Study shows cyclic breathing technique more effective in reducing stress than mindfulness meditation

At team of researchers at Stanford University reports evidence that people who engage in cyclic sighing breathing exercises see a greater reduction in stress than those engaging in mindfulness meditation. In their paper published in the journal Cell Reports Medicine, the researchers describe their study of several different types of stress reduction techniques.

17 jan 2023--Prior research has shown that while stress can be a positive influence at times, such as when it prompts people to do things they know they need to do, more often, it is considered adverse because it can lead to health problems such as hypertension. Thus, stress techniques have been developed to help people reduce stress without resorting to drugs. One such technique is mindfulness meditation, during which a person attempts to relax by putting themselves in the moment in a nonjudgmental way for a period of time. Other techniques involve engaging in breathing exercises. In this new effort, the researchers compared three types of breathing exercises and mindfulness meditation to assess their effectiveness.

The three types of breathing exercises tested included cyclic sighing, in which more time and thought is spent on exhaling than on inhaling or holding the breath; box breathing, in which breathing and holding are done for the same amount of time; and cyclic hyperventilation, in which inhalations last longer than exhalations.

Research for the study was conducted online during the pandemic when stress was unusually high for most people; 114 volunteers engaged in one of the stress reducers for five minutes each day for a month at the time of their choosing. Each volunteer kept a stress journal to assess the effectiveness of their stress reduction activities.

The researchers found that for the most part, the volunteers reported that they found the exercise a positive experience—90% reported positive feelings. They also found that those volunteers using breathing exercises showed more stress reduction than those doing mindfulness meditation. And they also found that those who did cyclic sighing reported the greatest reductions in stress compared to the other breathing techniques.

More information: Melis Yilmaz Balban et al, Brief structured respiration practices enhance mood and reduce physiological arousal, Cell Reports Medicine (2023). DOI: 10.1016/j.xcrm.2022.100895

 

Loss of epigenetic information can drive aging, restoration can reverse it

An international study 13 years in the making demonstrates for the first time that degradation in the way DNA is organized and regulated—known as epigenetics—can drive aging in an organism, independently of changes to the genetic code itself.

17 jan 2023--The work shows that a breakdown in epigenetic information causes mice to age and that restoring the integrity of the epigenome reverses those signs of aging.

Findings are published online Jan. 12 in Cell.

"We believe ours is the first study to show epigenetic change as a primary driver of aging in mammals," said the paper's senior author, David Sinclair, professor of genetics in the Blavatnik Institute at Harvard Medical School and co-director of the Paul F. Glenn Center for Biology of Aging Research.

The team's extensive series of experiments provide long-awaited confirmation that DNA changes are not the only—or even the main—cause of aging. Rather, the findings show, chemical and structural changes to chromatin—the complex of DNA and proteins that forms chromosomes—fuel aging without altering the genetic code itself.

"We expect the findings will transform the way we view the process of aging and the way we approach the treatment of diseases associated with aging," said co-first author Jae-Hyun Yang, research fellow in genetics in the Sinclair lab.

The authors say that because it's easier to manipulate the molecules that control epigenetic processes than to reverse DNA mutations, the work points to new avenues that focus on epigenetics rather than genetics to prevent or treat age-related damage.

First, the results need to be replicated in larger mammals and in humans. Studies in nonhuman primates are currently underway.

"We hope these results are seen as a turning point in our ability to control aging," said Sinclair. "This is the first study showing that we can have precise control of the biological age of a complex animal; that we can drive it forwards and backwards at will."

Beyond mutations

Perhaps the most burning question for those who study aging is what causes it.

For decades, a reigning theory in the field was that aging arises from an accumulation of changes to DNA, primarily genetic mutations, which over time prevent more and more genes from functioning properly. These malfunctions, in turn, cause cells to lose their identity, so that tissues and organs break down, leading to disease and ultimately death.

In recent years, however, studies have increasingly hinted that there's more to the story.

For instance, some researchers found that some people and mice with high mutation rates don't show signs of premature aging. Others observed that many types of aged cells have few or no mutations.

Researchers started wondering what else works with or instead of DNA changes to cause aging. A list of possible culprits grew. Among them were epigenetic changes.

A component of epigenetics is the physical structures such as histones that bundle DNA into tightly compacted chromatin and unspool portions of that DNA when needed. Genes are inaccessible when they're bundled up but available to be copied and used to produce proteins when they're unspooled. Thus, epigenetic factors regulate which genes are active or inactive in any given cell at any given time.

By acting as a toggle for gene activity, these epigenetic molecules help define cell type and function. Since each cell in an organism has basically the same DNA, it's the on-off switching of particular genes that differentiates a nerve cell from a muscle cell from a lung cell.

"Epigenetics is like a cell's operating system, telling it how to use the same genetic material differently," said Yang, who is co-first author with Motoshi Hayano, a former postdoctoral fellow in the Sinclair lab who is now at Keio University School of Medicine in Tokyo.

In the late 1990s and early 2000s, Sinclair's lab and others showed in yeast and mammals that epigenetic changes accompany aging. Yet they couldn't tell whether these changes drove aging or were a consequence of it.

It wasn't until the current study that Sinclair's team was able to disentangle epigenetic from genetic changes and confirm that a breakdown in epigenetic information does, in fact, contribute to aging in mice.

ICE mice

The team's main experiment involved creating temporary, fast-healing cuts in the DNA of lab mice.

These breaks mimicked the low-grade, ongoing breaks in chromosomes that mammalian cells experience every day in response to things like breathing, exposure to sunlight and cosmic rays, and contact with certain chemicals.

In the study, to test whether aging results from this process, the researchers sped the number of breaks to simulate life on fast-forward.

The team also ensured that most of the breaks were not made within the coding regions of the mice's DNA—the segments that make up genes. This prevented the animals' genes from developing mutations. Instead, the breaks altered the way DNA is folded.

Sinclair and colleagues called their system ICE, short for inducible changes to the epigenome.

At first, epigenetic factors paused their normal job of regulating genes and moved to the DNA breaks to coordinate repairs. Afterward, the factors returned to their original locations.

But as time passed, things changed. The researchers noticed that these factors got "distracted" and did not return home after repairing breaks. The epigenome grew disorganized and began to lose its original information. Chromatin got condensed and unspooled in the wrong patterns, a hallmark of epigenetic malfunction.

As the mice lost their youthful epigenetic function, they began to look and act old. The researchers saw a rise in biomarkers that indicate aging. Cells lost their identities as, for example, muscle or skin cells. Tissue function faltered. Organs failed.

The team used a recent tool developed by Sinclair's lab to measure how old the mice were, not chronologically, in days or months, but "biologically," based on how many sites across the genome lost the methyl groups normally attached to them. Compared to untreated mice born at the same time, the ICE mice had aged significantly more.

Young again

Next, the researchers gave the mice a gene therapy that reversed the epigenetic changes they'd caused.

"It's like rebooting a malfunctioning computer," said Sinclair.

The therapy delivered a trio of genes—Oct4, Sox2, and Klf4, together named OSK—that are active in stem cells and can help rewind mature cells to an earlier state. (Sinclair's lab used this cocktail to restore sight in blind mice in 2020.)

The ICE mice's organs and tissues resumed a youthful state.

The therapy "set in motion an epigenetic program that led cells to restore the epigenetic information they had when they were young," said Sinclair. "It's a permanent reset."

How exactly OSK treatment achieved that remains unclear.

At this stage, Sinclair says the discovery supports the hypothesis that mammalian cells maintain a kind of backup copy of epigenetic software, that when accessed, can allow an aged, epigenetically scrambled cell to reboot into a youthful, healthy state.

For now, the extensive experiments led the team to conclude that "by manipulating the epigenome, aging can be driven forwards and backwards," said Yang.

From here

The ICE method offers researchers a new way to explore the role of epigenetics in aging and other biological processes.

Because signs of aging developed in the ICE mice after only six months rather than toward the end of the average mouse life span of two and a half years, the approach also saves time and money for researchers studying aging.

Researchers can also look beyond OSK gene therapy in exploring how lost epigenetic information might be restored in aged organisms.

"There are other ways to manipulate the epigenome, like drugs and small molecule chemicals that induce gentle stress," said Yang. "This work opens a door for applying those other methods to rejuvenate cells and tissues."

Sinclair hopes the work inspires other scientists to study how to control aging to prevent and eliminate age-related diseases and conditions in humans, such as cardiovascular disease, type 2 diabetes, neurodegeneration, and frailty.

"These are all manifestations of aging that we've been trying to treat with medicines when they arise, which is almost too late," he said.

The goal would be to address the root causes of aging to extend human health span: the number of years that a person remains not just alive but well.

Medical applications are a long way off and will take extensive experiments in multiple cell and animal models. But, Sinclair said, scientists should think big and keep trying in order to achieve such dreams.

"We're talking about taking someone who's old or sick and making their whole body or a specific organ young again, so the disease goes away," he said. "It's a big idea. It's not how we typically do medicine."

More information: Jae-Hyun Yang et al, Loss of epigenetic information as a cause of mammalian aging, Cell (2023). DOI: 10.1016/j.cell.2022.12.027

 

A prescription for prolonged sitting: A five-minute stroll every half hour

Mounting evidence suggests that prolonged sitting—a staple of modern-day life—is hazardous to your health, even if you exercise regularly. Based on these findings, doctors advise all adults to sit less and move more.

17 jan 2023--But how often do we need to get up from our chairs? And for how long?

Few studies have compared multiple options to come up with the answer most office workers want: What is the least amount of activity needed to counteract the health impact of a workday filled with sitting?

Now a study by Columbia University exercise physiologists has an answer: just five minutes of walking every half hour during periods of prolonged sitting can offset some of the most harmful effects.

The study, led by Keith Diaz, Ph.D., associate professor of behavioral medicine at Columbia University Vagelos College of Physicians and Surgeons, was published online in Medicine & Science in Sports & Exercise, the journal of the American College of Sports Medicine.

Unlike other studies that test one or two activity options, Diaz's study tested five different exercise "snacks": one minute of walking after every 30 minutes of sitting, one minute after 60 minutes; five minutes every 30; five minutes every 60; and no walking.

"If we hadn't compared multiple options and varied the frequency and duration of the exercise, we would have only been able to provide people with our best guesses of the optimal routine," Diaz says.

Each of the 11 adults who participated in the study came to Diaz's laboratory, where participants sat in an ergonomic chair for eight hours, rising only for their prescribed exercise snack of treadmill walking or a bathroom break. Researchers kept an eye on each participant to ensure they did not over- or under-exercise and periodically measured the participants' blood pressure and blood sugar (key indicators of cardiovascular health). Participants were allowed to work on a laptop, read, and use their phones during the sessions and were provided standardized meals.

The optimal amount of movement, the researchers found, was five minutes of walking every 30 minutes. This was the only amount that significantly lowered both blood sugar and blood pressure. In addition, this walking regimen had a dramatic effect on how the participants responded to large meals, reducing blood sugar spikes by 58% compared with sitting all day.

Taking a walking break every 30 minutes for one minute also provided modest benefits for blood sugar levels throughout the day, while walking every 60 minutes (either for one minute or five minutes) provided no benefit.

All amounts of walking significantly reduced blood pressure by 4 to 5 mmHg compared with sitting all day. "This is a sizeable decrease, comparable to the reduction you would expect from exercising daily for six months," says Diaz.

The researchers also periodically measured participants' levels of mood, fatigue, and cognitive performance during the testing. All walking regimens, except walking one minute every hour, led to significant decreases in fatigue and significant improvements in mood. None of the walking regimens influenced cognition.

"The effects on mood and fatigue are important," Diaz says. "People tend to repeat behaviors that make them feel good and that are enjoyable."

The Columbia researchers are currently testing 25 different doses of walking on health outcomes and testing a wider variety of people: Participants in the current study were in their 40s, 50s, and 60s, and most did not have diabetes or high blood pressure.

"What we know now is that for optimal health, you need to move regularly at work, in addition to a daily exercise routine," says Diaz. "While that may sound impractical, our findings show that even small amounts of walking spread through the work day can significantly lower your risk of heart disease and other chronic illnesses."

The study is titled "Breaking Up Prolonged Sitting to Improve Cardiometabolic Risk: Dose-Response Analysis of a Randomized Cross-Over Trial."

The other contributors are Andrea T. Duran (Columbia), Ciaran P. Friel (Feinstein Institutes of Medical Research, Northwell Health), Maria A. Serafini (Columbia), Ipek Ensari (Columbia), and Ying Kuen Cheung (Columbia).

More information: Breaking Up Prolonged Sitting to Improve Cardiometabolic Risk: Dose-Response Analysis of a Randomized Cross-Over Trial, Medicine & Science in Sports & Exercise (2023).

 

Eating almonds daily boosts exercise recovery molecule by 69% among 'weekend warriors'

For those who exercise regularly, eating almonds each day might be the ideal new year's resolution. A randomized controlled trial in Frontiers in Nutrition showed that female and male participants who ate 57g almonds daily for one month had more of the beneficial fat 12,13-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME) in their blood immediately after a session of intense exercise than control participants. This molecule, a so-called oxylipin (oxidized fat) is synthetized from linoleic acid by brown fat tissue, and has a beneficial effect on metabolic health and energy regulation.

17 jan 2023--Corresponding author Dr. David C Nieman, a professor and director of the Appalachian State University Human Performance Laboratory at the North Carolina Research Campus, said, "Here we show that volunteers who consumed 57g of almonds daily for one month before a single 'weekend warrior' exercise bout had more beneficial 12,13-DiHOME in their blood immediately after exercising than control volunteers. They also reported feeling less fatigue and tension, better leg-back strength, and decreased muscle damage after exercise than control volunteers."

Four week dietary supplementation with almonds

The clinical trial involved 38 men and 26 women between the ages of 30 and 65, who didn't engage in regular weight training. Approximately half were randomized to the almond diet group, and the other half to the control group, who daily ate a calorie-matched cereal bar. The researchers took blood and urine samples before and after the four-week period of dietary supplementation. Performance measures included a 30 second Wingate anaerobic test, a 50 meter shuttle run test, and vertical jump, bench press, and leg-back strength exercises. Additional blood and urine samples were taken immediately after this 90 minute session of 'eccentric exercise' and daily for four days afterwards.

After each blood draw, the participants filled out the 'Profile of Mood States' (POMS) questionnaire to quantify their mental state, and rated their delayed onset muscle soreness—that is, pain and stiffness felt after unaccustomed or strenuous exercise—on a 10-interval scale.

As expected, the 90 minute exercise led to an increase in the volunteers' self-reported feeling of muscle damage and muscle soreness, as well as an increased POMS score, indicating self-reported decreased vigor and increased fatigue, anxiety, and depression.

The exercise also resulted in transient elevated levels of pro-inflammatory cytokines such as IL-6, IL-8, IL-10, and MCP-1 in the blood, consistent with minor muscle damage. However, these changes in cytokines were equal in the almond and cereal bar groups.

Differences in two DiHOME concentrations

Importantly, immediately after exercise, the concentration of the beneficial 12,13-DiHOME was 69% higher in blood plasma of participants in the almond group than in participants in the control group. 12,13-DiHOME is known to increase the transport of fatty acid and its uptake by skeletal muscle, with the overall effect of stimulating metabolic recovery after exercise.

The reverse pattern was found for another oxylipin, the mildly toxic 9,10-Dihydroxy-12-octadecenoic acid (9,10-diHOME), which was 40% higher immediately after exercise in the blood of the control group than in the almond group. Unlike 12,13-DiHOME, 9,10-diHOME has been shown have negative effects on overall health and the body's recovery to exercise.

Polyphenols in almond skin may be key

Nieman and colleagues concluded that daily consumption of almonds leads to a change in metabolism, downregulating inflammation and oxidative stress from exercise and enabling the body to recover faster.

"We conclude that almonds provide a unique and complex nutrient and polyphenol mixture that may support metabolic recovery from stressful levels of exercise. Almonds have high amounts of protein, healthy types of fats, vitamin E, minerals, and fiber. And the brown skin of almonds contains polyphenols that end up in the large intestine and help control inflammation and oxidative stress," said Nieman.

More information: "Almond intake alters the acute plasma dihydroxy-octadecenoic acid (DiHOME) response to eccentric exercise, Frontiers in Nutrition (2023). DOI: 10.3389/fnut.2022.1042719

 

ACP recommends bisphosphonates for initial treatment for osteoporosis in males and postmenopausal females

The American College of Physicians (ACP) has issued an update of its guideline with clinical recommendations for treatments of primary osteoporosis and low bone mass in adults. In the new guideline, ACP recommends bisphosphonates as initial pharmacologic treatment to reduce the risk of fractures in males and postmenopausal females diagnosed with primary osteoporosis. The full guideline is published in Annals of Internal Medicine.

17 jan 2023--Osteoporosis is a systemic skeletal disease characterized by decreasing bone mass and deterioration of bone tissue that leads to an increased risk for bone fragility and fracture, especially in the hip, spine, and wrist. Overall, an estimated 10.2 million people aged 50 and older in the United States have osteoporosis and about 43.3 million people (> 40% of older US adults) have low bone mass associated with a high risk of progression to osteoporosis.

The guideline examines new evidence that has emerged on the efficacy of human parathyroid hormone-related peptides, sclerostin inhibitors, the comparative effectiveness of treatments, and treatments in males. In postmenopausal females and males with primary osteoporosis, bisphosphonates had the most favorable balance between benefits, harms, patient values and preferences, and cost among the drug classes that were evaluated. In addition to net clinical benefits, bisphosphonates are much cheaper than other pharmacologic treatments and are available in generic oral and injectable formulations.

Current evidence suggests that increasing the duration of bisphosphonate therapy longer than 3-5 years reduced the risk of new vertebral fractures but not the risk of other fractures. However, there is an increased risk of long-term harms. Therefore, clinicians should consider stopping bisphosphonates after five years of treatment unless there is a strong indication to continue treatment.

The guideline also suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in postmenopausal females and males diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates.

ACP suggests that clinicians use the sclerostin inhibitor (romosozumab) or recombinant PTH (teriparatide), followed by a bisphosphonate, to reduce the risk of fractures only in females with primary osteoporosis with very high risk of fracture.

The guideline is based on a systemic review and network meta-analysis conducted by the ACP Center for Evidence Reviews at the Portland Veteran Affairs Research Foundation. ACP's Clinical Guidelines Committee is planning to maintain this topic as a living guideline with literature surveillance and periodic updating of the systematic review and the clinical recommendations.

More information: Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians, Annals of Internal Medicine (2023). DOI: 10.7326/M22-1034

Chelsea Ayers et al, Effectiveness and Safety of Treatments to Prevent Fractures in People With Low Bone Mass or Primary Osteoporosis, Annals of Internal Medicine (2023). DOI: 10.7326/M22-0684

Susan M. Ott, Osteoporosis Treatment: Not Easy, Annals of Internal Medicine (2023). DOI: 10.7326/M22-3580

 

Good hydration linked to healthy aging

Adults who stay well-hydrated appear to be healthier, develop fewer chronic conditions, such as heart and lung disease, and live longer than those who may not get sufficient fluids, according to a National Institutes of Health study published in eBioMedicine.     Using health data gathered from 11,255 adults over a 30-year period, researchers analyzed links between serum sodium levels—which go up when fluid intake goes down—and various indicators of health. They found that adults with serum sodium levels at the higher end of a normal range were more likely to develop chronic conditions and show signs of advanced biological aging than those with serum sodium levels in the medium ranges. Adults with higher levels were also more likely to die at a younger age. 

17 jan 2023--"The results suggest that proper hydration may slow down aging and prolong a disease-free life," said Natalia Dmitrieva, Ph.D., a study author and researcher in the Laboratory of Cardiovascular Regenerative Medicine at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH.  

The study expands on research the scientists published in March 2022, which found links between higher ranges of normal serum sodium levels and increased risks for heart failure. Both findings came from the Atherosclerosis Risk in Communities (ARIC) study, which includes sub-studies involving thousands of Black and white adults from throughout the United States. The first ARIC sub-study started in 1987 and has helped researchers better understand risk factors for heart disease, while shaping clinical guidelines for its treatment and prevention. 

  For this latest analysis, researchers assessed information study participants shared during five medical visits—the first two when they were in their 50s, and the last when they were between ages 70-90. To allow for a fair comparison between how hydration correlated with health outcomes, researchers excluded adults who had high levels of serum sodium at baseline check-ins or with underlying conditions, like obesity, that could affect serum sodium levels.   They then evaluated how serum sodium levels correlated with biological aging, which was assessed through 15 health markers. This included factors, such as systolic blood pressure, cholesterol, and blood sugar, which provided insight about how well each person's cardiovascular, respiratory, metabolic, renal, and immune system was functioning. They also adjusted for factors, like age, race, biological sex, smoking status, and hypertension.

They found that adults with higher levels of normal serum sodium—with normal ranges falling between 135-146 milliequivalents per liter (mEq/L)—were more likely to show signs of faster biological aging. This was based on indictors like metabolic and cardiovascular health, lung function, and inflammation. For example, adults with serum sodium levels above 142 mEq/L had a 10-15% associated increased odds of being biologically older than their chronological age compared to ranges between 137-142 mEq/L, while levels above 144 mEq/L correlated with a 50% increase. Likewise, levels of 144.5-146 mEq/L were associated with a 21% increased risk of premature death compared to ranges between 137-142 mEq/L.  Similarly, adults with serum sodium levels above 142 mEq/L had up to a 64% increased associated risk for developing chronic diseases like heart failure, stroke, atrial fibrillation and peripheral artery disease, as well as chronic lung disease, diabetes, and dementia. Conversely, adults with serum sodium levels between 138-140 mEq/L had the lowest risk of developing chronic disease.   The findings don't prove a causal effect, the researchers noted. Randomized, controlled trials are necessary to determine if optimal hydration can promote healthy aging, prevent disease, and lead to a longer life. However, the associations can still inform clinical practice and guide personal health behavior.  

"People whose serum sodium is 142 mEq/L or higher would benefit from evaluation of their fluid intake," Dmitrieva said. She noted that most people can safely increase their fluid intake to meet recommended levels, which can be done with water as well as other fluids, like juices, or vegetables and fruits with a high water content. The National Academies of Medicine, for example, suggest that most women consume around 6-9 cups (1.5-2.2 liters) of fluids daily and for men, 8-12 cups (2-3 liters). 

Others may need medical guidance due to underlying health conditions. "The goal is to ensure patients are taking in enough fluids, while assessing factors, like medications, that may lead to fluid loss," said Manfred Boehm, M.D., a study author and director of the Laboratory of Cardiovascular Regenerative Medicine. "Doctors may also need to defer to a patient's current treatment plan, such as limiting fluid intake for heart failure." The authors also cited research that finds about half of people worldwide don't meet recommendations for daily total water intake, which often starts at 6 cups (1.5 liters).  

"On the global level, this can have a big impact," Dmitrieva said. "Decreased body water content is the most common factor that increases serum sodium, which is why the results suggest that staying well hydrated may slow down the aging process and prevent or delay chronic disease."      This research was supported by the Division of Intramural Research at NHLBI. The ARIC study has been supported by research contracts from NHLBI, NIH, and the Department of Health and Human Services.          

More information: Natalia I. Dmitrieva et al, Middle-age high normal serum sodium as a risk factor for accelerated biological aging, chronic diseases, and premature mortality, eBioMedicine (2023). DOI: 10.1016/j.ebiom.2022.104404

 

Stranded dolphins' brains show common signs of Alzheimer's disease

The brains of three species of stranded dolphins show classic markers of human Alzheimer's disease, according to the most extensive study into dementia in odontocetes (toothed whales).

17 jan 2023--The new pan-Scotland research, a collaboration between the University of Glasgow, the Universities of St Andrews and Edinburgh and the Moredun Research Institute, studied the brains of 22 odontocetes which had all been stranded in Scottish coastal waters.

The study, which is published in the European Journal of Neuroscience, included five different species—Risso's dolphins, long-finned pilot whales, white-beaked dolphins, harbor porpoises and bottlenose dolphins—and found that four animals from different dolphin species had some of the brain changes associated with Alzheimer's disease in humans.

The findings may provide a possible answer to unexplained live-stranding events in some odontocete species. Study authors confirm the results could support the "sick-leader" theory, whereby an otherwise healthy pod of animals find themselves in dangerously shallow waters after following a group leader who may have become confused or lost.

Whales, dolphins and porpoises are regularly stranded around the coasts of the U.K. They are often found stranded in groups, or pods, in shallow waters and sometimes on beaches. While some animals can be moved to safer, deeper waters by teams of experts, other animals are less lucky and perish as a result. The underlying causes of live stranding events are not always clear, and research is ongoing to gain better insights.

For this study researchers examined stranded animals for the presence of the brain pathology that are part of the hallmarks of Alzheimer's disease, including the formation of amyloid-beta plaques, the accumulation of phospho-tau and gliosis (a change in cell numbers in response to central nervous system damage). The results reveal that the brains of all of the aged animals studied had amyloid-beta plaques.

Three animals in particular—each from a different odontocete species—had amyloid-beta plaques as well as a number of other dementia-related pathologies in their brains, showing that some odontocete species develop Alzheimer's-like neuropathology. However, the study cannot confirm whether any of the animals would have suffered with the same cognitive deficits associated with clinical Alzheimer's disease in humans.

Lead researcher, Dr. Mark Dagleish from the University of Glasgow, said, "These are significant findings that show, for the first time, that the brain pathology in stranded odontocetes is similar to the brains of humans affected by clinical Alzheimer's disease.

"While it is tempting at this stage to speculate that the presence of these brain lesions in odontocetes indicates that they may also suffer with the cognitive deficits associated with human Alzheimer's disease, more research must be done to better understand what is happening to these animals."

Co-author, Professor Frank Gunn-Moore from the University of St Andrews, said, "I have always been interested in answering the question: do only humans get dementia? Our findings answer this question as it shows potential dementia associated pathology is indeed not just seen in human patients. This study is also a great example of both different research institutes, but also different branches of the Life Sciences working together."

Professor Tara Spires-Jones, University of Edinburgh, said, "We were fascinated to see brain changes in aged dolphins similar to those in human aging and Alzheimer's disease. Whether these pathological changes contribute to these animals stranding is an interesting and important question for future work."

All animals in this research were studied after a stranding event. Marine Scotland and Defra fund post-mortem examinations, via the Scottish Marine Animal Stranding Scheme (SMASS), of cetaceans (including odontocetes), pinnipeds and marine turtles that strand and die in Scottish coastal waters.

The paper, "Alzheimer's disease-like neuropathology in three species of oceanic dolphin," is published in the European Journal of Neuroscience.

More information: Marissa C. Vacher et al, Alzheimer's disease‐like neuropathology in three species of oceanic dolphin, European Journal of Neuroscience (2022). DOI: 10.1111/ejn.15900

 

Exercise and diet reaffirmed as key to healthy aging

While many people are aware humans typically lose strength and mobility as they age, fewer realize this is not inevitable and can largely be prevented by diet and appropriate exercise.

17 jan 2023--Geriatrician and current Ph.D. researcher Dr. Jesse Zanker from the University of Melbourne says this age-related loss of strength and mobility is known as sarcopenia in which, from about the age of 30, muscles begin losing their youthful bulk.

"In older age this can have serious impacts on a person's ability to remain independent and engage in meaningful activities," he says.

"With targeted action, however, loss of muscle and its negative outcomes can be delayed, prevented and even reversed."

Co-researcher Victoria University's Professor Alan Hayes from the Institute for Health and Sport said "there are many reasons that people can lose muscle, such as inactivity and hospitalization, which exacerbates losses seen with aging. Muscles can respond at any age, but waiting until there are difficulties with simple activities of daily living is too late."

While establishing clear guidelines for diagnosing sarcopenia are important, it was pleasing to see that clinicians, researchers and consumers agreed that exercise and diet are the cornerstone of healthy aging.

But knowledge of Sarcopenia remains low among both public and health professionals alike.

There are numerous causes of sarcopenia, with age being the most common. Inflammation as we age, is thought to play a key role. Illness, such as COVID-19 or influenza infection, can also speed up muscle loss.

So what can we do about it?

Dr. Zanker, at the 2020 the annual meeting of the Australian and New Zealand Society for Sarcopenia and Frailty Research, recognized that sarcopenia knowledge and action remain poor.

Over two years, they sought opinions from people living with sarcopenia and their caregivers ("consumer experts"), and clinicians and researchers ("topic experts"), to develop comprehensive guidelines for sarcopenia prevention and management in Australia and New Zealand. These guidelines were published in the Journal of Cachexia, Sarcopenia and Muscle in November 2022.

"Experts unanimously agreed with the evidence that the key approach to sarcopenia is simple—exercise and diet. Despite progress in medical research and the particular focus of drug companies targeting chronic diseases of older age, a prescription of exercise remains the gold standard," Dr. Zanker says.

"But not just any exercise. While walking is the most common form of exercise and is good for our physical, emotional and social health, walking on its own doesn't reduce our risk of falls or reverse sarcopenia. The key to sarcopenia treatment is known as progressive resistance training (PRT), which involves a gradual, repeated, and targeted increase in weight or 'resistance' over time."

A healthy diet includes adequate protein and calorie intake; the building blocks and fuel to optimize the effects of PRT. With the support of a doctor and allied health professionals (such as exercise physiologists, physiotherapists and dietitians), publicly funded exercise and diet plans can be developed that match consumer preferences.

Dr. Zanker reports that in their study, consumer experts shared different opinions from topic experts on their preferred duration of an exercise consultation, where they'd like to undertake exercise, and what outcomes were most important them.

For example, the mental health impacts of sarcopenia were reported to be of greater concern than reduced ability to perform household tasks. This led topic experts to reflect on why sarcopenia remains largely unknown in the public sphere. The answer being that until now experts haven't been seeking the input of people living with it.

Dr. Zanker recommends anyone concerned about sarcopenia should speak with their health provider and get moving.

"It is never too late to start making positive changes and never too early to begin," he says.

More information: Jesse Zanker et al, Consensus guidelines for sarcopenia prevention, diagnosis and management in Australia and New Zealand, Journal of Cachexia, Sarcopenia and Muscle (2022). DOI: 10.1002/jcsm.13115

 

The potential benefit of metformin to reduce delirium risk and mortality

A new research paper titled "The potential benefit of metformin to reduce delirium risk and mortality: a retrospective cohort study" has been published in Aging.

17 jan 2023--Metformin has been reported to improve age-related disorders, including dementia, and to lower mortality. This study was conducted to investigate whether metformin use lowers delirium risk, as well as long-term mortality.

In the current retrospective cohort study, researchers from Stanford University School of Medicine, University of Iowa Carver College of Medicine, University of Iowa College of Public Health, and Tottori University Faculty of Medicine analyzed 1,404 previously recruited subjects. The relationship between metformin use and delirium, and the relationship between metformin use and 3-year mortality were investigated.

The researchers state, "Thus, in this report we aimed to investigate the relationship between DM [diabetes mellitus] and delirium risk with a focus on the influence from metformin. We hypothesized that history of metformin use is associated with lower risk for delirium. We were also interested in testing if history of metformin use can alter one of the most important patient outcomes, mortality."

In total, 242 subjects were categorized into a type 2 diabetes mellitus (DM)-without-metformin group, and 264 subjects were categorized into a DM-with-metformin group. Prevalence of delirium was 36.0% in the DM-without-metformin group, and 29.2% in the DM-with-metformin group. A history of metformin use reduced the risk of delirium in patients with DM (OR, 0.50 [95% CI, 0.32 to 0.79]) after controlling for confounding factors.

The 3-year mortality in the DM-without-metformin group (survival rate, 0.595 [95% CI, 0.512 to 0.669]) was higher than in the DM-with-metformin group (survival rate, 0.695 [95% CI, 0.604 to 0.770]) (p=0.035). A history of metformin use decreased the risk of 3-year mortality after adjustment for confounding factors (HR, 0.69 [95% CI, 0.48 to 0.98]). The researchers concluded that metformin use may lower the risk of delirium and mortality in DM patients.

"In this report, we showed the potential benefit of metformin in decreasing the risk of delirium and mortality in DM subjects," the researchers conclude.

More information: Takehiko Yamanashi et al, The potential benefit of metformin to reduce delirium risk and mortality: a retrospective cohort study, Aging (2022). DOI: 10.18632/aging.204393

 

Researchers find that brains with more vitamin D function better

An estimated 55 million people worldwide live with dementia, a number that's expected to rise as the global population ages. To find treatments that can slow or stop the disease, scientists need to better understand the factors that can cause dementia.

17 jan 2023--Researchers at Tufts University have completed the first study examining levels of vitamin D in brain tissue, specifically in adults who suffered from varying rates of cognitive decline. They found that members of this group with higher levels of vitamin D in their brains had better cognitive function. The study was published December 7 in Alzheimer's & Dementia.

"This research reinforces the importance of studying how food and nutrients create resilience to protect the aging brain against diseases such as Alzheimer's disease and other related dementias," said senior and corresponding author Sarah Booth, director of the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts and lead scientist of the HNRCA's Vitamin K Team.

Vitamin D supports many functions in the body, including immune responses and maintaining healthy bones. Dietary sources include fatty fish and fortified beverages (such as milk or orange juice); brief exposure to sunlight also provides a dose of vitamin D.

"Many studies have implicated dietary or nutritional factors in cognitive performance or function in older adults, including many studies of vitamin D, but all of them are based on either dietary intakes or blood measures of vitamin D," said lead author Kyla Shea, a scientist on the Vitamin K Team and an associate professor at the Friedman School of Nutrition Science and Policy at Tufts. "We wanted to know if vitamin D is even present in the brain, and if it is, how those concentrations are linked to cognitive decline."

Booth, Shea, and their team examined samples of brain tissue from 209 participants in the Rush Memory and Aging Project, a long-term study of Alzheimer's disease that began in 1997. Researchers at Rush University assessed the cognitive function of the participants, older people with no signs of cognitive impairment, as they aged, and analyzed irregularities in their brain tissue after death.

In the Tufts study, researchers looked for vitamin D in four regions of the brain—two associated with changes linked to Alzheimer's disease, one associated with forms of dementia linked to blood flow, and one region without any known associations with cognitive decline related to Alzheimer's disease or vascular disease. They found that vitamin D was indeed present in brain tissue, and high vitamin D levels in all four regions of the brain correlated with better cognitive function.

However, the levels of vitamin D in the brain didn't associate with any of the physiological markers associated with Alzheimer's disease in the brain studied, including amyloid plaque buildup, Lewy body disease, or evidence of chronic or microscopic strokes. This means it's still unclear exactly how vitamin D might affect brain function.

"Dementia is multifactorial, and lots of the pathological mechanisms underlying it have not been well characterized," Shea says. "Vitamin D could be related to outcomes that we didn't look at yet, but plan to study in the future."

Vitamin D is also known to vary between racial and ethnic populations, and most of the participants in the original Rush cohort were white. The researchers are planning followup studies using a more diverse group of subjects to look at other brain changes associated with cognitive decline. They hope their work leads to a better understanding of the role vitamin D may play in staving off dementia.

However, experts caution people not to use large doses of vitamin D supplements as a preventive measure. The recommended dose of vitamin D is 600 IU for people 1-70 years old, and 800 IU for those older—excessive amounts can cause harm, and have been linked to the risk of falling.

"We now know that vitamin D is present in reasonable amounts in human brains, and it seems to be correlated with less decline in cognitive function," Shea says. "But we need to do more research to identify the neuropathology that vitamin D is linked to in the brain before we start designing future interventions."

More information: Brain Vitamin D Forms, Cognitive Decline and Neuropathology in Community-dwelling Older Adults, Alzheimer s & Dementia (2022). DOI: 10.1002/alz.12836