Category: Ageing

Categories : Ageing NeurologyTags :

Instead of Dying, Motor Neurons Just Lose Connectivity with Age

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A new study published in the Journal of Clinical Investigation Insight offers a blueprint to help scientists prevent and reverse motor deficits that occur in old age. Their findings showed that loss of connectivity of motor neurons in the spinal cord – not the death of those neurons, as was previously thought – is what impairs voluntary movements during aging.

As humans age, tasks that require coordinated motor skills, such as navigating stairs or writing a letter, become increasingly difficult to perform. Reduced mobility caused by aging is strongly associated with adverse health outcomes and a diminished quality of life.

Researchers at Brown University led by Gregorio Valdez, an associate professor of molecular biology, cell biology and biochemistry, discovered that motor neurons start to have fewer synapses.

“This is an important fundamental discovery because it tells us that treatments are possible to prevent and reverse motor deficits that occur as we age,” said Valdez, who is affiliated with both the Center for Translational Neuroscience and the Center for Alzheimer’s Disease Research at the Carney Institute and Brown’s Center on the Biology of Aging. “The primary hardware, motor neurons, are spared by aging. If we can figure out how to keep synapses from degenerating, or mimic their actions using pharmacological interventions, we may be able to treat motor issues in the elderly that often lead to injuries due to falls.”

For the study, researchers examined spinal motor neurons in three species, including humans, rhesus monkeys and mice.

“These findings revealed that, as individuals age, motor neurons lose many of the connections that direct their function,” said Ryan Castro, first author of the study, who earned a PhD in neuroscience from Brown in 2022.    

Because of their critical function, Valdez said, the loss of either motor neurons or their synapses would impair voluntary movements. 

The number and size of motor neurons do not significantly change during aging, the researchers discovered. However, they undergo other processes that contribute to aging.

“Aging causes motor neurons to engage in self-destructive behaviour,” Valdez said. “While motor neurons do not die in old age, they progressively increase expression of molecules that cause degeneration of their own synapses and cause glial cells to attack neurons, and that increases inflammation.” 

Some of these aging-related genes and pathways are also found altered in motor neurons affected with amyotrophic lateral sclerosis (ALS).

The researchers now plan to pursue studies to target molecular mechanisms they found altered in motor neurons that could be responsible for the loss of their own synapses with advancing age.  

Source: Brown University

Categories : Ageing Diseases, Syndromes and ConditionsTags :

Possible Explanation for Why More Men Develop Hearing Loss in Old Age

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A new study led by Yale School of Medicine scientists and published in BMC has pinpointed why some adults – by some estimates, at least 50% of the population after 75 years of age – develop hearing problems.

While congenital hearing impairment – usually presenting in childhood – result from rare mutations, hearing problems in adults are likely due to the cumulative effect of polygenic risk and environmental factors.

Recent genome-wide association studies have uncovered several risk genes that are implicated in hearing problems in adults, however some factors still have not adequately been investigated by large-scale genetic studies.

For instance, there is limited information about why hearing problems among older adults are more common, more severe, and with earlier onset in men than in women. It is uncertain how hearing-related polygenic risk translates among people of diverse ancestral backgrounds.

While environmental risk factors such as noise exposure and tobacco smoking are known to increase the risk of hearing problems, the molecular mechanisms underlying these associations are unclear.

Researchers sampled nearly 750 000 adults and identified 54 risk variants – including 12 novel variants – that could contribute to hearing problems. They also highlighted how hormonal regulation may play a role in the differences between hearing problems in men and women.

Analysing multiple ancestry groups, the researchers demonstrated that polygenic risk in hearing problems is shared across human populations. They also determined genes involved in brain development interact with sex, noise pollution, and tobacco smoking in relation to their associations with hearing problems.

“Our results support that large-scale genetic studies are useful instruments to understand the biology and the epidemiology of hearing problems in adults,” said Renato Polimanti, PhD, associate professor of psychiatry at Yale School of Medicine and senior author of the study.

Overall, the findings contribute to identifying possible molecular targets for drug development and define novel strategies to identify older adults at risk of losing their hearing.

The study could lead to changes in how older adults with hearing problems are assessed and treated. Hearing loss can impair communications, and that can result in social isolation with major health, psychosocial, and economic consequences, reducing the quality of life of those affected.

Source: Yale University

Categories : Ageing Diet and NutritionTags :

Can Low-carbohydrate or Low-fat Diets Extend Lifespan?

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Better diets are needed to address the macronutritional needs of an ageing population. Short-term clinical trials have demonstrated the health benefits of low-carbohydrate diets (LCDs) and low-fat diets (LFDs) for weight loss and heart protection. Now a study published in the Journal of Internal Medicine looks at the effects of these diets on mortality in middle-aged and older adults.

In the study of 371 159 individuals aged 50 to 71 years, 165 698 deaths occurred over a median follow-up of 23.5 years.

A healthy LFD – characterised by low intake of saturated fat and high intakes of plant protein and high-quality carbohydrates – was related to fewer deaths from all causes, from cardiovascular diseases, and from cancers. In contrast, an overall LCD and an unhealthy LCD were associated with significantly higher total, cardiovascular, and cancer mortality rates. A healthy LCD was associated with slightly lower death rates.

“Our results support the importance of maintaining a healthy LFD with less saturated fat in preventing all-cause and cause-specific mortality among middle-aged and older people,” the authors wrote.

Source: Wiley

Categories : AgeingTags :

Grey Hairs Result from Stem Cells Getting ‘Stuck’

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Certain stem cells have a unique ability to move between growth compartments in hair follicles, but get stuck as people age and so lose their ability to mature and maintain hair colour, a new Nature study shows.

Led by researchers from NYU Grossman School of Medicine, the new work focused on cells in the skin of mice and also found in humans called melanocyte stem cells, or McSCs. Hair colour is controlled by whether nonfunctional but continually multiplying pools of McSCs within hair follicles get the signal to become mature cells that make the protein pigments responsible for color.

The new study showed that McSCs are remarkably plastic. This means that during normal hair growth, such cells continually move back and forth on the maturity axis as they transit between compartments of the developing hair follicle. It is inside these compartments where McSCs are exposed to different levels of maturity-influencing protein signals.

Specifically, the research team found that McSCs transform between their most primitive stem cell state and the next stage of their maturation, the transit-amplifying state, and depending on their location.

The researchers found that as hair ages, sheds, and then repeatedly grows back, increasing numbers of McSCs get stuck in the stem cell compartment called the hair follicle bulge. There, they remain, do not mature into the transit-amplifying state, and do not travel back to their original location in the germ compartment, where WNT proteins would have prodded them to regenerate into pigment cells.

“Our study adds to our basic understanding of how melanocyte stem cells work to colour hair,” said study lead investigator Qi Sun, PhD, a postdoctoral fellow at NYU Langone Health. “The newfound mechanisms raise the possibility that the same fixed-positioning of melanocyte stem cells may exist in humans. If so, it presents a potential pathway for reversing or preventing the graying of human hair by helping jammed cells to move again between developing hair follicle compartments.”

Researchers say McSC plasticity is not present in other self-regenerating stem cells, such as those making up the hair follicle itself, which are known to move in only one direction along an established timeline as they mature. For example, transit-amplifying hair follicle cells never revert to their original stem cell state. This helps explain in part why hair can keep growing even while its pigmentation fails, says Sun.

Earlier work by the same research team at NYU showed that WNT signalling was needed to stimulate the McSCs to mature and produce pigment. That study had also shown that McSCs were many trillions of times less exposed to WNT signalling in the hair follicle bulge than in the hair germ compartment, which is situated directly below the bulge.

In the latest experiments in mice whose hair was physically aged by plucking and forced regrowth, the number of hair follicles with McSCs lodged in the follicle bulge increased from 15% before plucking to nearly half after forced aging. These cells remained incapable of regenerating or maturing into pigment-producing melanocytes.

The stuck McSCs, the researchers found, ceased their regenerative behaviour as they were no longer exposed to much WNT signalling and hence their ability to produce pigment in new hair follicles, which continued to grow.

By contrast, other McSCs that continued to move back and forth between the follicle bulge and hair germ retained their ability to regenerate as McSCs, mature into melanocytes, and produce pigment over the entire study period of two years.

“It is the loss of chameleon-like function in melanocyte stem cells that may be responsible for greying and loss of hair colour,” said study senior investigator Mayumi Ito, PhD, a professor in the Ronald O. Perelman Department of Dermatology and the Department of Cell Biology at NYU Langone Health.

“These findings suggest that melanocyte stem cell motility and reversible differentiation are key to keeping hair healthy and coloured,” said Ito, who is also a professor in the Department of Cell Biology at NYU Langone.

Ito says the team has plans to investigate means of restoring motility of McSCs or of physically moving them back to their germ compartment, where they can produce pigment.

Source: NYU Langone Health / NYU Grossman School of Medicine

Categories : Ageing Skeletal SystemTags :

Flipping the Switch on Osteoporosis with Epigenetic Discovery

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Van Andel Institute scientists have pinpointed a key driver of low bone density, a discovery that may lead to improved treatments with fewer side effects for women with osteoporosis. Their findings appear in the journal Science Advances.

Their research reveals that loss of an epigenetic modulator, KDM5C, preserves bone mass in mice. KDM5C works by altering epigenetic ‘marks’, switches that ensure the instructions written in DNA are read in the right time and place.

Several medications are approved to treat osteoporosis but fears of rare, severe side effects often are a barrier for their use. Treatments that leverage the hormone oestrogen also are available, but are only recommended for low-dose, short-term use due in part to associations with cancer risk.

It is well-established that women experience disproportionately lower bone mass than men throughout their lives. Loss of bone mass accelerates with menopause, increasing the risk of osteoporosis and associated fractures for women as they age.

To figure out why this happens, VAI Associate Professors Connie M. Krawczyk, PhD, and Tao Yang, PhD, and their teams looked at the differences in the ways bone is regulated in male and female mice, which share many similarities with humans and are important models for studying health and disease. They focused on osteoclasts, which help maintain bone health by breaking down and recycling old bone.

“Osteoporosis is a common disease that can have debilitating outcomes,” Yang said. “KDM5C is a promising target to treat low bone mass in women because it is highly specific. We’re hopeful that our findings will contribute to improved therapies.”

The researchers found reducing KDM5C disrupted cellular energy production in osteoclasts, which slowed down the recycling process and preserved bone mass. Importantly, KDM5C is linked to X chromosomes, which means it is more active in females than in males.

“Lowering KDM5C levels is like flipping a switch to stop an overactive recycling process. The result is more bone mass, which ultimately means stronger bones,” Krawczyk said. “We’re very excited about this work and look forward to carrying out future studies to refine our findings. At the end of the day, we hope these insights make a difference for people with osteoporosis.”

Source: Van Andel Research Institute

Categories : Ageing Injury & TraumaTags :

Researchers Develop 5-factor Model for Nursing Home Fall Risks

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In research published in the Journal of the American Geriatrics Society, investigators developed and validated models that can predict the risk of fall-related injuries (FRI) in nursing home residents based on routinely collected clinical data.

The researchers conducted retrospective cohort study of long-stay US nursing home residents (mean age 85 years, 69.6% female) between January 1, 2016 and December 31, 2017 (n = 733 427) using Medicare claims and Minimum Data Set v3.0 clinical assessments. Predictors of FRIs were selected through statistical methods, from an original set of 70 predictors. To come up with a useful clinical tool, they calculated a score using the five strongest predictors in the model.

Within 2 years of follow-up, 6% of residents experienced one or more FRI. The prediction models achieved good discrimination and excellent calibration for accurately estimating individuals’ six-month and two-year risk of fall-related injuries. In the clinical tool to predict 2-year risk, the five characteristics included independence in activities of daily living (ADLs) (HR 2.27; 95% CI 2.14–2.41) and a history of non-hip fracture (HR 2.02; 95% CI 1.94–2.12). Performance results were similar in the validation sample.

“These models can be used by researchers and clinicians to accurately determine patient risk for fall-related injuries using routinely collected clinical assessment data,” the authors wrote. “In nursing homes, these models should be used to target preventive strategies.”

Source: Wiley

Categories : Ageing CancerTags :

Studying People with Early Grey Hair Leads to Sarcoma Clue

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A new study from Copenhagen University may have found a new treatment for the sickest patients with sarcomas. Sarcomas are cancer tumours found in bones, muscles or fatty tissue. Sarcomas are cancer tumours found in bones, muscles or fatty tissue. Complex and difficult to treat, it is a rare type of cancer seen in only one per cent of cancer patients.

Researchers noticed that people with certain rare disorders were both more likely to have early grey hairs and wrinkles as well as having a high risk of developing cancer.

“We have learned that sarcoma patients whose cancer cells have a high expression of the cep135 protein are worse off. But inhibiting a gene called plk1 also inhibits growth of the sarcoma cells, and this suggests that we can target the treatment of the sickest sarcoma patients,” says Associate Professor Morten Scheibye-Knudsen, lead researcher of the new study which is published in Nature.

Methods for identifying sarcoma patients’ prognoses are already available, as are different forms of treatment. But the new study has identified a new method.

“This is a new way of stratifying and possibly a new and better way of treating sarcoma. And the introduction of yet another method is always good news to patients. Because no two cancers are alike. Ideally, treatment should always be tailored to the individual patient,” Morten Scheibye-Knudsen stresses.

He hopes other researchers with access to the necessary test facilities will study his results in more detail and eventually design a new treatment. If the method turns out to work, he believes a new treatment may be available to patients in five to 10 years.

Grey hair, wrinkles and loss of fatty tissue at an early age

Morten Scheibye-Knudsen and his colleagues started out by studying patients suffering from the rare neurological disorders Werner’s syndrome, Nijmegen breakage syndrome and Ataxia-telangiectasia syndrome.

These patients experience symptoms of early ageing such as grey hair, wrinkles and loss of fatty tissue – and they have a high risk of developing cancer at an early age.

“Age-associated diseases such as cancer is one of my main areas of interest as a researcher at the Center for Healthy Aging. As we grow older, a lot of things happen to the body, and determining causality can be difficult. But in people suffering from, eg Werner’s syndrome, it is easier to see which genes are responsible for which processes. This gives us a molecular handle, so to speak,” says Morten Scheibye-Knudsen.

In order to establish why these patients develop cancer at an early age, the researchers compared gene expressions across the three disorders. Here they worked together with the company Insilico Medicine, whose large Pandaomics platform made it possible to identify gene mutations in thousands of different disorders. It turned out that cep135 is a common denominator for the cancer genes of the three disorders.

“This made us study the gene expressions of various cancers, and we learned that cep135 is associated with high mortality in, inter alia, sarcoma, but also in bladder cancer. Sarcoma was particularly interesting, as many Werner’s syndrome patients develop sarcoma,” explains Morten Scheibye-Knudsen.

Finally, the researchers sought to find ways to inhibit the sarcoma. Cep135 is not a useful target, as it is a so-called structural protein, which are difficult to target. Instead, the researchers learned that by inhibiting the plk1 gene they were able to target the sarcoma.

“The study indicates that we can use genetic diseases that exhibit accelerated aging to identify new treatment targets. In this study, we investigated cancer, but the method can in principle be used for all age-related diseases such as dementia, cardiovascular diseases and others,” says Morten Scheibye-Knudsen.

Source: University of Copenhagen

Categories : Ageing Neurodegenerative DiseasesTags :

Difficulty Falling Asleep Linked to Developing Dementia

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Old man
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Adding to the growing body of evidence on sleep disturbances and cognitive impairment, new research published in the American Journal of Preventive Medicine, finds significant links between three measures of sleep disturbance and the risk for developing dementia over a 10-year period. Difficulties falling asleep were linked to higher risk, but not falling asleep again after waking.

The results associate sleep-initiation insomnia (trouble falling asleep within 30 min) and sleep medication use with higher dementia risk. An additional, surprising finding was that people who reported having sleep-maintenance insomnia (trouble falling back to sleep after waking) were less likely to develop dementia over the course of the study.

“We expected sleep-initiation insomnia and sleep medication usage to increase dementia risk, but we were surprised to find sleep-maintenance insomnia decreased dementia risk,” explained lead investigator Roger Wong, PhD, MPH, MSW, an Assistant Professor in the Department of Public Health and Preventive Medicine, SUNY Upstate Medical University. “The motivation behind this research was prompted on a personal level. My father has been experiencing chronic sleep disturbances since the COVID pandemic began, and I was concerned how this would affect his cognition in the future. After reading the existing literature, I was surprised to see mixed findings on the sleep-dementia relationship, so I decided to investigate this topic.”

This research is novel because it is the first to examine how long-term sleep disturbance measures are associated with dementia risk using a nationally representative US older adult sample. Previous research has associated REM sleep behavior, sleep deprivation (less than five hours of sleep), and the use of short-acting benzodiazepines with cognitive decline. Their results for sleep-maintenance insomnia support other recent studies using smaller, separate data samples.

This study used 10 annual waves (2011–2020) of prospective data from the National Health and Aging Trends Study (NHATS), a longitudinal panel study that surveys a nationally representative sample of Medicare beneficiaries aged 65 years and older within the USA. This study included only people who were dementia-free at baseline in 2011.

While the mechanism for decreased dementia risk among those with sleep-maintenance insomnia is still unknown, the investigators theorise that greater engagement in activities that preserve or increase cognitive reserve may thereby decrease dementia risk.

Recent evidence indicates there is a higher prevalence of sleep disturbances among older adults than among other age groups. This could be attributed to a variety of factors including anxiety about the COVID pandemic or warmer nights as a consequence of climate change.

“Older adults are losing sleep over a wide variety of concerns. More research is needed to better understand its causes and manifestations and limit the long-term consequences,” added Dr Wong. “Our findings highlight the importance of considering sleep disturbance history when assessing the dementia risk profile for older adults. Future research is needed to examine other sleep disturbance measures using a national longitudinal sample, whether these sleep-dementia findings hold true for specific dementia subtypes, and how certain sociodemographic characteristics may interact with sleep disturbances to influence dementia risk.”

Source: Elsevier

Categories : Ageing Diet and NutritionTags :

Vitamin D Supplements may Ward off Dementia

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Vitamin D pills
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Taking vitamin D supplements may help ward off dementia, according to a new, large-scale study published in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring.

Canadian and UK researchers explored the relationship between vitamin D supplementation and dementia in more than 12 388 participants of the US National Alzheimer’s Coordinating Center, who had a mean age of 71 and were dementia-free when they signed up.

The team found that taking vitamin D was associated with living dementia-free for longer, and they also found 40% fewer dementia diagnoses in the group who took supplements.

Of the group, 2696 participants progressed to dementia over ten years; amongst them, 2017 (75%) had no exposure to vitamin D throughout all visits prior to dementia diagnosis, and 679 (25%) had baseline exposure.

Professor Zahinoor Ismail, of the University of Calgary and University of Exeter, who led the research, said: “We know that vitamin D has some effects in the brain that could have implications for reducing dementia, however so far, research has yielded conflicting results. Our findings give key insights into groups who might be specifically targeted for vitamin D supplementation. Overall, we found evidence to suggest that earlier supplementation might be particularly beneficial, before the onset of cognitive decline.”

While Vitamin D was effective in all groups, the team found that effects were significantly greater in females, compared to males. Similarly, effects were greater in people with normal cognition, compared to those who reported signs of mild cognitive impairment – changes to cognition which have been linked to a higher risk of dementia.

The effects of vitamin D were also significantly greater in people who did not carry the APOEe4 gene, known to present a higher risk for Alzheimer’s dementia, compared to non-carriers. The authors suggest that people who carry the APOEe4 gene absorb vitamin D better from their intestine, which might reduce the vitamin D supplementation effect. However, no blood levels were drawn to test this hypothesis.

Previous research has found that low levels of vitamin D are linked to higher dementia risk. Vitamin D is involved in the clearance of amyloid in the brain, the accumulation of which is one of the hallmarks of Alzheimer’s disease. Studies have also found that vitamin D may provide help to protect the brain against build-up of tau, another protein involved in the development of dementia.

Co-author Dr Byron Creese, at the University of Exeter, said: “Preventing dementia or even delaying its onset is vitally important given the growing numbers of people affected. The link with vitamin D in this study suggests that taking vitamin D supplements may be beneficial in preventing or delaying dementia, but we now need clinical trials to confirm whether this is really the case. The ongoing VitaMIND study at the University of Exeter is exploring this issue further by randomly assigning participants to either take vitamin D or placebo and examining changes in memory and thinking tests over time.”

Source: University of Exeter

Categories : Ageing Pain ManagementTags :

The Impacts of Persistent Pain in Older Adults

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In a study of 5589 US adults aged 65 years and older, persistent pain was common and was linked to meaningful declines in physical function and well-being over 7 years. Reporting in the Journal of the American Geriatrics Society, investigators found that 38.7% of participants reported persistent pain, and 27.8% reported intermittent pain. (“Persistent pain” was defined as being bothered by pain in the last month in two consecutive annual interviews and “intermittent” pain was defined as bothersome pain in one interview only.)  

More than one-third of participants described pain in five or more sites. Over the subsequent 7 years, participants with persistent pain were more likely to experience declines in physical function (64% persistent pain, 59% intermittent pain, 57% no bothersome pain) and well-being (48% persistent pain, 45% intermittent pain, 44% no bothersome pain), but were not more likely to experience cognitive decline (25% persistent pain, 24% intermittent pain, 23% no bothersome pain).

“The findings from this study point to the importance of access to effective treatment for persistent pain in older adults and the need for additional research in chronic pain to optimise quality of life,” said lead author Christine Ritchie, MD, MSPH, of Massachusetts General Hospital.

Source: Wiley