Category: Ageing

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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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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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

Categories : Ageing COVIDTags :

COVID Deadlier than Bacterial or Viral Pneumonia for Older ICU Patients

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For older patients in intensive care units (ICUs), COVID is more severe than bacterial or viral pneumonia, suggests new research published in the Journal of the American Geriatrics Society.

Among 11 525 patients aged 70 years and older who were admitted to Dutch ICUs, ICU-mortality and hospital-mortality rates of patients admitted with COVID were 39.7% and 47.6%, respectively. These rates were higher than the mortality of patients admitted because of pneumonia from causes other than COVID. (ICU- and hospital-mortality rates of patients admitted with bacterial pneumonia were 19.1% and 28.8%, respectively, and with viral pneumonia were 22.7% and 31.8%, respectively). Differences persisted after adjusting for several clinical characteristics and intensive care unit occupancy rate.

“In ICU-patients aged 70 years and older, COVID is more severe – with approximately double mortality rates – compared with bacterial or viral pneumonia. Nevertheless, more than half of these older patients admitted to Dutch ICUs with COVID survived the hospital,” said corresponding author Lenneke E. M. Haas, MD, PhD, of Diakonessenhuis, in the Netherlands. “Our findings provide important additional data to include in informed goals-of-care discussions.”

Source: Wiley

Categories : Ageing Injury & TraumaTags :

Mandatory Cognitive Screening for Older Drivers Reduces Car Crashes

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New research published in the Journal of the American Geriatrics Society reports that motor vehicle collisions decreased after Japan implemented a mandatory cognitive screening test for older drivers when they renewed their drivers’ licences. For older pedestrians and cyclists, however, their number of collisions and injuries increased.

For the study, investigators analysed police-reported data on the number of collisions for drivers and injuries for pedestrians and cyclists among people aged 70 years or older in Japan from July 2012 to December 2019. As of March 2017, drivers aged 75 years or older who screen positive are required to see a physician before license renewal. If diagnosed with dementia, their licenses may be suspended or revoked.

From 2012 to 2019, there were 602 885 collisions for drivers and 196 889 injuries for pedestrians and cyclists among people aged 70 years or older. After the 2017 policy, collisions decreased among male drivers, and injuries increased among some age subgroups in both sexes. Cumulative estimated changes in the numbers of collisions and injuries from March 2017 to December 2019 were -3670 and 959, respectively.

“Safety measures need to be strengthened for older cyclists and pedestrians. We should also provide older people with necessary care to prepare for driving cessation and safe, alternative transport means,” said corresponding author Haruhiko Inada, PhD, a post-doctoral fellow at the Johns Hopkins Bloomberg School of Public Health.

Source: Wiley

Categories : AgeingTags :

Can Revitalising Old Blood Stem Cells Slow Ageing?

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Studies over the past several years have shown that infusions of young blood seem to produce a rejuvenating effect when infused into older bodies. Ageing hearts beat stronger, muscles become stronger, and thinking becomes sharper.

While some scientists have considered trying to replicate this effect with a pill, others have focused on rejuvenating the haematopoietic stem cells that actually make the blood – something which may be possible, based on recent findings from a study published in Nature Cell Biology.

“An ageing blood system, because it’s a vector for a lot of proteins, cytokines, and cells, has a lot of bad consequences for the organism,” says Emmanuelle Passegué, PhD, director of the Columbia Stem Cell Initiative, who’s been studying how blood changes with age. “A 70-year-old with a 40-year-old blood system could have a longer healthspan, if not a longer lifespan.”

Passegué, with her graduate student Carl Mitchell, found that an anti-inflammatory drug, already approved for use in rheumatoid arthritis, can turn back time in mice and reverse some of the effects of age on the hematopoietic system.

“These results indicate that such strategies hold promise for maintaining healthier blood production in the elderly,” Mitchell says.

Returning blood stem cells to a younger state

The researchers only identified the drug after a investigation of stem cells for blood and the niches where they reside in the centre of the bones.

All blood cells in the body are created by a small number of stem cells that reside in bone marrow. Over time, these haematopoietic stem cells start to change, producing fewer red blood cells (leading to anaemia) and fewer immune cells (which raises the risk of infection and impedes vaccination efforts), and they have trouble maintaining the integrity of their genomes (which can lead to blood cancers).

In a 2021 Journal of Experimental Medicine paper, Passegué and her team first tried to rejuvenate old haematopoietic stem cells in mice, with exercise or a calorie-restricted diet, both generally thought to slow the ageing process. Both failed, as did transplanting old stem cells into young bone marrow. Even young blood had no effect on rejuvenating old blood stem cells.

Mitchell and Passegué then took a closer look at the stem cells’ environment, the bone marrow. “Blood stem cells live in a niche; we thought what happens in this specialised local environment could be a big part of the problem,” Mitchell says.

With techniques developed in the Passegué lab that enable detailed investigation of the bone marrow milieu, the researchers found that the ageing niche is deteriorating and overwhelmed with inflammation, leading to dysfunction in the blood stem cells.

One inflammatory signal released from the damaged bone marrow niche, IL-1B, was critical in driving these ageing features, and blocking it with the drug, anakinra, remarkably returned the blood stem cells to a younger, healthier state.

Even more youthful effects on both the niche and the blood system occurred when IL-1B was prevented from exerting its inflammatory effects throughout the animal’s life.

The researchers are now trying to learn if the same processes are active in humans and if rejuvenating the stem cell niche earlier in life, in middle age, would be a more effective strategy.

Meanwhile, “treating elderly patients with anti-inflammatory drugs blocking IL-1B function should help with maintaining healthier blood production,” Passegué says, and she hopes the finding will lead to clinical testing.

“We know that bone tissue begins to degrade when people are in their 50s. What happens in middle age? Why does the niche fail first?” Passegué says. “Only by having a deep molecular understanding will it be possible to identify approaches that can truly delay ageing.”

Many societies have added more than 30 years to life expectancy in the past century. “Now it is imperative to conduct the science to determine how to create health and well-being across the full length of those lives,” says Linda Fried, MD, MPH, dean of the Mailman School of Public Health at Columbia University and director of the Butler Columbia Aging Center. “This must include research to understand the mechanisms of normal aging and how to fully develop the huge opportunities to create healthy longevity for all.”

Source: Columbia University Irving Medical Center

Categories : Ageing GenderTags :

Sex and Age Influence the Circadian Rhythm

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In a new study published in the journal Science, researchers exploring circadian molecular rhythms were able to uncover the organisation of gene expression rhythms in particular human tissues, and found that sex and age are involved, with females having a more regular pattern of rhythms.

In model organisms, analysing molecular rhythms is usually done using time-stamped measurements, but such data are not readily available in humans. To work around this, the researchers used existing measurements from a large cohort of post-mortem donors, combined with a novel computer algorithm that was designed to assign internal clock times to nearly one thousand donors.

“Interestingly, the data-science algorithm we developed turned out to resemble models from magnetic systems, which are well studied in statistical physics,” says study leader Felix Naef at Ecole Polytechnique Fédérale de Lausanne. Using this innovative approach, the researchers obtained the first comprehensive and accurate whole-organism view of 24-hour gene expression rhythms in 46 human tissues.

While the core clock machinery properties are conserved across the body and do not change significantly with sex and age, their analysis also revealed extensive programs of gene expression rhythms across major compartments of metabolism, stress response pathways and immune function, and these programs peaked twice a day.

In fact, the emerging whole-body organisation of circadian timing shows that rhythmic gene expression occurs as morning and evening waves, with the timing in the adrenal gland peaking first, while brain regions displayed much lower rhythmicity compared to metabolic tissues.

Dividing the donors by sex and age revealed a previously unknown richness of sex- and age- specific gene expression rhythms spread across biological functions. Strikingly, gene expression rhythms were sex-dimorphic (different in males and females) and more sustained in females, while rhythmic programs were generally reduced with age across the body.

Sex-dimorphic rhythms were particularly noticeable in the liver’s “xenobiotic detoxification,” the process by which liver breaks down harmful substances. Additionally, the study found that with age, the rhythm of gene expression decreases in the heart’s arteries, which may explain why older people are more susceptible to heart disease. This information could be useful in the field of “chronopharmacology,” which is the study of how a person’s internal clock affects the effectiveness and side effects of medication.

This study provides new insights into the complex interplay between our body clock, sex, and age. By understanding these rhythms, we might find new ways of diagnosing and treating pathologies such as sleep disorders and metabolic diseases.

Source: Ecole Polytechnique Fédérale de Lausanne