"It's difficult because my knees are weak and I can't really stand for a long time," he says. "But what can I do? It's even harder in winter, but I can't afford treatment."

Although government hospitals are free, Wasay complains that they provide little treatment and hardly any medicine. He wants to stop working in three years, but is not sure his children can support him. He says many older people cannot find work because they are not strong enough to do day labor, and some resort to begging.

"You have to keep working no matter how old you are—no one is rich enough to stop," he says. "Life is very difficult."

Many governments have resisted tackling the issue partly because it is viewed as hugely complicated, negative and costly—which is not necessarily true, says Silvia Stefanoni, chief executive of HelpAge International. Japan and Germany, she says, have among the highest proportions of elders in the world, but also boast steady economies.

"There's no evidence that an aging population is a population that is economically damaged," she says.

Prosperity in itself does not guarantee protection for the old. The world's rising economic powers—the so-called BRICS nations of Brazil, Russia, India, China and South Africa—rank lower in the index than some poorer countries such as Uruguay and Panama.

In this Thursday, Sept, 26, 2013 photo, Abdul Wasay, 75, sells toothbrushes and toothpaste on a busy street market In Kabul, Afghanistan, where he says he usually spends most of his days. In a country with no pension system for people not in government service, it's a hard life for the former blacksmith and cook. He makes just $6 a day and it's barely enough to help support his wife. (AP Photo/Ahmad Jamshid)

However, the report found, wealthy nations are in general better prepared for aging than poorer ones. Sweden, where the pension system is now 100 years old, makes the top of the list because of its social support, education and health coverage, followed by Norway, Germany, the Netherlands and Canada. The United States comes in eighth.

Sweden's health system earns praise from Marianne Blomberg, an 80-year-old Stockholm resident.

"The health care system, for me, has worked extraordinarily well," she says. "I suffer from atrial fibrillation and from the minute I call emergency until I am discharged, it is absolutely amazing. I can't complain about anything—even the food is good."

Still, even in an elder-friendly country like Sweden, aging is not without its challenges. The Swedish government has suggested people continue working beyond 65, a prospect Blomberg cautiously welcomes but warns should not be a requirement. Blomberg also criticized the nation's finance minister, Anders Borg, for cutting taxes sharply for working Swedes but only marginally for retirees.

"I go to lectures and museums and the theater and those kinds of things, but I probably have to stop that soon because it gets terribly expensive," she says. "If you want to be active like me, it is hard. But to sit home and stare at the walls doesn't cost anything."

© 2013 The Associated Press. All rights reserved.

Link between antidepressants and diabetes risk is real

Clinicians should be extra vigilant when prescribing antidepressants as they could pose a risk of type 2 diabetes, researchers at the University of Southampton have warned.

29 sept 2013--A systematic review, carried out by the University, showed that people taking antidepressants are at a higher risk of type 2 diabetes; however it is not certain whether the medication is responsible.

The use of antidepressant medication has risen sharply over recent years reaching 46.7 million prescriptions issued in the UK in 2011.

A number of studies have been carried out to establish whether antidepressants are linked with diabetes but results have varied depending on the methods used, type of medication and the number of participants.

University of Southampton researchers assessed 22 studies and three previous systematic reviews that looked into the effects of antidepressants on diabetes risk. Overall, people taking antidepressants were more likely to have diabetes. However, the researchers warned that different types of antidepressants may carry different risks and long-term prospective randomized control trials are needed to look at the effects of individual tablets.

Published in Diabetes Care, the team said that there are "several plausible" reasons why antidepressants are associated with an increased risk of diabetes. For example, several antidepressants are associated with significant weight gain which increases the risk of type 2 diabetes. However, they also say that several studies which explored this association still observed an increased risk of diabetes after adjustment for changes in body weight, implying other factors could be involved.

Dr Katharine Barnard, Health Psychologist from the University of Southampton comments: "Antidepressants are used widely in the UK, with a significant increase in their use recently. Our research shows that when you take away all the classic risk factors of type 2 diabetes; weight gain, lifestyle etc, there is something about antidepressants that appears to be an independent risk factor. With 46 million prescriptions a year, this potential increased risk is worrying. Heightened alertness to the possibility of diabetes in people taking antidepressants is necessary until further research is conducted."

Richard Holt, Professor in Diabetes and Endocrinology at the University of Southampton, adds: "While depression is an important clinical problem and antidepressants are effective treatments for this debilitating condition, clinicians need to be aware of the potential risk of diabetes, particularly when using antidepressants in higher doses or for longer duration. When prescribing antidepressants, doctors should be aware of this risk and take steps to monitor for diabetes and reduce that risk of diabetes through lifestyle modification."

More information: Antidepressant Medication as a Risk Factor for Type 2 Diabetes and Impaired Glucose Regulation: Systematic Review, Diabetes Care, 2013.

Provided by University of Southampton