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Model of human synovium could accelerate treatments for arthritis

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Researchers have developed a new ‘organ-on-a-chip’ model of the human synovium, a membrane-like tissue that lines the joints.

The model, published in the journal Biomedical Materials, could help scientists to better understand the mechanisms of arthritis and to develop new treatments for the group of debilitating diseases.

Across the globe, more than 350 million people live with a form of arthritis, which affects the joints and can cause pain, stiffness, and swelling.

There is currently no cure and the search for new therapeutics is limited by a lack of accurate models.

The new synovium-on-a-chip model, developed at Queen Mary University of London, is a three-dimensional microfluidic device that contains human synovial cells and blood vessel cells.

The device is subjected to mechanical loading, which mimics the forces applied to the synovium during joint movement.

The model was able to mimic the behaviour of native human synovium, producing key synovial fluid components and responding to inflammation.

This suggests that the new platform has immense potential to help researchers understand disease mechanisms and identify and test new therapies for arthritic diseases.

Synovium-on-a-chip

“Our model is the first human, vascularised, synovium-on-a-chip model with applied mechanical loading and successfully replicates a number of key features of native synovium biology,” said Dr Timothy Hopkins, joint lead author of the study.

“The model was developed upon a commercially available platform (Emulate Inc.), that allows for widespread adoption without the need for specialist knowledge of chip fabrication.

“The vascularised synovium-on-a-chip can act as a foundational model for academic research, with which fundamental questions can be addressed, and complexity (further cell and tissue types) can be added.

“In addition, we envisage that our model could eventually form part of the drug discovery pipeline in an industrial setting. Some of these conversations have already commenced.”

The researchers are currently using the model to study the disease mechanisms of arthritis and to develop stratified and personalised organ-on-a-chip models of human synovium and associated tissues.

“We believe that our synovium-on-a-chip model, and related models of human joints currently under development in our lab, have the potential to transform pre-clinical testing, streamlining delivery of new therapeutics for treatment of arthritis,” Martin Knight, Professor of Mechanobiology, said.

“We are excited to share this model with the scientific community and to work with industry partners to bring new treatments to patients as quickly as possible.”

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OptimallyMe launches UK’s first epigenetic DNA age test

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Health tech brand, OptimallyMe, has launched the UK’s first epigenetic DNAm analytic test, which aims to optimise longevity and reduce ageing.

OptimallyMe’s exclusive ‘DNA Methylation and Epigenetic Age Test’ is a brand-new analytics tool, that provides comprehensive insights into genetic makeup, health, and the ageing process. 

While many people invest serious time and money in the biohacking arena, until the launch of this new test with its accompanying personalised health tech dashboard, there has been no real way to actually measure quantifiably if these investments work.  

The test analyses DNA methylation patterns with scientific techniques to uncover epigenetic age based on the Horvaths Clock methodology GrimAge2. 

Unlike the genetic DNA methylation tests that are on the market, this test focuses on ‘epigenetic DNA methylation’ and identifies completely different biomarkers, which no other DNA test measures.

These biomarkers (risk factors) are associated with specific organ/system ageing and include:

  • Metabolic ageing (with HbA1c as a risk factor)
  • Heart Ageing (CRP)
  • Lung Ageing (PACKYRS)
  • Immune Ageing (Leptin)
  • Vascular Ageing (PAI-1)
  • Cellular Ageing (ADM)
  • ECM Ageing (TIMP-1)
  • Kidney Ageing (Cystatin C)
  • Brain Ageing (B2M)
  • and Muscle Ageing (GDF).

Genetic DNA methylation analyses the methylation status of DNA to identify genetic patterns that may predispose individuals to certain diseases or conditions, typically centring on specific genes to assess hereditary risks.

OptimallyMe

However, OptimallyMe’s test examines changes in DNA methylation caused by environmental factors, lifestyle, and other non-genetic influences. These modifications are not part of the DNA sequence itself but do impact gene expression and function.

This approach helps understand how external factors influence gene expression.

Analysis of epigenetic mDNA is aimed at determining the ageing process, comparing biological age with chronological age. Crucially, biological age is modifiable; it can be influenced.

Tracking biological age can illustrate changes over time and reveal the impact of diet, lifestyle modifications, and anti-ageing treatments on the rate of ageing. Biological age measurement (known as GrimAge) has been robustly associated with predicting future healthspan and lifespan.

Users will gain unique insights into their potential health risks and receive detailed personalised recommendations for lifestyle modifications.

This knowledge should help them make informed choices to optimise well-being, promote longevity and reverse biological age, and most importantly are able to monitor progress and effectiveness through repeat testing. It is recommended that the test is repeated six months after first use, to see if the various longevity practices and anti-aging products being used are actually working. 

Mina Stanisavljevic, OptimallyMe.

Mina Stanisavljevic, a specialist in Molecular Biology and Physiology, and product research and developer’ at OptimallyMe, explains: “By testing epigenetic mDNA, we obtain a biological age to contrast with chronological age. For example, if someone is 26 years old chronologically, their biological age might be 30. The aim is for biological age to be the same as, or even less than, chronological age. In cases where the biological age is greater – as in the given example – we can pinpoint which organ/system is ageing most and provide tailored recommendations on reducing the biological age back to the chronological level.

“This way, we help people stay younger and healthier for longer.  for instance, if a person’s kidney-related biomarker (risk factor), cystatin C, is increased, it indicates that kidneys are affecting ageing process. Therefore, we focus on strategies to optimise this biomarker (personalised recommendations with lifestyle, diet, supplementation implementations), thus potentially improving kidney health and reducing biological age.”

She continues: “Overall, at OptimallyMe our goal is to help individuals live healthier, longer lives.  Our innovative health dashboard has also been designed to pull in health data beyond testing, including data from smart wearable devices, a series of health questionnaires and even a skin health tool, holding all health data in one place for a holistic overview.”

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UK body calls for more ageing research backing

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The British Society for Research on Ageing (BSRA) is calling for more public backing in the UK for research to help people stay healthier for longer, as an alternative to charities that support research on diseases.

The greatest risk factor for disease is ageing, but we have very little charitable support for research into how to slow ageing, the organisation warns.

Many diseases such as cancers and heart disease tragically shorten lives far too early, or like Alzheimer’s and arthritis, destroy quality of life for patients and carers. There is understandably huge public charitable support for more research. However, the greatest risk factor for those diseases, and even infectious diseases like COVID, is ageing.

Yet in comparison there is currently very little support for research to understand how we can slow ageing to prevent disease. This approach may be more productive in the long term to fight disease. Furthermore, keeping people healthier for longer, or avoiding chronic diseases all together, would be the most favourable outcome.

The UK population is ageing fast, putting pressure on the NHS and the economy. Despite this pressing problem all around us, there is no accessible way for people to support research into ageing in the UK. The BSRA aims to change that.

With a very small budget and almost completely run by volunteers, the BSRA has successfully funded several small research projects but progress needs to be accelerated. More funding is needed because it takes years to see the effects of ageing, so studies are long. Also ageing affects individuals in different ways, meaning that large numbers of people must be studied to make firm conclusions.

Therefore, there is an urgency to get studies funded and the BSRA has decided to launch an ambitious fundraising campaign to boost research into ageing. Initially, the Society aims to fund a series of one year research projects at the Masters degree level at universities across the UK and with plans to raise much more in the future to support longer and more ambitious projects that will impact the lives of the general public.

Chair of the BSRA, Prof David Weinkove from Durham University, says “The time is now to really get behind research into the biology of ageing. We have fantastic researchers across the country, but they are held back by a lack of funding. Evidence-based research is needed to understand how we people can stay healthier for longer, and to then we must make that knowledge available to as many people as possible”.

Dr Jed Lye says “This is a great opportunity for the public to help, for corporations to contribute, or philanthropists wanting a large impact with a relatively small donation; every £20,000 we raise can fund an entire year of research into ageing and longevity, and gets a budding scientist their research qualification.”

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Wearable device could provide early warning of Alzheimer’s

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App for monitoring Parkinson’s disease gets FDA clearance

Monitoring daily activity patterns using a wrist-worn device may detect early warning signs of Alzheimer’s disease, according to a new study led by researchers at the Johns Hopkins Bloomberg School of Public Health.

The researchers analysed movement data from wristwatch-like devices called actigraphs worn by 82 cognitively healthy older adults who were participants in a long-running study of aging. Some of the participants had detectable brain amyloid

buildup as measured by PET scan. Buildup of the protein amyloid beta in the brain is a key feature of Alzheimer’s disease.

Using a sensitive statistical technique, the researchers found significant differences between this “amyloid-positive” group and “amyloid-negative” participants in mean activity in certain afternoon periods and differences in variability of activity across days in a broader range of time windows.

The new study was published online February 21 in the journal SLEEP.

“We need to replicate these findings in larger studies, but it is interesting that we’ve now seen a similar difference between amyloid-positive and amyloid-negative older adults in two independent studies,” says Adam Spira, PhD, professor in the Department of Mental Health at the Bloomberg School.

The new study’s results partly confirm findings from an earlier study in a smaller sample, also led by Spira, and suggest that actigraphs someday could be a tool to help detect incipient Alzheimer’s disease before significant cognitive impairment sets in. Data from the prior study came from participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies.

For their new study, Spira and colleagues investigated the potential of actigraph-based monitoring in 82 community-dwelling individuals whose average age was about 76. Each participant had a PET scan to measure brain amyloid and wore an actigraph 24 hours per day for one week. Using a sensitive statistical technique called FOSR (function-on-scalar regression), the researchers found that the 25 amyloid-positive participants, compared to the 57 amyloid-negative participants, had higher mean activity during the early afternoon, 1:00 to 3:30 p.m., and less day-to-day variability in activity from 1:30 to 4:00 p.m. and 7:30 to 10:30 p.m.

In more conservative analyses, some of these time windows with differences were no longer statistically significant. Nonetheless, the higher afternoon activity and lower afternoon variability echoed the investigators’ prior findings.

Alzheimer’s disease, the leading cause of dementia, is estimated to affect more than six million older adults in the U.S. The Alzheimer’s disease process is still not fully understood but is characterised by amyloid plaques and tangles in the brain, which typically begin to accumulate a decade or two before Alzheimer’s is diagnosed.

The only approved treatments that may slow the disease course are those that target amyloid beta and reduce the plaques. Many researchers believe that such treatments can be much more effective if given earlier in the disease course—ideally, years before dementia becomes evident.

Abnormal patterns of sleep and waking activity have been studied as potential early indicators of Alzheimer’s. Alzheimer’s patients typically have abnormal sleep-wake rhythms, and prior studies have found evidence that amyloid accumulation may disrupt sleep-wake rhythms relatively early in the disease process. There is also evidence that sleep loss promotes amyloid accumulation, suggesting a “vicious circle.”

Such findings hint at the possibility that older adults might someday, among other measures, wear wristwatch-like devices that would automatically track and analyse their sleep and waking activity. Individuals with anomalous activity patterns could then consult their physicians for more in-depth Alzheimer’s screening.

The individuals in the new study were participants in a long-running study, the Baltimore Longitudinal Study of Aging, which is conducted by the Intramural Research Program of the National Institute on Aging (NIA), part of the National Institutes of Health (NIH). Several members of the NIA team were co-authors of the study.

Standard, non-FOSR statistical methods did not detect any significant differences in activity or sleep patterns, suggesting the methods may be less sensitive to amyloid deposition.

In the earlier actigraphy study, the researchers, using FOSR-based analyses in a different sample of 59 participants, found increases in mean activity in afternoon hours and differences in variability, including lower variability in the afternoon, among amyloid-positive participants.

The scientists don’t know why amyloid buildup would trigger differences in activity patterns during these particular times of day. They note that there is a well-known phenomenon among individuals with Alzheimer’s disease called “sundowning,” in which agitation increases in the afternoon and early evening.

“It’s conceivable that the higher afternoon activity we observed is a signal of ‘preclinical sundowning,’” Spira says.

“At the same time, it’s important to note that these findings represent averages among a small sample of older people over a short period of time. We can’t predict whether an individual will develop amyloid plaques based on the timing of their activity. So, it would be premature for older people to be concerned because their fitness trackers say they are particularly active in the afternoon, for example.”

He and his colleagues plan to do larger studies of this kind. They also hope to do longer-term studies to see if daily activity-pattern changes are associated not only with brain amyloid but also with actual cognitive decline.

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