Health

Sitting down all day ‘may accelerate DNA ageing’

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“Women who lead a sedentary lifestyle have faster-ageing cells than those who exercise every day,” BBC News reports.

This research looked at telomeres – often likened to the caps at the end of shoelaces, they are made up of molecules that protect strands of chromosomes from “fraying”.

Telomeres shorten every time the genetic information in cells is duplicated. It’s believed that this leads to cell ageing and death.

In a sample of older women, the researchers looked at whether there was an association between time spent sitting down and telomere length.

Telomeres are measured in the small sections of nucleic acids that make up DNA, known as base pairs.

Among women in the study who did less than about 40 minutes of physical activity a day, those who sat longest had shorter telomeres by an average 170 base pairs.

The researchers say telomeres shorten at a rate of 21 base pairs a year – using a rough “back of a fag packet” calculation, 170 equals about eight years.

Sitting time did not seem linked to telomere length for women who did at least 30 minutes of physical activity a day.

We don’t know whether the results apply to men or younger people.

And, importantly, as the study only looked at the women’s activity levels and telomeres at one point in time, we don’t know whether activity levels or sitting causes telomeres to shorten.

Still, arguably, most of us would benefit from spending less time sitting down.

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Where did the story come from?

The study was carried out by researchers from the University of California, San Diego State University, the State University of New York at Buffalo, the University of Washington, the Fred Hutchinson Cancer Research Centre, George Washington University, the University of Florida and Northwestern University, all in the US.

It was funded by the US National Heart, Lung and Blood Institute.

The study was published in the peer-reviewed American Journal of Epidemiology on an open access basis, so it’s free to read online.

All of the UK media outlets that covered the study implied that a direct cause and effect relationship between sitting down and cell ageing had been proven.

For example, the Mail’s headline stated that, “Women who spend at least 10 hours on their backsides each day speed up their aging process.”

This is untrue. While there certainly seems to be an association worthy of further research, no causal link has been established.

What kind of research was this?

This cross-sectional study used data from women taking part in a much bigger study of health called the Women’s Health Initiative.

Cross-sectional studies can find correlations between different factors – in this case, sitting time and telomere length.

But because this type of study only looks at one point in time, researchers can’t say which factor happened first, so it’s not very useful for telling us whether one causes the other.

What did the research involve?

Researchers used information about 1,481 women aged over 65 who’d taken part in various sub-studies of the Women’s Health Initiative.

They used information from women who’d had their physical activity measured using accelerometers (devices that measure movement) and had also given DNA samples that had been tested for telomere length.

After accounting for other factors, they looked at whether telomere length was linked to the amount of time spent sitting.

The information about physical activity was measured over one week, during which time women wore their accelerometer all the time, except when bathing or swimming.

Women taking part also completed a questionnaire about their physical activity and kept a record of their sleep. Telomere length was measured from DNA in blood cells.

The researchers took account of the following possible confounding factors:

  • age and ethnic background
  • education level
  • marital status
  • smoking and alcohol consumption
  • body mass index
  • hours of moderate to vigorous physical activity each day
  • long-term diseases
  • use of hormone medicines

They also redid their calculations to divide the women into those who did more or less than the average amount of physical activity (about 40 minutes).

They then looked at the link between time spent sitting and telomere length for women who did more or less than 40 minutes physical activity a day.

They also looked at the link between sitting and telomere length for women who did 30 minutes or more a day, the recommended activity level for all adults.

It’s unclear whether these additional calculations were planned from the start of the study, or whether the researchers decided to do them because the initial findings did not show a link between time spent sitting and telomere length.

What were the basic results?

The length of time spent sitting was not linked to telomere length for women who did 30 minutes or more of moderate physical exercise a day.

For women who did less than the average amount of moderate physical activity each day, time spent sitting did show a link to telomere length.

Among these women, those who spent more than about 10 hours a day sitting had shorter telomeres than those who spent less than about eight hours a day sitting. The average difference was 170 base pairs (95% confidence interval [CI] 4 to 340).

Women who spent the most time sitting were more likely to be older, white, obese and have long-term illnesses.

How did the researchers interpret the results?

The researchers said their results suggest that, “Prolonged sedentary time and limited engagement in moderate to vigorous physical activity may act synergistically to shorten leukocyte telomere length among older women.”

In other words, being both sedentary for long periods and not getting much physical activity may act together to shorten telomeres in blood cells.

They speculated that causes of the link might include insulin resistance, lack of the anti-inflammatory responses the body has to exercise, or obesity.

They also acknowledged women who have long-term illnesses are more likely to have a sedentary lifestyle, and the illness rather than the lack of exercise may cause shortened telomeres.

Conclusion

It’s not news to anyone that being more physically active and spending less time sitting around is likely to keep people in better health.

But this study has many limitations that make it difficult for us to rely on its results.

While they are used as a marker for ageing cells, telomeres are not a direct measure of ageing. Although shortened telomeres have been linked to certain diseases, everyone’s telomeres shorten over time.

Saying shorter telomeres make someone “biologically older” doesn’t mean much. This hasn’t stopped the emergence of private companies offering to measure your telomeres – but it’s unclear what exactly you could usefully do with that information.

And the only cells studied in this research were blood cells, so we don’t know whether the results would have held for brain cells, muscle cells or any other cells in the body.

Doctors have tried to disentangle the effects of physical activity from the effects of being sedentary before without much success.

Generally, as in this study, research seems to show that if you get plenty of moderate to vigorous physical exercise, the amount of time you spend sitting or lying down doesn’t make much difference.

The researchers carried out a lot of comparisons and used multiple models to try to show sedentary time was linked to telomere length.

In most of these models, once you take account of women’s age, ethnicity, body mass index and long-term illnesses, there was no link.

Only when the researchers stratified the results by how much physical activity women did could they show a link in one category: those who did the least physical activity.

That suggests sedentary behaviour is not the strongest factor to affect telomere length.

Another problem with the study is it only looked at telomere length and physical activity at one point in the women’s lives.

We don’t know how much physical activity they’d done throughout their lives, or whether their telomeres had shortened faster than other women recently or at an earlier stage in life.

The study doesn’t add much to what we already know: physical activity is likely to be beneficial for people at all stages of life, and everyone should aim to get at least the recommended level of 30 minutes of moderate to vigorous physical activity a day.

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Schizophrenia could be linked to increased risk of type 2 diabetes

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People with schizophrenia are at an increased risk of developing diabetes, even when the effects of antipsychotic drugs, diet and exercise are adjusted for, a new study has found.

Schizophrenia is known to be associated with a reduced life expectancy of up to 30 years. This is largely due to physical health disorders such as heart attack or stroke, for which type 2 diabetes is a major risk factor.

People with long-term schizophrenia are three times more likely than the general population to have diabetes, something which has previously been attributed to poor diet and exercise habits in this group, as well as the use of antipsychotic medication.

Researchers from King’s College London examined whether diabetes risk is already present in people at the onset of schizophrenia, before antipsychotics have been prescribed and before a prolonged period of illness that may be associated with poor lifestyle habits – such as poor diet and sedentary behaviour.

They pooled data from 16 studies comprising 731 patients with a first episode of schizophrenia and 614 people from the general population.

They analysed blood tests from these studies and found that patients with schizophrenia showed higher risk of developing type 2 diabetes compared with healthy controls.

Patients had higher levels of fasting blood glucose, which is a clinical indicator of diabetes risk.

 

Researchers also discovered that compared with healthy controls, patients with first episode schizophrenia had higher levels of insulin and increased levels of insulin resistance, again supporting the notion that this group are at higher risk of developing diabetes.

These results remained significant even when analyses were restricted to studies where patients and controls were matched for dietary intake, the amount of regular exercise they engaged in, and ethnic background.

This suggests that the results were not wholly driven by differences in lifestyle factors or ethnicity between the two groups, and may therefore point towards schizophrenia’s direct role in increasing risk of diabetes.

The researchers highlight several factors that could increase the likelihood of developing both conditions, including shared genetic risk and evidence of shared developmental risk factors, such as premature birth and low birth-weight.

It is also thought that the stress associated with developing schizophrenia, which sees levels of the stress hormone cortisol rise, may also contribute to a higher risk of diabetes.

“Our study highlights the importance of considering physical health at the onset of schizophrenia, and calls for a more holistic approach to its management, combining physical and mental healthcare,” said Toby Pillinger from King’s College London.

The study was published in journal JAMA Psychiatry.

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Depression Immune System / Vaccines Mental Health Clinical Trials / Drug Trials Depression could be treated with anti-inflammatory drugs

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Study leader Dr. Golam Khandaker, of the Department of Psychiatry at the University of Cambridge in the United Kingdom, and colleagues publish their results in the journal Molecular Psychiatry.

Inflammation is the result of the immune system’s response to injury or infection, whereby immune cells release pro-inflammatory proteins – such as cytokines – to help fight harmful pathogens.

But this inflammatory response is not always helpful. Sometimes, the immune system mistakingly launches an attack on healthy cells and tissues, causing autoimmune diseases such as Crohn’s disease, rheumatoid arthritis, and psoriasis.

Increasingly, researchers have suggested that the immune system and inflammation may also play a role in mental health. In 2014, for example, a study from Dr. Khandaker and team found that children with higher levels of cytokines and other “inflammatory markers” were at greater risk of depression and psychosis in later life.

In clinical trials, two new classes of anti-inflammatory drugs – anti-cytokine monoclonal antibodies and cytokine inhibitors – have been shown to reduce inflammation in a range of autoimmune diseases, and these drugs have already started to be administered to patients who do not respond to standard treatments.

Given the potential link between inflammation and depression, Dr. Khandaker and colleagues set out to investigate whether these drugs might also help alleviate symptoms of depression.

Anti-cytokines reduced depression symptoms in clinical trials

For their study, the researchers conducted a meta-analysis of 20 clinical trials that assessed the effects of anti-cytokine monoclonal antibodies and cytokine inhibitors in more than 5,000 patients with autoimmune diseases.

On investigating the additional benefits of the anti-cytokine medications in each trial – seven of which were randomized controlled trials involving a placebo – the team found that the drugs led to a significant reduction in symptoms of depression among participants, regardless of whether they were effective against autoimmune diseases.

While further studies are required, the researchers say their results suggest anti-cytokine medications may be a feasible treatment option for patients with depression – particularly for those who do not respond to current antidepressants.

“About a third of patients who are resistant to antidepressants show evidence of inflammation,” notes Dr. Khandaker. “So, anti-inflammatory treatments could be relevant for a large number of people who suffer from depression.”

“The current approach of a ‘one-size-fits-all’ medicine to treat depression is problematic. All currently available antidepressants target a particular type of neurotransmitter, but a third of patients do not respond to these drugs.

We are now entering the era of ‘personalized medicine’ where we can tailor treatments to individual patients. This approach is starting to show success in treating cancers, and it’s possible that in future we would use anti-inflammatory drugs in psychiatry for certain patients with depression.”

Dr. Golam Khandaker

Still, the team stresses there is still a long way to go before anti-cytokine medications will be used for depression in clinical practice.

“We will need clinical trials to test how effective they are in patients who do not have the chronic conditions for which the drugs have been developed, such as rheumatoid arthritis or Crohn’s disease,” says study co-author Prof. Peter Jones, of the Department of Psychiatry at Cambridge.

“On top of this, some existing drugs can have potentially serious side effects, which would need to be addressed,” he adds.

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Fighting diabetes through yoga, AYUSH activities focus in 2017

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If 2015 saw a marketing blitzkrieg to showcase yoga to the world, this year was about dedicating it and other AYUSH practices for treatment of diabetes. Quality concern in herbal medicine, however, remains a challenge that needs to be addressed through validation and proper enforcement of regulation. Faced with questions about scientific basis of traditional medicines, the AYUSH Ministry entered into an agreement for improving international acceptability and branding of AYUSH systems.

Benchmarks for training in yoga and practice in ayurveda, unani medicine and panchakarma will help ensure the highest standards in quality, safety and effectiveness of traditional medicines, the ministry said. India also partnered with the US to initiate research efforts on traditional medicines for cancer treatment and the first US-India workshop on traditional medicine was held.

Recently, yoga as an “ancient Indian practice” was inscribed on UNESCO’s representative list of Intangible Cultural Heritage of Humanity. On International Yoga Day celebrations in Chandigarh, Prime Minister Narendra Modi appealed to all that yoga must be devoted to fighting diabetes.

“All people belonging to the field of yoga must continue with their yoga activities but diabetes must be the main focus,” he said. Following which a yoga protocol to fight diabetes mellitus, developed by a committee of experts, was unveiled in October. This protocol includes various exercises and diet regimen that a patient can follow.

Continuing with the theme, a national protocol was also launched for treating diabetes through ayurveda. These guidelines prescribe medicines for different symptoms. The protocol also includes a list of fruits and vegetables a diabetic patient should or should not eat. It also recommends an active lifestyle, physical exercise, yoga in order to avoid falling prey to diabetes.

The emphasis on diabetes also landed the ministry in a major controversy after a misleading advertisement of an ayurvedic medicine, AYUSH-82, for diabetes gave a false notion that diabetics could avoid using insulin after taking the drug for a few months.

This was in contravention of Drugs and Magic Remedies Objectionable Advertisements Act-1954 which disallows advertisements of cure for chronic illnesses like diabetes. The advertisement was subsequently pulled off air in October. Questions have also been raised about research and clinical trial methods for AYUSH-82 before making tall claims.

AYUSH Minister Shripad Yesso Naik admitted that quality concern with traditional medicines was a huge challenge. “Many questions are raised about the scientific basis of traditional medicine, their quality, safety and efficacy. It is true that the facet of the traditional and complex herbal formulation can’t be explained fully on the conventional parameters used for testing of chemical drugs.

“But for the sake of safety and consumers to use these medicines with confidence, it is necessary to ensure quality of products,” he said.

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USFDA gives 21 grants for research on RARE DISEASES

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The U.S. Food and Drug Administration today announced that it has awarded 21 new clinical trial research grants totaling more than $23 million over the next four years to boost the development of products for patients with rare diseases. These new grants were awarded to principal investigators from academia and industry with research spanning domestic and international clinical sites.

“We are proud of our 30-year track record of fostering and encouraging the development of safe and effective therapies for rare diseases through our clinical trials grant program,” said Gayatri R. Rao, M.D., J.D., director of FDA’s Office of Orphan Product Development, within the Office of Special Medical Programs. “The grants awarded this year will support much-needed research in 21 different rare diseases, many of which have little, or no, available treatment options.”

The FDA awards the grants through the Orphan Products Clinical Trials Grants Program to encourage clinical development of drugs, biologics, medical devices, or medical foods for use in rare diseases. The grants are intended for clinical studies evaluating the safety and effectiveness of products that could either result in, or substantially contribute to, the FDA approval of products.

Since its creation in 1983, the Orphan Products Clinical Trials Grants Program has provided more than $370 million to fund more than 590 new clinical studies and supported the marketing approval of more than 55 products. Five of the studies funded by this grants program supported product approvals in 2015 alone, including much needed treatments for neuroblastoma, lymphangioleiomyomatosis, hypoparathyroidism, and hypophosphatasia.

Consistent with the tenor set by Vice President Joe Biden’s National Cancer Moonshot Initiative to accelerate cancer research, 24 percent of the new grant awards fund studies enrolling patients with cancer; 40 percent of these studies target devastating forms of brain cancer, one of which recruits children with recurrent or progressive malignant brain tumors.

Forty-three percent of this year’s awards fund studies that enroll pediatric patients as young as newborns. Of these, two focus on research in transplantation and related issues.

In addition, one funded project is a medical device trial to develop a fully implantable neuroprosthesis for grasp, reach, and trunk function in individuals with spinal cord injury with the potential to enable these patients to use their hand, arm, and trunk more independently.

A total of 68 grant applications were received for this fiscal year, with a funding rate of 31 percent (21/68). The grant recipients for fiscal year 2016 include:

Drugs/Biologics:

  • Chemigen, LLC (Zionsville, Indiana), Yansheng Du, Phase 1 Study of CC100 for the Treatment of Amyotrophic Lateral Sclerosis — about $243,000 for one year
  • Chemocentryx, Inc. (Mountain View, California), Petrus Bekker, Phase 2 Study of CCX168 for the Treatment of Anti-Neutrophil Cytoplasmic Auto-Antibodies Associated Vasculitis — $500,000 for one year
  • Columbia University Health Sciences (New York, New York), Elizabeth Shane, Phase 2B Study of Denosumab to Prevent Bone Loss in Idiopathic Osteoporosis in Premenopausal Women Treated with Terripatide — about $1.6 million over four years
  • DNATRIX, Inc. (Houston, Texas), Frank Tufaro, Phase 2 Study of DNX-2401 for the Treatment of Glioblastoma — $2 million over four years
  • Elorac, Inc. (Vernon Hills, Illinois), Scott Phillips, Phase 3 Study of Naloxone Lotion for the Treatment of Pruritus in Mycosis Fungoides — about $2 million over four years
  • Johns Hopkins University (Baltimore, Maryland), Pamela Zeitlin, Phase 1/2 Study of Glycerol Phenylbutyrate for the Treatment of Cystic Fibrosis — $750,000 over three years
  • Oncoceutics, Inc. (Hummelstown, Pennsylvania), Wolfgang Oster, Phase 1/2 Study of ONC201 for the Treatment of Multiple Myeloma — about $1.7 million over four years
  • Oregon Health and Science University (Portland, Oregon), Kevin Winthrop, Phase 2 Study of Clofazimine for the Treatment of Pulmonary Mycobacterium Avium Disease — about $1.8 million over four years
  • Santhera Pharmaceuticals (Liestal, Switzerland), Thomas Meier, Phase 1 Study of Omigapil for the Treatment of Congenital Muscular Dystrophy — $246,000 for one year
  • Scioderm, Inc. (Durham, North Carolina), Jay Barth, Phase 3 Study of SD101 for the Treatment of Epidermolysis Bullosa — $500,000 for one year
  • Seattle Children’s Research Institute (Seattle, Washington), Leslie Kean, Phase 2 Study of Abatacept Combined with Calcineurin Inhibition and Methotrexate for Prophylaxis of Graft Vs Host Disease — $99,630 for one year
  • Sloan-Kettering Institute Cancer Research (New York, New York), Katharine Hsu, Phase 1 Study of Humanized 3F8 MoAb and NK cells for the Treatment of Neuroblastoma — about $750,000 over three years
  • Taimed Biologics USA Corp (Irvine, California), Stanley Lewis, Phase 3 Study of Ibalizumab for the Treatment of Patients with Multidrug Resistant HIV — $500,000 for one year
  • University of Alabama (Birmingham, Alabama), Gregory Friedman, Phase 1 Study of HSV G207 & Radiation for the Treatment of Pediatric Brain Tumors — about $750,000 over three years
  • University of California, San Diego (La Jolla, California), Donald Durden, Phase 1 Study of PI-3 Kinase/BRD4 Inhibitor SF1126 for the Treatment of Hepatocellular Carcinoma — $750,000 over three years
  • University of Florida (Gainesville, Florida), Peter Stacpoole, Phase 3 Study of Dichloroacetate for the Treatment of Pyruvate Dehyrugenase Complex Deficiency — about $2 million over four years
  • University of Michigan (Ann Arbor, Michigan), Kathleen Stringer, Phase 2 Study of Inhaled Activase for the Treatment of Acute Plastic Bronchitis — $2 million over four years
  • University of North Carolina Chapel Hill (Chapel Hill, North Carolina), Matthew Laughon, Phase 2 Study of Furosemide for the Prevention of Bronchopulmonary Dysplasia in Premature Infants — about $1.4 million over four years
  • Vanderbilt University Medical Center (Nashville, Tennessee), Cyndya Shibao, Phase 2 Study of Atomoxetine for the Treatment of Multiple System Atrophy — about $1.6 million over four years
  • Wilson Wolf Manufacturing Corporation (New Brighton, Minnesota), Sunitha Kakarla, Phase 1 Study of Viralym-A for the Treatment of Adenovirus Disease — about $750,000 over three years

Medical Devices:

  • Case Western Reserve University (Cleveland, Ohio), Kevin Kilgore, Phase 2 Study of a Networked Neuroprosthesis for Grasp, Reach, and Trunk Function in Cervical Spinal Cord Injury — about $2 million over four years

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