Study finds new genetic variants associated with extreme old age

The search for the genetic determinants of extreme longevity has been challenging, with the prevalence of centenarians (people older than 100) just one per 5,000 population in developed nations.

29 april 2017--But a recently published study by Boston University School of Public Health and School of Medicine researchers, which combines four studies of extreme longevity, has identified new rare variants in chromosomes 4 and 7 associated with extreme survival and with reduced risks for cardiovascular and Alzheimer's disease.
The results, published in the Journals of Gerontology: Biological Sciences, highlight the importance of studying "truly rare survival, to discover combinations of common and rare variants associated with extreme longevity and longer health span," the authors said.
The research group, led by Paola Sebastiani, professor of biostatistics the BU School of Public Health (BUSPH), created a consortium of four studies—the New England Centenarian Study, the Long Life Family Study, the Southern Italian Centenarian Study, and the Longevity Gene Project - to build a large sample of 2,070 people who survived to the oldest one percentile of survival for the 1900 birth year cohort. The researchers conducted various analyses to discover longevity-associated variants (LAVs), and to characterize those LAVs that differentiated survival to extreme age.
Their analysis identified new "extreme longevity-promoting variants" on chromosomes 4 and 7, while also confirming variants (SNPs, or single nucleotide polymorphisms) previously associated with longevity.
In addition, in two of the datasets where researchers had age-of-onset data for age-related diseases, they found that certain longevity alleles also were significantly associated with reduced risks for cardiovascular disease and hypertension.
"The data and survival analysis provide support for the hypothesis that the genetic makeup of extreme longevity is based on a combination of common and rare variants, with common variants that create the background to survive to relatively common old ages (e.g. into the 80s and 90s), and specific combinations of uncommon and rare variants that add an additional survival advantage to even older ages," the authors wrote.
They said, however, that while the "yield of discovery" in the study was more substantial than in prior genome-wide association studies (GWAS) of extreme longevity, it remained disappointing, in that the two most significant genotypes discovered "are carried by a very small proportion of the cases included in the analysis," meaning that much of the genetic variability around extreme lifespan remains unexplained.
"We expect that many more uncommon genetic variants remain to be discovered through sequencing of centenarian samples," they wrote. "Larger sample sizes are needed to detect association of rare variants... and therefore promising associations that miss the threshold for genome-wide significance are important to discuss."


Provided by Boston University Medical Center

Antidepressant may enhance drug delivery to the brain

Normally, P-glycoprotein prevents most medicines from entering the brain by pumping them back into the blood stream (left). The addition of amitriptyline temporarily turns off P-glycoprotein pumps, allowing drug molecules to cross the blood-brain barrier (right). 

28 april 2017--NIH rat study suggests amitriptyline temporarily inhibits the blood-brain barrier, allowing drugs to enter the brain.
New research from the National Institutes of Health found that pairing the antidepressant amitriptyline with drugs designed to treat central nervous system diseases, enhances drug delivery to the brain by inhibiting the blood-brain barrier in rats. The blood-brain barrier serves as a natural, protective boundary, preventing most drugs from entering the brain. The research, performed in rats, appeared online April 27 in the Journal of Cerebral Blood Flow and Metabolism.
Although researchers caution that more studies are needed to determine whether people will benefit from the discovery, the new finding has the potential to revolutionize treatment for a whole host of brain-centered conditions, including epilepsy, stroke, human amyotrophic lateral sclerosis (ALS), depression, and others. The results are so promising that a provisional patent application has been filed for methods of co-administration of amitriptyline with central nervous system drugs.
According to Ronald Cannon, Ph.D., staff scientist at NIH's National Institute of Environmental Health Sciences (NIEHS), the biggest obstacle to efficiently delivering drugs to the brain is a protein pump called P-glycoprotein. Located along the inner lining of brain blood vessels, P-glycoprotein directs toxins and pharmaceuticals back into the body's circulation before they pass into the brain.
To get an idea of how P-glycoprotein works, Cannon said to think of the protein as a hotel doorman, standing in front of a revolving door at a lobby entrance. A person who is not authorized to enter would get turned away, being ushered back around the revolving door and out into the street.
"For example, as good as vegetables are for us to eat, they have molecules that could be toxic if they slipped into the brain," Cannon said. "They don't get in, because of P-glycoprotein, but this same protector also keeps out helpful therapeutics."
Cannon and his NIEHS colleagues initially found that amitriptyline significantly reduced P-glycoprotein's pump activity in brain capillaries from wild-type rats. Later, they saw amitriptyline had the same effect in brain capillaries from genetically modified rats designed to mimic human ALS. In both rat models, amitriptyline turned off P-glycoprotein within 10-15 minutes. When amitriptyline was removed, P-glycoprotein pump activity returned to full-strength.
NIEHS postbaccalaureate fellow David Banks is lead author on the paper and described amitriptyline's action on P-glycoprotein as rapid and reversible. It's these advantages that make the therapy so appealing.
"Most inventions developed at the bench don't make it to the clinic, but I'm hopeful that our findings will translate into better treatment options for doctors and their patients," Banks said.
Cannon anticipates that administering amitriptyline along with a lower dose of an opioid could relieve pain and reduce the negative side effects, such as constipation and addiction, usually seen with higher doses of prescribed opioids.
"As our nation faces increases in Alzheimer's disease, autism, and opioid abuse, we're hopeful that this discovery will help address these serious health challenges," said NIEHS Director Linda Birnbaum, Ph.D.

More information: David B Banks et al, Lysophosphatidic acid and amitriptyline signal through LPA1R to reduce P-glycoprotein transport at the blood–brain barrier, Journal of Cerebral Blood Flow & Metabolism (2017). DOI: 10.1177/0271678X17705786


Provided by National Institutes of Health

Many patients with Alzheimer's disease discontinue AChEIs

Discontinuation of acetylcholinesterase inhibitors (AChEIs) for treatment of Alzheimer's disease is common, with adverse effects and cost cited as major factors, according to a study published recently in the Journal of the American Geriatrics Society.

27 april 2017--Noll L. Campbell, Pharm.D., from the Purdue University School of Pharmacy in West Lafayette, Ind., and colleagues randomized 196 older adults with a diagnosis of possible or probable Alzheimer's disease who were initiating treatment with an AChEI to one of three AChEIs (1:1:1) for 18 weeks.
In the intent to treat analysis, the researchers found that discontinuation rates at the end of 18 weeks were 38.8 percent for donepezil, 53.0 percent for galantamine, and 58.7 percent for rivastigmine (P = 0.063). Adverse events explained 73.1 percent of discontinuation, while cost explained 25.4 percent. More than 81 percent of participants reported adverse events, but rates were similar between groups.
"This pragmatic comparative trial showed high rates of adverse events and cost-related nonadherence with AChEIs," the authors write.

More information: Abstract
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Suicide and genetics: a complicated association

From Mayo Clinic News Network 

24 april 2017--Dear Mayo Clinic: Why does it seem that suicide tends to run in families? Does it have anything to do with genetics?

A: The association between genetics and suicide is complicated. Research has shown that there is a genetic component to suicide. But it is only one of many factors that may raise an individual's risk. And even if someone is at high risk for suicide, that doesn't predict whether or not an individual will actually act on suicidal thoughts.
Genetic research, including studies involving twins, has revealed that many psychiatric conditions, including having suicidal tendencies, are influenced by genetics. While studies demonstrate that specific genes, such as one called the BDNF Met allele, can increase risk for suicide, it's more likely that a range of genes affect connections and pathways within the brain, and impact suicide risk.
Complicating matters further, a process called epigenetics also comes into play when considering the effect of genes on suicide. This process controls when certain genes are turned on or off as a person grows and develops, and it can be influenced by what happens in a person's environment.
For example, if someone goes through a difficult event as a child, that experience could have an impact on how or when a gene is activated within that person's brain. Researchers speculate that negative experiences influencing epigenetics in a person who has a family history of suicide could further compound that person's suicide risk.
In addition, it is known that 90 percent of people who die by suicide have a psychiatric illness at the time of death. Mood disorders, psychotic disorders, certain personality disorders and substance use disorders can increase suicide risk substantially. Each of those disorders has a genetic component, too.
It's important to understand, however, that an increased risk of suicide does not predict who will commit suicide. For some people - even those whose genetics may seem to predispose them to a higher suicide risk - the thought of suicide doesn't enter their minds. For others, suicide quickly may become a focus of their thoughts.
For those whose thoughts do turn to suicide, the way they arrive at suicidal thoughts may be a well-imprinted and familiar pathway. Psychotherapeutic treatment can help examine the process they go through to get to that point and find ways to interrupt the process.
Genetics, family history and environment all matter when it comes to the risk of suicide. But knowing risk factors is not a substitute for a thorough assessment of an individual's situation and the process he or she takes to arrive at suicidal thoughts.
If you or a loved one are concerned about your risk for suicide, or if you've had suicidal thoughts, talk to a mental health professional. To help you find ways to break the cycle that leads to suicidal thoughts, he or she can work with you to treat any psychiatric illness that may be present and help you understand the process you're going through when you turn to the possibility of suicide.
If you are in a suicide crisis or emotional distress, the National Suicide Prevention Lifeline provides free, confidential emotional support 24/7 at 1-800-273-8255 (toll-free).

Study finds obesity as top cause of preventable life-years lost

A team of researchers from Cleveland Clinic and New York University School of Medicine have found that obesity resulted in as much as 47 percent more life-years lost than tobacco, and tobacco caused similar life-years lost as high blood pressure.

22 april 2017--Preliminary work presented by Cleveland Clinic today at the 2017 Society of General Internal Medicine Annual Meeting analyzed the contribution of modifiable behavioral risk factors to causes-of-death in the U.S. population, using 2014 data.
Based on this preliminary work, the team found the greatest number of preventable life-years lost were due to (in order from greatest to least) obesity, diabetes, tobacco use, high blood pressure and high cholesterol. However, researchers also noted that some individuals may have needs that are very different than those of the broader U.S. population. For an obese and alcoholic patient, for example, alcohol use may be more important to address than obesity, even though obesity has a greater impact on the population.
Results highlight the clinical and public health achievement of smoking cessation efforts because 15 years ago, tobacco would have topped the list.
"Modifiable behavioral risk factors pose a substantial mortality burden in the U.S.," said Glen Taksler, Ph.D., internal medicine researcher from Cleveland Clinic and lead author of the study. "These preliminary results continue to highlight the importance of weight loss, diabetes management and healthy eating in the U.S. population."
A key takeaway is that three (diabetes, hypertension and high cholesterol) of the top five causes of death can be treated, so helping patients understand treatment options and approaches can have a powerful impact on life-years. The results also highlight the importance of preventive care in clinical practice and why it should be a priority for physicians.
To estimate the number of life-years lost to each modifiable risk factor, researchers examined the change in mortality for a series of hypothetical U.S. populations that each eliminated a single risk factor. They compared the results with the change in life-years lost for an "optimal" population that eliminated all modifiable risk factors. Recognizing that some less common factors might place substantial burden on small population subgroups, they also estimated life expectancy gained in individuals with each modifiable risk factor.
"The reality is, while we may know the proximate cause of a patient's death, for example, breast cancer or heart attack, we don't always know the contributing factor(s), such as tobacco use, obesity, alcohol and family history. For each major cause of death, we identified a root cause to understand whether there was a way a person could have lived longer."
Dr. Taksler and colleagues are continuing to conduct research in this area, and analyze and refine results.

More information: Research was presented at The Society of General Internal Medicine 2017 Annual Meeting, "Resilience and Grit: Pursuing Organizational Change & Preventing Burnout in GIM" April 19-22, 2017 in Washington, DC at the Washington Hilton Hotel (1919 Connecticut Avenue, NW Washington, DC 20009).


Provided by Cleveland Clinic

Review finds no benefit to aspirin for preserving cognitive function

An analysis of published studies found no evidence that low- dose aspirin buffers against cognitive decline or dementia or improves cognitive test scores.

21 april 2017--The review and meta-analysis included eight studies with 36,196 participants who were an average of 65 years old and did not have cognitive impairment at baseline. Participants were followed for an average of six years.
"Additional studies are needed to test the possibility that low-dose aspirin has beneficial effects when taken over a longer period and at an earlier age," said Dr. Nicola Veronese, lead author of the Journal of the American Geriatrics Society study.

More information: Nicola Veronese et al, Low-Dose Aspirin Use and Cognitive Function in Older Age: A Systematic Review and Meta-analysis, Journal of the American Geriatrics Society (2017). DOI: 10.1111/jgs.14883

Telestroke guidelines from American Telemedicine Association in Telemedicine and e-Health

Credit: Mary Ann Liebert, Inc., publishers

New guidelines to help clinicians use the latest telemedicine communication technologies to provide remote care for patients with symptoms of acute stroke are published in Telemedicine and e-Health.
Bart Demaerschalk, MD, Mayo Clinic College of Medicine, Phoenix, AZ, and a team of authors contributed to the article entitled "American Telemedicine Association: Telestroke Guidelines."

19 aril 2017-- The guidelines describe the network of audio-visual communication technologies and computer systems available to link an expert stroke team with a stroke physician at a distant site and the clinicians caring for a remote stroke patient, and to deliver telestroke clinical services.
Rapid diagnosis and treatment with a clot-disrupting drug in appropriate patients following ischemic stroke can improve outcomes. The timing of treatment delivery is a critical factor in ischemic stroke.
The coauthors of the new Telestroke Guidelines are from Mayo Clinic College of Medicine (Phoenix), Ascension Health and Columbia College of Nursing (Milwaukee, WI), Medical College of Georgia at Georgia Health Sciences University (Augusta), Yale School of Medicine (New Haven, CT), University of Cincinnati (OH), Massachusetts General Hospital (Boston, MA), University of Pittsburgh (PA), and InTouch Health (Santa Barbara, CA).
"The authors are to be commended for this outstanding work. These guidelines will be of great value to clinicians and the patients they treat," says Charles R. Doarn, MBA, Co-Editor-in-Chief of the Journal and Research Professor of Family and Community Medicine, University of Cincinnati, Ohio.

More information: Bart M. Demaerschalk et al, American Telemedicine Association: Telestroke Guidelines, Telemedicine and e-Health (2017). DOI: 10.1089/tmj.2017.0006


Provided by Mary Ann Liebert, Inc

Major bleeding risk from drugs similar in elderly

The risk of major bleeding is similar for older patients with atrial fibrillation taking either antiplatelet or anticoagulant drugs, according to a review published online April 10 in the Journal of Thrombosis and Haemostasis

18 april 2017--Marc Melkonian, M.D., from the Hôpitaux Universitaires Pitie-Salpêtrière-Charles Foix in France, and colleagues conducted a systematic review and meta-analysis to evaluate major bleeding in randomized and non-randomized controlled trials (RCTs) and parallel cohorts comparing antiplatelet drugs and oral anticoagulants in patients 65 years or older.
Based on seven RCTs (4,550 patients) and four cohort studies (38,649 patients), the researchers found that the risk of major bleeding on aspirin or clopidogrel was equal to that on warfarin in RCTs (relative risk [RR], 1.01; 95 percent confidence interval [CI], 0.69 to 1.48; moderate-quality evidence), lower than on warfarin in non-randomized cohort studies (RR, 0.87; 95 percent CI, 0.77 to 0.99; low-quality evidence), and not different when all studies were combined (RR, 0.86; 95 percent CI, 0.73 to 1.01). Any severity of bleeding (RR, 0.70; 95 percent CI, 0.57 to 0.86) and intracranial bleeding (RR 0.46; 95 percent CI, 0.30 to 0.73) were less frequent on antiplatelet drugs than on warfarin. Major bleeding might be higher with warfarin than aspirin in patients over 80 years old, according to subgroup analysis.
"Elderly patients treated with aspirin or clopidogrel suffer less any-severity bleeding but have a risk of major bleeding similar to that of oral anticoagulants, with the exception of intracranial bleeding," the authors write.

More information: Abstract

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Common sedatives linked to increased risk of pneumonia in people with Alzheimer's disease

Commonly used sedatives called benzodiazepines are associated with an increased risk of pneumonia when used in people with Alzheimer disease, according to a study published in CMAJ (Canadian Medical Association Journal).

17 april 2017--"An increased risk of pneumonia is an important finding to consider in treatment of patients with Alzheimer disease," writes Dr. Heidi Taipale, Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland, with coauthors. "Benzodiazepines and Z-drugs are frequently prescribed for this population, and long-term use is typical. Pneumonia often leads to admission to hospital, and patients with dementia are at increased risk of death related to pneumonia."
Dementia, of which 60%-70% of cases are Alzheimer disease, is a risk factor for pneumonia, and many people with dementia are prescribed benzodiazepines and non- benzodiazepines (called Z-drugs), both of which have sedative effects.
To determine if there is a link between these drugs and pneumonia, Finnish researchers looked at data from national registries on 49 484 adults living in the community diagnosed with Alzheimer disease between 2005 and 2011 in Finland. The mean age of participants was 80 years and almost two-thirds (62.7%) were women. They matched 5232 patients taking benzodiazepines and 3269 patients taking Z-drugs with the remainder not taking either drug.
They found that benzodiazepines were linked to a 30% increased risk of pneumonia in patients with Alzheimer disease, and the risk was highest at the start of treatment (during the first 30 days).
Although the association with Z-drug use and pneumonia was not statistically significant, the authors did not conclude these drugs were safer as the study did not directly compare Z-drugs and benzodiazepines.
The authors suggest that the sedative nature of benzodiazepines may increase the risk of pneumonia by increasing the aspiration of saliva or food into the lungs.
The results are consistent with studies that have found an increased risk of pneumonia in patients of all ages taking benzodiazepines.
"Benefits and risks of the use of benzodiazepines should be carefully considered for patients with Alzheimer disease and include risk of pneumonia," the authors conclude.
In a related commentary, Dr. Paula Rochon from Women's College Hospital and the University of Toronto, with coauthors, writes this study "is a good reminder to clinicians to 'first do no harm' when prescribing these drugs for frail older women and men with dementia. Nonpharmacologic approaches should be the starting point when managing neuropsychiatric symptoms in this patient population, which should help to limit inappropriate use of these drugs."


Provided by Canadian Medical Association Journal

Occupational therapy ups functioning in frail seniors

For physically frail older adults, occupational therapy is associated with improved functioning, according to a review published online April 3 in the Journal of the American Geriatrics Society.

16 april 2017--Leen De Coninck, from the KU Leuven in Belgium, and colleagues conducted a systematic review and meta-analysis to examine the effectiveness of occupational therapy for improving performance in daily living activities among community-dwelling physically frail older people. Data were included from nine studies that met the inclusion criteria.
The researchers found that the studies were of reasonable quality with low risk of bias. Significant increases were seen in all primary outcome measures: mobility, functioning in daily living activities, and social participation. The pooled result was a standardized mean difference of −0.30 for functioning in daily living activities, −0.44 for social participation, and −0.45 for mobility. Positive trends were seen for all secondary outcome measures, with a significant correlation for fear of falling. There were no adverse effects for occupational therapy.
"There is strong evidence that occupational therapy improves functioning in community-dwelling physically frail older people," the authors write.

More information: Abstract

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Italian Emma Morano, last known survivor of 19th century, dies at 117

Emma Morano, then 16, is seen in Verbania, North Italy, on May 14, 2016

Emma Morano, an Italian woman believed to have been the oldest person alive and the last survivor of the 19th century, died Saturday at the age of 117, Italian media reported.
Morano, born on November 29 1899, died at her home in Verbania, in northern Italy, the reports said.
"She had an extraordinary life, and we will always remember her strength to move forward in life," the mayor of Verbania was quoted as saying.

16 april 2017--According to the US-based Gerontology Research Group (GRG), Morano ceded the crown of the world's oldest human being to Jamaican Violet Brown, who was born on March 10, 1900.
Morano's death means there is no one living known to have been born before 1900.
Her first love died in World War I, but she married later and left her violent husband just before the Second World War and shortly after the death in infancy of her only son.
She had clung to her independence, only taking on a full-time carer a couple of years ago, though she had not left her small two-room apartment for 20 years.
She had been bed-bound during her latter years.
In an interview with AFP last year, she put her longevity down to her diet.
"I eat two eggs a day, and that's it. And cookies. But I do not eat much because I have no teeth," she said in her home at the time, where the Guinness World Records certificate declaring her to be the oldest person alive held pride of place on a marble-topped chest of drawers.
Her dietary regime has intrigued the medical and scientific worlds.
The eldest of eight children, Morano outlived all of her younger siblings.

Married LGBT older adults are healthier, happier than singles, study finds

Same-sex marriage has been the law of the land for nearly two years—and in some states for even longer—but researchers can already detect positive health outcomes among couples who have tied the knot, a University of Washington study finds.

14 april 2017--For years, studies have linked marriage with happiness among heterosexual couples. But a study from the UW School of Social Work is among the first to explore the potential benefits of marriage among LGBT couples. It is part of a national, groundbreaking longitudinal study with a representative sample of LGBT older adults, known as "Aging with Pride: National Health, Aging, Sexuality/Gender Study," which focuses on how historical, environmental, psychological, behavioral, social and biological factors are associated with health, aging and quality of life.
UW researchers found that LGBT study participants who were married reported better physical and mental health, more social support and greater financial resources than those who were single. The findings were published in a February special supplement of The Gerontologist.
"In the nearly 50 years since Stonewall, same-sex marriage went from being a pipe dream to a legal quagmire to reality—and it may be one of the most profound changes to social policy in recent history," said lead author Jayn Goldsen, research study supervisor in the UW School of Social Work.
Some 2.7 million adults ages 50 and older identify as lesbian, gay, bisexual or transgender—a number that is expected to nearly double by 2060.
Among LGBT people, marriage increased noticeably after a 2015 U.S. Supreme Court ruling legalized same-sex marriage nationwide. A 2016 Gallup Poll found that 49 percent of cohabiting gay couples were married, up from 38 percent before the ruling.
For the UW study, more than 1,800 LGBT people, ages 50 and older, were surveyed in 2014 in locations where gay marriage was already legal (32 states and Washington, D.C.). About one-fourth were married, another fourth were in a committed relationship, and half were single. Married respondents had spent an average of 23 years together, while those in a committed, unmarried relationship had spent an average of 16 years.
Among the study participants, more women were married than men, and of the respondents who were married, most identified as non-Hispanic white.
Researchers found that, in general, participants in a relationship, whether married or in a long-term partnership, showed better health outcomes than those who were single. But those who were married fared even better, both socially and financially, than couples in unmarried, long-term partnerships.
Single LGBT adults were more likely to have a disability; to report lower physical, psychological, social and environmental quality of life; and to have experienced the death of a partner, especially among men.
The legalization of gay marriage at the federal level opens up access to many benefits, such as tax exemptions and Social Security survivor benefits that married, straight couples have long enjoyed. But that does not mean every LGBT couple was immediately ready to take that step.
According to Goldsen, marriage, for many older LGBT people, can be something of a conundrum—even a non-starter. LGBT seniors came of age at a time when laws and social exclusion kept many in the closet. Today's unmarried couples may have made their own legal arrangements and feel that they don't need the extra step of marriage—or they don't want to participate in a traditionally heterosexual institution.
Goldsen also pointed to trends in heterosexual marriage: Fewer people are getting married, and those who do, do so later.
"More older people are living together and thinking outside the box. This was already happening within the LGBT community—couples were living together, but civil marriage wasn't part of the story," she said.
The different attitudes among older LGBT people toward marriage is something service providers, whether doctors, attorneys or tax professionals, should be aware of, Goldsen said. Telling a couple they should get married now simply because they can misses the individual nature of the choice.
"Service providers need to understand the historical context of this population," she said. "Marriage isn't for everyone. It is up to each person, and there are legal, financial and potentially societal ramifications." For example, among the women in the study, those who were married were more likely to report experiencing bias in the larger community.
At the same time, Goldsen said, single LGBT older adults do not benefit from the marriage ruling, and other safeguards, such as anti-discrimination laws in employment, housing and public accommodations, are still lacking at the federal level.
Over time, Goldsen and colleagues will continue to examine the influence of same-sex marriage policy on partnership status and health.

More information: Jayn Goldsen et al, Who Says I Do: The Changing Context of Marriage and Health and Quality of Life for LGBT Older Adults, The Gerontologist (2017). DOI: 10.1093/geront/gnw174


Provided by University of Washington

Weak grip a strong predictor of metabolic disease and disability in adults

A simple test to determine a person's grip strength may be a predictor of developing metabolic disorders in middle or older age, a new cross-continental study has found. 

A simple test to determine a person's grip strength may be a predictor of developing metabolic disorders in middle or older age, a new cross-continental study has found.
The test locations, demographics and methodology all were selected for a reason.

13 april 2017--"Prevalence of chronic disease is highest in the U.S. and China," says Mark Peterson, Ph.D., M.S., FACSM, assistant professor of physical medicine and rehabilitation at Michigan Medicine and a member of the U-M Global Research, Education and Collaboration in Health and Institute for Healthcare Policy and Innovation. "There's a dire need to identify midlife predictors of disability and diabetes in both populations."
Peterson is the lead author on a new study, published in Journals of Gerontology Series A: Medical Sciences, that investigated if normalized grip strength—which is defined as a person's grip strength divided by their body mass—could serve as a biomarker for both cardiometabolic disease and physical disability in American and Chinese adults.
He teamed up with colleagues from the U-M School of Public Health, Michigan Medicine's Global REACH, the Institute for Social Science Survey and the National School of Development at Peking University in Beijing, China.
One reason for the study's geographic focus: "China represents a unique population," Peterson says. "It's the world's largest population of diabetics, which imposes a huge health and economic burden on their entire country."
He adds, "In 2015, China and the U.S. had a combined $320 billion in diabetes-related health care costs, according to the International Diabetes Federation. The aging populations in both countries are growing because of improved medical care of older adults and longer life expectancy. While on one hand that's great, on the other, it represents two populations that have increasing prevalence estimates of diabetes, cardiovascular health issues and functional impairments. The longer people live with those health issues, the greater the burden is to society."

Analyzing data sets

The research team used data on middle-aged and older adults from the U.S. National Health and Nutrition Examination Survey from 2011 to 2012 and 2013 to 2014, and the 2011 portion of the China Health and Retirement Longitudinal Study. These surveys were selected because they included measures of muscle strength capacity and the necessary information pertaining to disability and cardiometabolic diseases.
"We wanted to examine grip strength in particular because it is highly associated with overall body strength," Peterson says. "To asses someone's grip strength using a handgrip dynamometer takes less than 10 seconds, which makes it extremely attractive to adopt in a clinical or community setting at the population level."
The research team analyzed normalized grip strength for 4,544 U.S. and 6,030 Chinese study participants 50 years of age and older. The study group also had blood samples taken for nonfasting glycated hemoglobin and answered a questionnaire about impairments of functional limitation related to mobility. A subsample of 2,225 adults had fasting measures for glucose, insulin and triglycerides.
Using weighted logistic regression models, the team assessed the association between normalized grip strength and diabetes, hyperglycemia, hypertriglyceridemia, low HDL cholesterol, hypertension and physical disability. They controlled for age, sex and numerous socio-demographic characteristics.

A strong connection

Perhaps the largest finding of the study was that low normalized grip strength was greatly associated with both cardiometabolic diseases and physical disabilities in middle-age to older adults, both men and women, and in both the U.S. and Chinese populations.
For every 0.05 decrement in normalized grip strength in U.S. and Chinese adults, respectively, there were:

• 49 percent and 17 percent increased odds for diabetes
• 46 percent and 11 percent increased odds of hyperglycemia
• 15 percent and 11 percent increased odds of hypertriglyceridemia
• 22 percent and 15 percent increased odds of low HDL cholesterol
• 19 percent and 10 percent increased odds of hypertension
• 36 percent and 11 percent increased odds for disability status

Other highlights from the research team included:

• Prevalence of physical disabilities was higher among older adults (65 years old and older) compared to middle-aged adults (50 years old to 64.9 years old) in both populations.
• In U.S. adults, physical disability status, obesity and abdominal obesity were more prevalent, and diabetes prevalence was higher with increasing age in U.S. men.
• In Chinese adults, diabetes prevalence was higher for women than men in both middle-aged and older adults.
• Diabetes was more prevalent in U.S. than Chinese men in both age categories, but more prevalent in Chinese women than U.S. women.
• Normalized grip strength was higher in Chinese men and women than U.S. men and women in both age categories.

Peterson would like to see these research results translated to the clinical setting.
"We hope these findings illustrate how important a simple grip strength test could be in the clinical setting," Peterson says. "It's an easy way to screen and identify people who are at early risk for these health issues."

More information: Journals of Gerontology Series A: Medical Sciences, DOI: 10.1093/gerona/glx031


Provided by University of Michigan

AGA releases best practice advice on long-term PPI use

When proton pump inhibitors (PPIs) are appropriately prescribed, their benefits are likely to outweigh their risks, according to an American Gastroenterological Association (AGA) Clinical Practice Update1 published in Gastroenterology, the official journal of AGA. Additionally, there is currently insufficient evidence to recommend specific strategies for mitigating PPI adverse effects.

12 april 2017--The long-term use of PPIs by patients for gastroesophageal reflux disease (GERD), Barrett's esophagus and non-steroidal anti-inflammatory drug (NSAID) bleeding prophylaxis doubled in the U.S. from 1999 to 2012. Studies have shown that the number of adverse events doubled during the same period. AGA provides best practice advice for the use of PPIs based on expert opinion and relevant publications:
1. Patients with GERD and acid-related complications should take a PPI for short-term healing, maintenance of healing and long-term symptom control.
2. Patients with uncomplicated GERD who respond to short-term PPIs should subsequently attempt to stop or reduce them. Patients who cannot reduce PPIs should consider ambulatory esophageal pH/impedance monitoring before committing to lifelong PPIs to help distinguish GERD from a functional syndrome.
3. Patients with Barrett's esophagus and symptomatic GERD should take a long-term PPI.
4. Asymptomatic patients with Barrett's esophagus should consider a long-term PPI.
5. Patients at high risk for ulcer-related bleeding from NSAIDs should take a PPI, if they continue to take NSAIDs.
6. The dose of long-term PPIs should be periodically reevaluated so that the lowest effective PPI dose can be prescribed to manage the condition.
7. Long-term PPI users should not routinely use probiotics to prevent infection.
8. Long-term PPI users should not routinely raise their intake of calcium, vitamin B12 or magnesium beyond the recommended dietary allowance.
9. Long-term PPI users should not routinely screen or monitor bone mineral density, serum creatinine, magnesium or vitamin B12.
10. Specific PPI formulations should not be selected based on potential risks.

How to Discuss with Patients

It is necessary for health-care professionals to talk with their patients to ensure high-quality patient care. To help patients understand the importance of using PPIs as directed, AGA has developed talking points for health-care professionals to use to help facilitate discussions about the need to correctly use PPIs for condition and symptom management. Learn more at http://www.gastro.org/patient-care/conditions-diseases/gerd/#Talking to Patients.

1 Freedberg DE, Kim LS, Yang YX, The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association, Gastroenterology (2016), DOI: 10.1053/j.gastro.2017.01.031.

http://www.gastrojournal.org/article/S0016-5085(17)30091-4/fulltext


Provided by American Gastroenterological Association

Mechanism of aging recovery for progeria patients revealed

'Y-27632' drug inhibits the phosphorylation level of ROCK and increases the oxidative phosphorylation efficiency of mitochondria. 

DGIST's research team has identified a mechanism that can recover the aging of patients with Hutchinson-Gilford Progeria Syndrome (HGPS). DGIST announced that the Chair Professor Park SangChul of New Biology (Head of Well-Aging Research Center) and the research team led by Professor Lee YoungSam has discovered a drug that can improve the aging of HGPS patients and identified the mechanism of aging recovery by using the drug.

05 april 2017--HGPS represents one of premature aging syndromes. The patients with HGPS experience growth retardation as well as age-associated symptoms such as skin wrinkles, hair loss, visual impairment, and cardiovascular diseases. Their average life expectancy is 13 years as they age 10 times faster than others. When it comes to aging control, improvement of biological function and solutions for aging of HGPS patients have been big challenges in academia.
This study needs to be highlighted as the research team has identified the molecular causal relationship between ROCK protein activation and mitochondrial dysfunction in the progression of cell senescence for the first time in the world.
DGIST's research team noted that the level of reactive oxygen species increases when mitochondrial function diminishes during the progression fibroblasts of the HGPS patients. By performing high-throughput screening system, the team found 'Y-27632' as an effective agent to control reactive oxygen species and discovered that this drug is effective in improving mitochondrial function.
Mitochondria are intracellular organelles that play a key role in energy and metabolism in cells. It is known that mitochondrial dysfunction causes aging of cells as it increases level of active oxygen and decreases energy production efficiency.
The research team found that 'Y-27632' drug inhibits the phosphorylation level of ROCK and increases the oxidative phosphorylation efficiency of mitochondria. The study also confirms that the drug recovers mitochondrial function and induces the recovery of aging cells by reducing nuclear membrane degeneration and genetic damage that are characteristics of HGPS patient cells.
The Chair Professor Park SangChul stated "This study is significant as we have newly discovered the means to control aging. We have also identified the mechanism to recover the function of aging cell through inhibition and recovery of mitochondrial dysfunction due to aging." He added "We will continue to carry out studies that will extend the healthy lifespan of humans through the verification of the mechanism in aging animal models as well as progeny animal models."

More information: Hyun Tae Kang et al, Chemical screening identifies ROCK as a target for recovering mitochondrial function in Hutchinson-Gilford progeria syndrome, Aging Cell (2017). DOI: 10.1111/acel.12584


Provided by Daegu Gyeongbuk Institute of Science and Technology

Cow's milk interferes with absorption of thyroid supplement levothyroxine

Taking the common oral thyroid hormone medication levothyroxine with a glass of cow's milk significantly decreases the body's ability to absorb the drug, a preliminary study finds. Results will be presented Sunday at ENDO 2017, the Endocrine Society's 99th annual meeting in Orlando, Fla.

02 april 2017--"These findings support previous research showing that calcium supplements can interfere with levothyroxine absorption," said principal investigator Deborah Chon, M.D., an endocrinology fellow at the UCLA David Geffen School of Medicine and the VA (Veterans Affairs) Greater Los Angeles Healthcare System, Los Angeles, Calif. "Decreased absorption means that patients may not get the full dose of thyroid hormone that they are prescribed."
Although it makes sense that milk, which contains calcium, might interfere with levothyroxine absorption, no study has proved that it does until now, according to Chon.
Levothyroxine is prescribed for patients with an underactive thyroid, called hypothyroidism, to replace the natural thyroid hormone thyroxine (T4) that is too low, or for patients with thyroid cancer, to suppress their thyroid stimulating hormone levels. In 2014, levothyroxine was the most commonly prescribed medication in the U.S., a survey from the IMS Institute for Healthcare Informatics (now QuintilesIMS) found.
Chon and fellow investigators studied 10 adults (six men and four women), with an average age of 33.7 years, who had no known thyroid disease and had normal thyroid hormone function at the start of the study. No one was allergic to cow's milk or levothyroxine, and none of the women were pregnant or using birth control pills.
Participants fasted overnight before each of two study visits, spaced a month apart. At one visit, participants took 1,000 micrograms of oral levothyroxine alone and at the other visit, they took the same dose concurrently with 12 ounces of 2 percent milk. Before dosing and one, two, four and six hours after ingestion of levothyroxine, participants gave blood samples for measurement of their total T4 levels. Chon said they tested with generic levothyroxine, which most of their patients are taking.
The investigators measured the levothyroxine absorption as the concentration of total T4 in the blood plotted on a graphic curve against time after drug administration, called area under the curve. Over the six hours after the participants took levothyroxine, those who consumed milk at the same time as the medicine had significantly lower total T4 absorption than when they took the drug alone: average area under the curve of 67.3 versus 73.5.
The manufacturer of a brand of levothyroxine recommends that the medication be taken preferably on an empty stomach, 30 to 60 minutes before eating food or taking other medications or vitamins.
"The main message of this study is that patients managed with thyroid hormone replacement therapy should be advised to avoid taking levothyroxine simultaneously with cow's milk, given its interference," Chon said.


Provided by The Endocrine Society

Brain changes in older adults increase risk for scams

Older adults who have been scammed by friends, relatives or strangers seem to behave just like elders who have avoided rip-offs. They are able to balance their checkbooks. They can remember and evaluate information. Their personalities are normal, and their arithmetic is fine.
But their brains are different.

01 april 2017--For the first time, researchers have found a biological basis for financial exploitation in the elderly. The team is led by a Cornell scientist with collaborators at York University in Toronto.
The exploited older people in their study had more atrophy and less connectivity in two key areas of the brain. One region signals a person when something significant is happening around them, and the other tells them how to read social cues, like other people's intentions. The team published their work March 28 in the Journals of Gerontology.
Together, these age-related changes in the brain may make older adults more vulnerable to financial exploitation – especially when one considers that family members are the most common perpetrators of financial abuse, said the study's lead author, Nathan Spreng, assistant professor of human development and a Rebecca Q. and James C. Morgan Sesquicentennial Faculty Fellow.
"It's not their fault they've been abused. It's not because they made a bad decision. There are biological reasons why these abuses have occurred, and we're trying to get a handle on that," said Spreng, who directs Cornell's Laboratory of Brain and Cognition.
"Older adults are having a harder time navigating these tough social situations. We need to start treating this as a medical problem and not a societal one," he added.
Previous studies have shown that family members are the most common financial abusers. In the study, a grandson continued to steal from a study participant even after she confronted him. A daughter charged $2,000 to a study participant's account without permission. In another instance, a son's girlfriend borrowed $4,000 and never paid it back.
Nearly one in 20 older adults can expect to be financially exploited beyond age 60, an incidence rate that is higher than many age-related diseases like cardiovascular disease, cancer and arthritis.
But this area is not very well studied, Spreng said, because many older adults are unaware or unwilling to report exploitation, embarrassed to reveal they have been scammed or want to protect their privacy. "It's hard to get scientific traction," Spreng said.
He and his colleagues tested 26 older adults, half of whom had been robbed by family members or neighbors or scammed online or by phone. The other half had been exposed to a rip-off scheme but had recognized and avoided it.
The researchers did extensive behavioral tests on both groups to see if they behaved differently. Using 45 assessments, they measured the study participants' memory, ability to pay attention to information and evaluate it, inhibitory control, aspects of personality and financial reasoning.
The only difference in behavior between the two groups was exploited elders reported feeling more anger and hostility.
But more significant differences showed up in the brain images.
The exploited elders had atrophy in the anterior insula and fewer connections from it to a broader brain network. The anterior insula signals when something salient is happening in the environment. In general, this area isn't as responsive in older adults compared with the young, particularly in negative situations, Spreng said.
"If older adults are, say, gambling, they get the same excitement that they might win something as younger adults do, but they don't have the same feeling of dread or disappointment for the losses. So, they're not as sensitive to losing money," he said.
This region was particularly atrophied in the study's exploited group, suggesting that the brain wasn't signaling they were facing a risky situation.
The exploited elders also had more atrophy and fewer neural connections in the medial prefrontal cortex, which helps us appraise social situations, like inferring the thoughts or intentions of others.
Surprisingly, the networks of the anterior insula and the medial prefrontal cortex were more connected to each other. This suggests that poor sensitivity to financial risk combined with reduced detection of untrustworthiness may leave older adults vulnerable to scams.
More, larger studies are needed to validate the neural mechanism, but this study could be a first step in identifying a way to predict who might be vulnerable to financial exploitation, Spreng said.
The time is right, Spreng said, because the current generation of elders is the wealthiest ever.
"There's a huge amount of money locked up in our elders' assets," he said. "And people are actively pursuing them."

More information: R. Nathan Spreng et al. Financial Exploitation Is Associated With Structural and Functional Brain Differences in Healthy Older Adults, The Journals of Gerontology: Series A (2017). DOI: 10.1093/gerona/glx051


Provided by Cornell University

Exercise: the cellular 'fountain of youth'

High-intensity exercise may help older adults reverse certain aspects of the "cellular" aging process, a new study suggests.

30 mar 2017--It's no secret that regular exercise is healthy for young and old alike. But researchers said the new findings point to particular benefits from "high-intensity interval training" for older adults.
That's the type of workout that combines brief bursts of vigorous exercise with periods of moderate activity: A person might, for example, go all-out on a stationary bike for a few minutes, ease up for the next few, and then start again.
In this study, older adults who performed that type of exercise showed greater changes at the cellular level, compared to those who worked out more moderately.
Specifically, interval training gave a bigger boost to mitochondrial function in the muscle. Mitochondria are the "powerhouses" within body cells that break down nutrients to be used for energy.
The training also revved up activity in more genes related to mitochondrial function and muscle growth.
What does it all mean?
The study findings suggest that interval training can turn back the clock in ways that moderate aerobic exercise and strength training do not, according to lead researcher Dr. K. Sreekumaran Nair.
But, he stressed, the findings do not mean older adults should jump into a vigorous exercise regimen.
"If you're sedentary, you should talk to your doctor before you start exercising," said Nair. He's an endocrinologist at the Mayo Clinic in Rochester, Minn.
"And then," he said, "you can start with walking, and build yourself up to a fast pace."
For older adults who want to progress to a more-intense regimen, Nair said, it's best to start with supervision. But he also stressed that intense exercise is not a must. "Any regular exercise will bring health benefits—absolutely," he added.
This study demonstrated that, he pointed out. Even though interval training had the biggest effects on aspects of cellular aging, other types of exercise boosted older adults' fitness levels and muscle strength.
The study, published recently in Cell Metabolism, involved 72 younger and older adults who were sedentary.
Nair's team randomly assigned each of them to one of three supervised exercise groups.
One group did high-intensity interval training three days a week: They pedaled on an exercise bike at their maximum speed for 4 minutes, before easing up for 3 minutes; they repeated that process four times. They also worked out more moderately—walking on a treadmill—twice a week.
A second group performed moderate aerobic exercise—using an exercise bike at a less-intense pace—five days a week, for 30 minutes. They also did some light strength-training four days a week.
The third group performed strengthening exercises only, two days a week.
After 12 weeks, all of the groups were showing positive changes—younger and older exercisers alike, the researchers found.
People who performed moderate aerobic exercise boosted their fitness levels—the body's ability to supply blood and oxygen to working muscles. And the improvement was greater for older adults, who generally started out with lower fitness levels than younger people.
Meanwhile, people who performed strength-training—alone or with aerobic exercise—increased their muscle strength.
The interval-training group showed only small gains in strength. But the training improved mitochondrial function in the muscles, especially among older adults.
Dr. Chip Lavie is medical director of cardiac rehabilitation and prevention at the John Ochsner Heart and Vascular Institute in New Orleans.
He said this is a "great" study that demonstrates the benefits of different forms of exercise.
According to Lavie, it adds to other evidence that high-intensity interval training is "probably the best form of exercise."
Many studies, he said, have found that interval training beats moderate aerobic exercise when it comes to improving fitness and the heart's structure and function.
"It would be ideal to get more people to do high-intensity interval training," Lavie said, "and it's possible for more-motivated individuals."
But, he added, the reality is, many people may not have the motivation or ability.
In that case, Lavie advised finding a moderate regimen you can live with—such as 30 to 40 minutes of walking or using an exercise bike or elliptical machine most days of the week.

More information: K. Sreekumaran Nair, M.D., Ph.D., professor, medicine, Mayo Clinic, Rochester, Minn.; Chip Lavie, M.D., medical director, cardiac rehabilitation and prevention, and director, exercise laboratories, John Ochsner Heart and Vascular Institute, New Orleans; March 7, 2017, Cell Metabolism

The American Council on Exercise has more on interval training.

Elevated blood pressure not a high mortality risk for elderly with weak grip

A study of nearly 7,500 Americans age 65 or older suggests that elevated blood pressure is not related to high mortality risk among people in that age group with weak grip strength.

New research by Oregon State University builds on an earlier OSU study that showed the relationship between high blood pressure and risk of death is largely dependent on elders' frailty status as measured by walking speed.

29 mar 2017--The findings are important because they suggest that treating high blood pressure in older patients should not follow a one-size-fits-all approach. When an older person is still functioning at a high level physically, high blood pressure indicates mortality risk; however, when the person is not physically robust, high blood pressure is not a marker for mortality risk.
"If people are very frail, they typically don't respond well to anti-hypertensive therapy and they are not benefiting from having a low blood pressure," said lead author Chenkai Wu, a graduate student in OSU's College of Public Health and Human Sciences. "The research is basically saying older adults are not one single group, they're very different in terms of their health status, and drugs may not have the same benefits for everyone. This is consistent with the idea of precision medicine, where you don't just look at age, you look at other things like functional status."
Measured in millimeters of mercury, blood pressure is the force of blood against the vessel walls. Systolic blood pressure, the higher number, is the force during a heartbeat, and diastolic refers to when the heart is at rest.
Most people's diastolic blood pressure goes down with age. Systolic blood pressure, though, tends to rise, and high blood pressure - hypertension - can put extra strain on the heart and arteries, causing greater risk of heart attack and stroke.
But as Wu's research suggests, an elderly patient's level of physical functionality should be considered in determining whether anti-hypertensive therapy is warranted.
Grip strength, easily measured by an inexpensive device known as a dynamometer, is a common way to gauge functionality in the elderly. Another often-used measuring stick is walking speed.
Wu looked at data from 7,492 people age 65 or older who had taken part in the nationally representative Health and Retirement Study. Six years after being surveyed, 25 percent of those people had died.
The study showed that elevated systolic blood pressure (150 or greater) and diastolic blood pressure (90 or greater) correlated with a substantially higher likelihood of dying for those with normal grip strength, which is 26 kilograms or more for men and 16 kilograms or more for women.
"We did three analyses," Wu said. "One was to look at gait speed to separate people into two groups, normal and slow. The second part was grip strength - weak grip and normal grip. Third, we looked at the combinations, and the strongest inverse association between high blood pressure and mortality was for slow walkers with weak grip strength.
"Both measures are markers of functional status, a multidimensional concept. Considering both might be better than considering each measure alone for identifying subgroups of elders for whom high blood pressure is potentially beneficial."
OSU public health epidemiologist Michelle Odden, senior author on the study and the lead author on the earlier gait-speed research, explained how high blood pressure might actually help in some cases.
"As we age, our blood vessels lose elasticity and become stiff," said Odden, an assistant professor in the College of Public Health and Human Sciences. "Higher blood pressure could be a compensatory mechanism to overcome this loss of vascular elasticity and keep fresh blood pumping to the brain and heart.
"And everyone ages differently - there is a profound difference between the physiological age of an 80-year-old man who golfs every day and someone who needs a walker to get around. So with fast walkers, high blood pressure may be more indicative of underlying disease and not just a symptom of the aging process."
In addition to the connection with weak grip strength, Wu said there was a "very clear" inverse association between high blood pressure and mortality among those who weren't physically able to finish the gait-speed test in the latest study, measured over a 98.5-inch walk.
Put another way, among those who couldn't walk a little over 8 feet, high blood pressure was associated with less mortality risk.
"It's a small group but not negligible - 6 percent - of people who were not able to complete the test," he said. "Compared to grip strength, it's a harder test to complete, an integration of a lot of physiological systems: balance, vision, lower-extremity muscle strength, etc."
The findings were recently published in the Journal of the American Geriatrics Society.

More information: Chenkai Wu et al, Functional Status Modifies the Association of Blood Pressure with Death in Elders: Health and Retirement Study, Journal of the American Geriatrics Society (2017). DOI: 10.1111/jgs.14816


Provided by Oregon State University

Longer telomeres protect against diseases of aging: A tale of mice and men

Deepak Srivastava, MD, is the Younger Family Director and a Senior Investigator at the Gladstone Institute of Cardiovascular Disease and Director of the Roddenberry Stem Cell Center.

Scientists at the Gladstone Institutes discovered a key mechanism that protects mice from developing a human disease of aging, and begins to explain the wide spectrum of disease severity often seen in humans. Both aspects center on the critical role of telomeres, protective caps on the ends of chromosomes that erode with age.

28 mar 2017--Erosion of telomeres has long been associated with diseases of aging, but how telomere length affects human disease has remained largely a mystery. Now, scientists find that shortening telomeres in mice carrying a human genetic mutation linked to heart disease results in a deadly buildup of calcium in heart valves and vessels. This innovative model allows the researchers to test viable new drugs for this disease, and it provides a potential solution to studying other human disorders of aging in mice.
Calcific aortic valve disease (CAVD) causes calcium to accumulate in heart valves and vessels until they harden like bone. It can only be treated by replacing the valve through heart surgery and is the third leading cause of heart disease, affecting three percent of adults over the age of 75. CAVD develops with age, and it can be caused by a mutation in one of two copies of the NOTCH1 gene.
Humans typically have two copies of each gene. When one copy is lost, the remaining gene may not produce enough of its protein to sustain normal function. While reducing protein levels by half often causes disease in humans, mice with the same change are frequently protected from disease, but scientists have been unsure why. In the new study, published in the Journal of Clinical Investigation, the Gladstone scientists linked telomere length to risk for or resistance to these types of diseases. Laboratory mice have naturally longer telomeres than humans, which the researchers now think protects them from age-related genetic conditions, such as CAVD.
"Our findings reveal a critical role for telomere length in a mouse model of age-dependent human disease," said first author Christina Theodoris, an MD/PhD student in the laboratory of Deepak Srivastava, MD. "This model provides a unique opportunity to dissect the mechanisms by which telomeres affect age-dependent disease and also a system to test novel therapeutics for aortic valve disease."
The researchers, who previously identified NOTCH1 as a genetic culprit in human CAVD, created mice that had shorter telomeres and were also missing one copy of the NOTCH1 gene, since mutation of NOTCH1 alone failed to induce valve disease in mice. Remarkably, mice with both shorter telomeres and the NOTCH1 mutation showed all the cardiac abnormalities seen in humans, including the disease-defining calcification of the aortic valve. Mice with the shortest telomeres had the greatest heart damage, with some even showing signs of valve disease as newborns. The scientists think that telomere length affects disease severity by changing gene expression in pathways implicated in CAVD, such as anti-inflammatory and anti-calcifications pathways.
Previous studies found that patients with valve calcification have shorter telomeres than healthy individuals of the same age. Additionally, some patients who have the NOTCH1 mutation develop CAVD in their 50s, while others are born with deadly valve abnormalities. Based on the new findings, the researchers suspect telomere length explains the variations in disease severity.
"Historically, we have had trouble modeling human diseases caused by mutation of just one copy of a gene in mice, which impedes research on complex conditions and limits our discovery of therapeutics," explained Srivastava, director of the Gladstone Institute of Cardiovascular Disease and senior author on the study. "Progressive shortening of longer telomeres that are protective in mice not only reproduced the clinical disease caused by NOTCH1 mutation, it also recapitulated the spectrum of disease severity we see in humans."
Prior research by Helen Blau, PhD, and Foteini Mourkioti, PhD, of Stanford University—who were co-authors on the current study—demonstrated that shortening telomeres in a mouse model of Duchenne muscular dystrophy also elicited a more human-like disease, raising the possibility that telomere length may be protective for many disease-causing mutations.
The researchers plan to use the mouse models of CAVD to test several potential drug therapies they identified, in the hopes of discovering the first medical treatment for the disease.

More information: Christina V. Theodoris et al. Long telomeres protect against age-dependent cardiac disease caused by NOTCH1 haploinsufficiency, Journal of Clinical Investigation (2017). DOI: 10.1172/JCI90338


Provided by Gladstone Institutes

Exercising 2.5 hours per week associated with slower declines in Parkinson's disease patients

Parkinson's disease (PD) is a progressive condition that often results in mobility impairments and can lead to decreased health-related quality of life (HRQL) and death. There is evidence that physical activity can delay decline in PD patients. In a study in the Journal of Parkinson's Disease, researchers determined that that people who exercised regularly had significantly slower declines in HRQL and mobility over a two-year period.

27 mar 2017--Lead investigator Miriam R. Rafferty, PhD, of Northwestern University and Rehabilitation Institute of Chicago, describes the main findings of the study. "We found that people with Parkinson's disease who maintained exercise 150 minutes per week had a smaller decline in quality of life and mobility over two years compared to people who did not exercise or exercised less. The smaller decline was significant for people who started the study as regular exercisers, as well as for people who started to exercise 150 minutes per week after their first study-related visit."
The data came from the National Parkinson Foundation Quality Improvement Initiative (NPF-QII), an international, multicenter, prospective clinical study of care and outcomes that has recorded data from 21 sites in North America, the Netherlands, and Israel identified as Centers of Excellence by the National Parkinson Foundation. Over 3400 participants provided data over two years, with information collected during at least three clinic visits. The NPF-QII study collects demographics, disease duration, Hoehn and Yahr stage (HY), brief cognitive assessments, as well as data on pharmacologic and non-pharmacologic management of PD symptoms. These observational study visits are scheduled on a yearly basis. At each visit, exercise is measured by the self-reported number of hours per week of exercise.
The Parkinson Disease Questionnaire (PDQ-39) is used to measure patient-reported, PD-specific HRQL. Functional mobility was measured by the Timed Up and Go (TUG) test, in which performance is tested by timing participants as they rise from a chair, walk three meters, turn, and return to a sitting position.
Although this study did not determine which type of exercise is best, it suggests that any type of exercise done with a "dose" of at least 150 minutes per week is better than not exercising. "People with PD should feel empowered to find the type of exercise they enjoy, even those with more advanced symptoms," remarked Dr. Rafferty.
An unanticipated finding from the study was that the HRQL benefit associated with 30-minute increases in exercise per week was greatest in people with advanced PD. These data have significant implications for making exercise and physical activity more accessible to people with more severe disability. People with more advanced PD may have poor access to regular exercise, as their mobility impairments would limit their independent participation in existing community and group exercise programs.
"The most important part of the study," according to Dr. Rafferty, "is that it suggests that people who are not currently achieving recommended levels of exercise could start to exercise today to lessen the declines in quality of life and mobility that can occur with this progressive disease."

More information: Miriam R. Rafferty et al, Regular Exercise, Quality of Life, and Mobility in Parkinson's Disease: A Longitudinal Analysis of National Parkinson Foundation Quality Improvement Initiative Data, Journal of Parkinson's Disease (2017). DOI: 10.3233/JPD-160912


Provided by IOS Press

Hospital or home? Guidelines to assess older people who have fallen

Guidelines to help paramedics make the right decision for older people who have fallen are safe, cost-effective and help reduce further 999 calls, according to new research led by a team at Swansea University Medical School.

26 mar 2017--Falls are a very common problem in older people, with severe consequences. Many 999 calls are made for older people who fall. Many callers fall more than once.

• Approximately 30% of people over 65 living at home fall every year
• In the UK, falls account for almost £1 billion of the NHS budget
• Around 8% of 999 calls in the UK are for falls

If the person who has fallen is not injured they may be left at home by the ambulance crew, rather than taken to hospital. On average this happens in around 40% of cases currently. In some places ambulance services have made local links with community falls services. However, there is not enough evidence to show whether this is safe, effective for patients or worth the cost.
This is where the Swansea research comes in, part of a project called SAFER 2 (Support and Assessment for Fall Emergency Referrals). The team carried out a large-scale trial to test new guidelines - known as a protocol - for paramedics to use to assess people following a 999 call for a fall. The protocol helps them decide whether they should take the patient to hospital, or leave them at home with a referral to a community-based falls service if appropriate
The trial involved105 paramedics based at 14 ambulance stations, across three UK ambulance services. The team monitored over 4000 people who called for an ambulance after falling.
The research showed that the new protocol:

• Was safe and inexpensive
• Led to an 11% decrease in further 999 calls by people who have fallen - so there would now be 8 calls for every 9 made previously
• Left fewer people without continuing care after their fall
• Did not have any wider effects on Accident and Emergency admissions or death rates
• Had limited effects on patients' quality of life or satisfaction
• Was not used as much or as consistently by paramedics as expected

Professor Helen Snooks of Swansea University Medical School, who led the project, said:
"The findings show that this new way of assessing patients who fall is safe. Ambulance services can introduce it knowing that it does not increase the risk of harm to patients.
We also showed that the protocol was associated with a small reduction in 999 calls from patients who had fallen previously. As costs and pressures are so high in emergency care, even a small reduction can make a big difference."


Provided by Swansea University

After the epigenome: The epitranscriptome

Chemical modifications of nucleic acids constitute the Epigenome (DNA) and the Epitranscriptome (RNA), which regulate the activity of the Genome.

Our genome is made up of 6,000 million pieces of DNA that combine four "flavors": A, C, G and T (Adenine, Cytosine, Guanine and Thymine). It is our Alphabet. But to this base we must add some regulation, just like the spelling and grammar of that alphabet: this is what we call Epigenetics.

25 mar 2017--In epigenetics, there there are "accents", called DNA methylation, which means having a C or a methyl-C. The first one usually means that a gene is expressed and active, while the second one implies that a gene is silent and inactive. Our DNA "speaks" when it produces another molecule called RNA (Ribonucleic Acid). Until very recently, it was believed that this molecule was only a poorly regulated intermediate capable of producing proteins (such as insulin, hemoglobin and others) under DNA's orders.
Today, an article published in Cancer Discovery by Manel Esteller, Director of the Epigenetics and Cancer Biology Program of Bellvitge Biomedical Research Institute (IDIBELL), ICREA Researcher and Professor of Genetics at the University of Barcelona, explains that this RNA also has its own spelling and grammar, just like DNA. These "epigenetics of RNA" are called epitranscriptome.
"It is well-known that sometimes DNA produces a RNA string but then this RNA does not originate the protein. Because in these cases the alteration is neither in the genome nor the proteome, we thought it should be in the transcriptome, that is, in the RNA molecule", Dr. Esteller explains."In recent years, we discovered that our RNA is highly regulated and if only two or three modifications at the DNA level can control it, there may be hundreds of small changes in RNA that control its stability, its intracellular localization or its maturation in living beings".
In human cells, this field did not start to be studied in depth in the last five years. "For example, we now know that RNA can be methylated just like DNA and in a highly specific way", says Dr. Manel Esteller, "and even more recently we observed that these epigenetic modifications of RNA may be key in the regulation of "guardian" RNAs, also called non-coding RNAs".
The article also points out that the epitranscriptome could be altered in some human diseases, while alterations in genes responsible for cancer are also being discovered. "It will definitely be an exciting research stage for this and the next generation of scientists," concludes the researcher.

More information: Manel Esteller et al, The Epitranscriptome of Noncoding RNAs in Cancer, Cancer Discovery (2017). DOI: 10.1158/2159-8290.CD-16-1292


Provided by IDIBELL-Bellvitge Biomedical Research Institute

Moderate drinking linked to lower risk of some—but not all—heart conditions

Moderate drinking is associated with a lower risk of several, but not all, cardiovascular diseases, finds a large study of UK adults published by The BMJ today.

The finding that moderate drinking is not universally associated with a lower risk of all cardiovascular conditions suggests a more nuanced approach to the role of alcohol in prevention of cardiovascular disease is necessary, say the researchers.

24 mar 2016--Moderate drinking is thought to be associated with a lower risk of developing cardiovascular disease compared with abstinence or heavy drinking.
In the UK, moderate drinking is defined as no more than 14 units (112 grams) of alcohol a week.
To put this into context, one unit of alcohol is about equal to half a pint of ordinary strength beer, lager or cider (3.6% alcohol by volume) or a small pub measure (25 ml) of spirits. There are one and a half units of alcohol in small glass (125 ml) of ordinary strength wine (12% alcohol by volume). [Source: NHS Choices]
There is, however, a growing scepticism around this observation, with some experts pointing out several shortcomings in the evidence. For example, grouping non-drinkers with former drinkers, who may have stopped drinking due to poor health.
So researchers at the University of Cambridge and University College London set out to investigate the association between alcohol consumption and 12 cardiovascular diseases by analysing electronic health records for 1.93 million healthy UK adults as part of the CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records) data resource.
All participants were free from cardiovascular disease at the start of the study, and non-drinkers were separated from former and occasional drinkers to provide additional clarity in this debate.
After several influential factors were accounted for, moderate drinking was associated with a lower risk of first presenting to a doctor with several, but not all, cardiovascular conditions, including angina, heart failure and ischaemic stroke, compared with abstaining from alcohol.
However, the authors argue that it would be unwise to encourage individuals to take up drinking as a means of lowering their cardiovascular risk over safer and more effective ways, such as increasing physical activity and stopping smoking.
Heavy drinking (exceeding recommended limits) conferred an increased risk of first presenting with a range of such diseases, including heart failure, cardiac arrest and ischaemic stroke compared with moderate drinking, but carried a lower risk of heart attack and angina.
Again, the authors explain that this does not mean that heavy drinkers will not go on to experience a heart attack in the future, just that they were less likely to present with this as their first diagnosis compared with moderate drinkers.
This is an observational study, so no firm conclusions can be drawn about cause and effect. Added to which, the authors point to some study limitations that could have introduced bias.
Nevertheless, they say it is the first time this association has been investigated on such a large scale and their findings have implications for patient counselling, public health communication, and disease prediction tools.
In a linked editorial, researchers at Harvard Medical School and Johns Hopkins School of Public Health in the US say this study "does not offer a materially new view of the associations between alcohol consumed within recommended limits and risk of cardiovascular disease.
"This work, however, sets the stage for ever larger and more sophisticated studies that will attempt to harness the flood of big data into a stream of useful, reliable, and unbiased findings that can inform public health, clinical care, and the direction of future research," they conclude.

More information: Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records, www.bmj.com/content/356/bmj.j909


Provided by British Medical Journal

Shingles vaccine cuts chronic pain, hospitalizations

23 mar 2017--—Vaccination greatly reduces the risk of serious complications from shingles, a new study finds.
Shingles occurs when the same virus that causes chickenpox is reactivated later in life. Nearly one-third of people in the United States will develop shingles. The risk increases with age, researchers said.
The new study showed the vaccine was 74 percent effective in preventing hospitalizations for shingles during the three years after vaccination. That number dropped to 55 percent effective after four or more years.
The immunization was 57 percent effective for preventing lasting pain in the three years after vaccination. The rate dropped to 45 percent after four years, the researchers said.
The findings were published recently in the journal Clinical Infectious Diseases.
"The fact that we found relatively high effectiveness against serious outcomes, such as hospitalization and [lasting pain], and that protection from these outcomes was sustained over time, adds to the considerable evidence that the vaccine is beneficial and that seniors should be encouraged to be vaccinated in higher numbers than what is happening currently," study author Dr. Hector Izurieta said in a journal news release.
Izurieta is with the U.S. Food and Drug Administration's Center for Biologics Evaluation and Research. The FDA funded the research.
The study looked at information collected between 2007 and 2014. The data included about 2 million Medicare beneficiaries. The researchers found that the vaccine seems most effective against severe cases of shingles requiring hospitalization and against chronic pain.
There didn't seem to be much difference in how effective the vaccine was between age groups. But protection declined over time after vaccination, the researchers said.
The shingles vaccine was approved in the United States in 2006. At the time, studies showed that the vaccine reduced the risk of shingles by about half in people aged 60 and older.
In the United States, the shingles vaccine is recommended for people 60 and older. But in 2014, just 28 percent of adults in this age group said they'd received the vaccine, according to the U.S. Centers for Disease Control and Prevention.

More information: The U.S. Centers for Disease Control and Prevention has more on shingles vaccination.

Screening for both malnutrition and frailty needed to enhance health of aging populations

By 2035 one in four Canadians will be 65 years old or older, an age group prone to malnutrition and frailty. A new literature review published today in Applied Physiology, Nutrition, and Metabolism describes the similarities between these two conditions, which are generally considered separately by clinicians, and recommends research efforts, diagnostic tools and medical treatments that consider both conditions.

21 mar 2017--Frailty in older populations is characterized by loss in strength and endurance, which increases vulnerability to other ailments and overall deterioration of health. Frail, older adults struggle with everyday activities such as cooking and eating, putting them at risk for malnourishment. Previous studies have found that malnutrition often co-occurs with frailty in older adults, exacerbating the condition and causing further weakness. Even though the two conditions coincide with each other, currently, frailty and malnutrition are diagnosed independently of each other using different tools. "Simple tools for screening and processes for detecting and treating these conditions together need to be developed across the continuum of care," says Professor Heather Keller, senior author of the review and lead of the University of Waterloo's Nutrition and Aging Lab. Frailty and malnutrition "should be considered simultaneously due to the high likelihood that a patient will have both conditions together," Keller adds.
Keller and her research team compiled documents and reports on frailty and malnutrition and identified symptoms shared between the two conditions: weight loss, slowness and weakness. Weight loss can be self-reported or measured, while the latter two symptoms can be readily assessed in any healthcare setting using reduced walking speed and grip strength of a patient's hand. The authors believe that the use of indicators that diagnose both malnutrition and frailty is needed to ensure that effective treatments are used to improve the health of seniors.
The review stresses how treatment plans that address both malnutrition and frailty are currently lacking and their effectiveness is not known. Oral nutritional supplements or nutrient dense diets in combination with physical exercise could improve nutrition status and strength in frail, malnourished patients.
Preventative health practices that capture both nutrition and frailty risk are also important, the authors say. Identifying at-risk individuals with standardized screening can ensure earlier intervention, which can minimize progression of the conditions and hospitalization. The authors conclude that when a health professional considers an older adult to be frail, they should also identify if they are malnourished.
This review is timely given Canada's shifting demographic. Additional burdens on Canada's healthcare system are expected over the next 20 years as a quarter of the country's population will exceed the age of 65 by 2035. Testing and implementing diagnostic and treatment tools that detect related health conditions such as frailty and malnutrition can improve efficiency of hospital and primary care services, and ultimately patient outcomes.

More information: Applied Physiology, Nutrition, and Metabolism, DOI: 10.1139/apnm-2016-0652


Provided by Canadian Science Publishing (NRC Research Press)