Gut Microbiome Implicated in Healthy Aging and Longevity

The gut microbiome is an integral component of the body, but its importance in the human aging process is unclear. Institute for Systems Biology (ISB) researchers and their collaborators have identified distinct signatures in the gut microbiome that are associated with either healthy or unhealthy aging trajectories, which in turn predict survival in a population of older individuals. The work was just published in the journal Nature Metabolism,

Data from over 9,000 people reveal a distinct gut microbiome signature that is associated with healthy aging and survival in the latest decades of life.

The research team analyzed gut microbiome, phenotypic and clinical data from over 9,000 people – between the ages of 18 and 101 years old – across three independent cohorts. The team focused, in particular, on longitudinal data from a cohort of over 900 community-dwelling older individuals (78-98 years old), allowing them to track health and survival outcomes.

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Exercise May Help Slow Memory Loss for People Living With Alzheimer’s Dementia

Exercise may reduce decline in global cognition in older adults with mild-to-moderate AD dementia. Aerobic exercise did not show superior cognitive effects to stretching in our pilot trial, possibly due to the lack of power. ASU Edson College of Nursing and Health Innovation Professor Fang Yu led a pilot randomized control trial that included 96 older adults living with mild to moderate Alzheimer’s dementia.

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Participants were randomized to either a cycling (stationary bike) or stretching intervention for six months. Using the Alzheimer’s Disease Assessment Scale-Cognition (ADAS-Cog) to assess cognition, the results of the trial were substantial.

The six-month change in ADAS-Cog was 1.0±4.6 (cycling) and 0.1±4.1 (stretching), which were both significantly less than the expected 3.2±6.3-point increase observed naturally with disease progression.

“Our primary finding indicates that a six-month aerobic exercise intervention significantly reduced cognitive decline in comparison to the natural course of changes for Alzheimer’s dementia. However, we didn’t find a superior effect of aerobic exercise to stretching, which is likely due to the pilot nature of our trial. We don’t have the statistical power to detect between-group differences, there was substantial social interaction effect in the stretching group, and many stretching participants did aerobic exercise on their own.” Yu said.

The findings are described in a recently published article, Cognitive Effects of Aerobic Exercise in Alzheimer’s Disease: A Pilot Randomized Controlled Trial, in the Journal of Alzheimer’s Disease.

Yu says their results are encouraging and support the clinical relevance of promoting aerobic exercise in individuals with Alzheimer’s dementia to maintain cognition.

“Aerobic exercise has a low profile of adverse events in older adults with Alzheimer’s dementia as demonstrated by our trial,” said Yu. “Regardless of its effect on cognition, the current collective evidence on its benefits supports the use of aerobic exercise as an additional therapy for Alzheimer’s disease.”

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More deaths in England and Scotland may be due to obesity and excess body fat than smoking – Study

While the focus of the following research was overseas, the U.S. suffers from obesity and excess body fat to a large extent also.

Obesity and excess body fat may have contributed to more deaths in England and Scotland than smoking since 2014, according to research published in the open access journal BMC Public Health.

Between 2003 and 2017 the percentage of deaths attributable to smoking are calculated to have decreased from 23.1% to 19.4% while deaths attributable to obesity and excess body fat are calculated to have increased from 17.9% to 23.1%. The authors estimate that deaths attributable to obesity and excess body fat overtook those attributable to smoking in 2014.

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Jill Pell, at the University of Glasgow, United Kingdom, the corresponding author said: “For several decades smoking has been a major target of public health interventions as it is a leading cause of avoidable deaths. As a result, the prevalence of smoking has fallen in the United Kingdom. At the same time the prevalence of obesity has increased. Our research indicates that, since 2014, obesity and excess body fat may have contributed to more deaths in England and Scotland than smoking.”

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Artificial ‘brain’ reveals why we can’t always believe our eyes

A computer network closely modelled on part of the human brain is enabling new insights into the way our brains process moving images – and explains some perplexing optical illusions.

By using decades’ worth of data from human motion perception studies, researchers have trained an artificial neural network to estimate the speed and direction of image sequences.

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The new system, called MotionNet, is designed to closely match the motion-processing structures inside a human brain. This has allowed the researchers to explore features of human visual processing that cannot be directly measured in the brain.

Their study, published in the Journal of Vision, uses the artificial system to describe how space and time information is combined in our brain to produce our perceptions, or misperceptions, of moving images.

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Weekend funnies …

These tickled my fancy. I hope they do the same for you.

Tony

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Employment may slow memory decline for women – NIA

Working in the paid labor workforce may have cognitive benefits later in life for U.S. women. For a study supported in part by the National Institute on Aging (NIA), researchers looked at the influence of social, employment, and gender-related factors on memory decline with implications for dementia risk. Their findings, recently published in Neurology, show that women in the workforce during early adulthood and midlife experienced slower rates of memory decline than those who had not worked for pay.

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A team of University of California (UC), Los Angeles; UC San Francisco; Harvard; and Boston College researchers analyzed the employment patterns, family structure, and demographic characteristics of U.S. women. More than 6,000 women at least age 55 in the Health and Retirement Study reported their past work-family statuses of employment, marriage, and parenthood between ages 16 and 50. They also participated in word recall memory assessments every two years over an average of 12 years. The study team then evaluated rates of later-life memory decline, which is a measure associated with dementia.

The average rate of memory decline after age 60 was slower for women who had worked, regardless of marriage and parenthood status. Taking time off from work when their children were young did not seem to decrease the cognitive benefit in married working mothers. Among nonworking mothers, rates of memory decline were similar for single and married women. Demographic characteristics, such as race, childhood socioeconomic status, and level of education, did not explain the relationship between work-family status and memory decline.

This study adds to evidence that participation in the workforce may be a protective factor for cognitive health later in life. The researchers did not look at volunteer work, the types of paid labor among women, or possible differences among genders. Future research on effects of participating in the workforce, such as cognitive stimulation and social engagement, may help explain how employment can decrease the rate of memory loss.

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New Prostate Cancer Test Could Avoid Unnecessary Biopsies – Study

A urine test based on University of Michigan Rogel Cancer Center research could have avoided one third of unnecessary prostate cancer biopsies while failing to detect only a small number of cancers, according to a validation study that included more than 1,500 patients. The findings appear in the March issue of the Journal of Urology.

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The MyProstateScore test, which is being commercialized by LynxDX, a U-M startup company, measures levels of cancer-specific genes in a patient’s urine. It is based on U-M research that discovered that half of all prostate tumors harbor a certain genetic anomaly in which the genes TMPRSS2 and ERG relocate on a chromosome and fuse together — creating an on-switch for prostate cancer development.

Currently, one of doctors’ best methods for detecting prostate cancer is a blood test for prostate-specific antigen, commonly known as the PSA test. Elevated PSA levels may indicate cancer, but the majority of men with an elevated PSA do not actually have prostate cancer.

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Genetic basis for daytime napping

How often a person takes daytime naps, if at all, is partly regulated by their genes, according to new research led by investigators at Massachusetts General Hospital (MGH) and published in Nature Communications. In this study, the largest of its kind ever conducted, the MGH team collaborated with colleagues at the University of Murcia in Spain and several other institutions to identify dozens of gene regions that govern the tendency to take naps during the day. They also uncovered preliminary evidence linking napping habits to cardiometabolic health.

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“Napping is somewhat controversial,” says Hassan Saeed Dashti, PhD, RD, of the MGH Center for Genomic Medicine, co-lead author of the report with Iyas Daghlas, a medical student at Harvard Medical School (HMS). Dashti notes that some countries where daytime naps have long been part of the culture (such as Spain) now discourage the habit. Meanwhile, some companies in the United States now promote napping as a way to boost productivity. “It was important to try to disentangle the biological pathways that contribute to why we nap,” says Dashti. 

Previously, co-senior author Richa Saxena, PhD, principal investigator at the Saxena Lab at MGH, and her colleagues used massive databases of genetic and lifestyle information to study other aspects of sleep. Notably, the team has identified genes associated with sleep duration, insomnia, and the tendency to be an early riser or “night owl.” To gain a better understanding of the genetics of napping, Saxena’s team and co-senior author Marta Garaulet, PhD, of the department of Physiology at the University of Murcia, performed a genome-wide association study (GWAS), which involves rapid scanning of complete sets of DNA, or genomes, of a large number of people. The goal of a GWAS is to identify genetic variations that are associated with a specific disease or, in this case, habit.

For this study, the MGH researchers and their colleagues used data from the UK Biobank, which includes genetic information from 452,633 people. All participants were asked whether they nap during the day “never/rarely,” “sometimes” or “usually.” The GWAS identified 123 regions in the human genome that are associated with daytime napping. A subset of participants wore activity monitors called accelerometers, which provide data about daytime sedentary behavior, which can be an indicator of napping. This objective data indicated that the self-reports about napping were accurate. “That gave an extra layer of confidence that what we found is real and not an artifact,” says Dashti.

Several other features of the study bolster its results. For example, the researchers independently replicated their findings in an analysis of the genomes of 541,333 people collected by 23andMe, the consumer genetic-testing company. Also, a significant number of the genes near or at regions identified by the GWAS are already known to play a role in sleep. One example is KSR2, a gene that the MGH team and collaborators had previously found plays a role in sleep regulation.

Digging deeper into the data, the team identified at least three potential mechanisms that promote napping:

– Sleep propensity: Some people need more shut-eye than others.

– Disrupted sleep: A daytime nap can help make up for poor quality slumber the night before.

– Early morning awakening: People who rise early may “catch up” on sleep with a nap.

“This tells us that daytime napping is biologically driven and not just an environmental or behavioral choice,” says Dashti. Some of these subtypes were linked to cardiometabolic health concerns, such as large waist circumference and elevated blood pressure, though more research on those associations is needed. “Future work may help to develop personalized recommendations for siesta,” says Garaulet. 

Furthermore, several gene variants linked to napping were already associated with signaling by a neuropeptide called orexin, which plays a role in wakefulness. “This pathway is known to be involved in rare sleep disorders like narcolepsy, but our findings show that smaller perturbations in the pathway can explain why some people nap more than others,” says Daghlas.

Saxena is the Phyllis and Jerome Lyle Rappaport MGH Research Scholar at the Center for Genomic Medicine and an associate professor of Anesthesia at HMS.

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Prediabetes may be linked to worse brain health

People with prediabetes, whose blood sugar levels are higher than normal, may have an increased risk of cognitive decline and vascular dementia, according to a new study led by University College London (UCL) researchers.

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For the study, published in the journal Diabetes, Obesity and Metabolism, researchers analyzed data from the UK Biobank of 500,000 people aged 58 years on average, and found that people with higher than normal blood sugar levels were 42% more likely to experience cognitive decline over an average of four years, and were 54% more likely to develop vascular dementia over an average of eight years (although absolute rates of both cognitive decline and dementia were low).

The associations remained true after other influential factors had been taken into account – including age, deprivation, smoking, BMI and whether or not participants had cardiovascular disease.

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Watch your heart rate, but don’t obsess about it – AHA

Keeping track of your heart rate is probably a good thing. Obsessing about it probably isn’t, according to the American Heart Association.

That’s one drawback of the increasing popularity of wearable devices that constantly monitor heart rates, said Dr. Tracy Stevens, a cardiologist at Saint Luke’s Mid America Heart Institute in Kansas City, Missouri.

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“I’ve had people suffer significant injuries when they’re trying to check their heart rate while exercising,” she said. “They take a hand off their treadmill and shoot right off the back and fall off.”

Even without a monitor, the preoccupation can have consequences.

“They’ll push too hard on their carotid arteries to check their pulse, which instigates a reflex that drops their blood pressure, and they pass out,” Stevens said. People shouldn’t put “too much emphasis on a number.”

A 2013 study published in the journal Heart of nearly 3,000 men in Denmark showed the risk of death increased by 16% for every 10 beats per minute increase in resting heart rate. But Stevens said she is far more focused on high blood pressure, obesity, smoking and other risk factors for heart disease.

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Exhaled respiratory droplets increase in number with the onset of COVID-19 infection — and with aging and obesity

Superspreading events have distinguished the COVID-19 pandemic from the early outbreak of the disease. Now, research from Harvard University, Tulane University, MIT and Massachusetts General Hospital finds that a critical factor in these and other transmission events is the propensity of certain individuals to exhale large numbers of small respiratory droplets. The researchers found that age, obesity and COVID-19 infection all correlate with a propensity to breathe out more respiratory droplets.

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Understanding the source and variance of respiratory droplet generation may lead to effective approaches to reducing COVID-19 infection and transmission.

The study was published in the Proceedings of the National Academy of Sciences.

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Weekend funnies

I hope you had a pleasant Valentine’s Day. I can’t believe we are now past the middle of February 2021 already.

I wanted to finish with this little trick of the eye. Do you see a dog running out of the woods or a man running in?

Tony

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Vegetables: to Cook or Not to Cook – Tufts

Vegetables are an excellent source of vitamins, minerals, phytochemicals, and fiber, and health-conscious consumers naturally want to know how to get the most nutritional impact from these powerful foods. “Nutritionally, there are pluses and minuses to cooking vegetables,” says Helen Rasmussen, PhD, RD, a senior research dietitian at Tufts’ Jean Mayer USDA Human Nutrition Research Center on Aging. For example, cooking carrots reduces levels of vitamin C (which plays an important role in maintaining collagen, the glue that holds cells together) but increases availability of beta-carotene, a precursor of vitamin A (which plays an important role in vision, reproduction, bone growth, and regulating the immune system).

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Reduced Concentration. Some nutrients will be lost in any cooking method. “Some vitamins are not very stable,” says Rasmussen. “The longer a food is exposed to heat, the more vitamin C levels are reduced, for example.” The concentration of some nutrients is particularly affected by cooking in water. “Vitamin C and B vitamins are water soluble, as are certain phytochemicals, like flavonoids,” says Jeffrey B. Blumberg, PhD, a research professor at Tufts’ Friedman School of Nutrition Science and Policy. “They leach out into water when the vegetables are boiled.” Blumberg recommends eating produce high in these nutrients (like broccoli, kale, and bell peppers) raw. “When you do cook them, try methods like steaming, blanching, sauting, roasting, or microwaving, which use little water,” says Blumberg. If you do boil your vegetables in excess water, Rasmussen recommends using that water to make broths or sauces, rather than pouring nutrients down the drain.

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People with dementia at higher risk for COVID-19 – Study

Patients with dementia were at a significantly increased risk for COVID-19 — and the risk was higher still for African Americans with dementia, according to a study led by Case Western Reserve University researchers.

Reviewing electronic health records of 61.9 million adults in the United States, researchers found the risk of contracting COVID-19 was twice as high for patients with dementia than for those without it — while among those with dementia, African Americans had close to three times the risk of being infected with COVID-19 as Caucasians did.

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In addition, patients with dementia who contracted COVID-19 had significantly worse outcomes in terms of hospitalizations and deaths than those who had COVID-19 but not dementia.

The study was published Feb. 9 by the peer-reviewed Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association and highlights the need to protect people with dementia — particularly African Americans — as part of the strategy to control the pandemic.

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Blink! The Link between Aerobic Fitness and Cognition

Although exercise is known to enhance cognitive function and improve mental health, the neurological mechanisms of this link are unknown. Now, researchers from Japan have found evidence of the missing link between aerobic fitness and cognitive function.


In a study published in Medicine & Science in Sports & Exercise, researchers from the University of Tsukuba revealed that spontaneous eye blink rate (sEBR), which reflects activity of the dopamine system, could be used to understand the connection between cognitive function and aerobic fitness.

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The dopaminergic system is known to be involved in physical activity and exercise, and previous researchers have proposed that exercise-induced changes in cognitive function might be mediated by activity in the dopaminergic system. However, a marker of activity in this system was needed to test this hypothesis, something the researchers at the University of Tsukuba aimed to address.

“The dopaminergic system is associated with both executive function and motivated behavior, including physical activity,” says first author of the study Ryuta Kuwamizu. “We used sEBR as a non-invasive measure of dopaminergic system function to test whether it could be the missing link between aerobic fitness and cognitive function.”

To do this, the researchers asked healthy participants to undergo a measure of sEBR, a test of cognitive function, and an aerobic fitness test. They also measured brain activity during the cognitive task using functional near-infrared spectroscopy.

“As expected, we found significant correlations between aerobic fitness, cognitive function, and sEBR,” explains Professor Hideaki Soya, senior author. “When we examined these relationships further, we found that the connection between higher aerobic fitness and enhanced cognitive function was mediated in part by dopaminergic regulation.”

Furthermore, activity in the left dorsolateral prefrontal cortex (l-DLPFC) during the cognitive task was the same or lower in participants with higher sEBR compared with lower sEBR, even though those with higher sEBR appeared to have greater executive function, and thus higher neural efficiency.

“Although previous studies have indicated that aerobic fitness and cognitive function are correlated, this is the first to provide a neuromodulatory basis for this connection in humans. Our data indicate that dopamine has an essential role in linking aerobic fitness and cognition,” says first author Kuwamizu.

Given that neural efficiency in the l-DLPFC is a known characteristic of the dopaminergic system that has been observed in individuals with higher fitness and executive function, it is possible that neural efficiency in this region partially mediates the association between aerobic fitness and executive function. Furthermore, physical inactivity may be related to dopaminergic dysfunction. This information provides new directions for research regarding how fitness affects the brain, which may lead to improved exercise regimens. For instance, exercise that specifically focuses on improving dopaminergic function may particularly boost motivation, mood, and mental function.

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Biological causes of muscle weakness in later life

A new large scale genetic analysis has found biological mechanisms that contribute to making people more susceptible to muscle weakness in later life, finding that diseases such as osteoarthritis and diabetes may play a large role in susceptibility.

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As we get older we lose muscle strength, and in some people this severe weakness impacts their ability to live everyday lives, a condition called sarcopenia. Around 10 per cent of people over 50 experience sarcopenia. Many causes thought to impact likelihood of developing this weakness, which is linked to higher death rates.

In a genetic analysis of over 250,000 people aged over 60 from UK Biobank and 21 other cohorts, an international team led by researchers at the University of Exeter looked at hand grip strength, using thresholds of loss of muscle function derived from international definitions of sarcopenia.

The team, including collaborators from the USA and the Netherlands, then conducted a genetic analysis, and found specific biological mechanisms push some people towards sarcopenia, while protecting others. The study, published in Nature Communications identified 15 areas of the genome, or loci, associated with muscle weakness, including 12 loci not implicated in previous analyses of continuous measures of grip strength.

Biomarkers in the blood including red blood cells and inflammation may also share causal pathways with sarcopenia. Together, these results highlight specific areas for intervention or for identifying those at most risk.

Lead author Garan Jones said: “The strongest associations we found were close to regions of the genome regulating the immune system, and growth and development of the muscloskeletal system. However, we also discovered associations with regions not previously known to be linked to muscloskeletal traits.

“We found that our analysis of muscle weakness in older people shared common genetic pathways with metabolic diseases such as type-2 diabetes, and auto-immune conditions such as osteoarthritis and rheumatoid arthritis. In subgroups of people with increased risk of these conditions, sarcopenia may be a key outcome to look out for and prevent.

“We hope that by understanding the genetic contributions to muscle weakness with age, we will be able to highlight possible therapeutic interventions earlier in life, which would lead to a happier and healthier old age.”

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