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Synapse discovery paves way for Alzheimer’s and MS treatments



A new US study has for the first time revealed the function of a little-understood junction between cells in the brain that could have important treatment implications for conditions ranging from multiple sclerosis (MS) to Alzheimer’s disease.

The research is published in the journal Nature Neuroscience.

In the study, neuroscientists focused on the synapse connecting neurons to a non-neuronal cell, known as oligodendrocyte precursor cells, or OPCs.

OPCs can differentiate into oligodendrocytes, which produce a sheath around nerves called myelin.

This protective sheath covers each nerve cell’s axon — the threadlike portion of a cell that transmits electrical signals between cells.

The researchers discovered that these synapses play a pivotal role in producing that myelin.

Kelly Monk, Ph.D. is professor and co-director of the Vollum Institute at Oregon Health and Science University (HSU).

The researcher said: “This is the first investigation of these synapses in live tissue.

“This gives an understanding of the basic, fundamental properties of how these cells work in normal development.

“In the future, we might look at how they function differently in the context of MS patients.”

The fact that these synapses exist at all was the subject of a landmark discovery by OHSU researchers at the Vollum that was published in the journal Nature in May 2000.

Until that point, synapses in the brain had been known only to carry neurotransmitters between neurons, so the discovery of a synapse between neurons and OPCs came as a revelation to researchers.

Monk said: “After two decades, we still didn’t know what these synapses do.”

The researchers tackled the problem by using single-cell imaging of live tissue in zebrafish, whose transparent bodies enable researchers to see the inner workings of their central nervous system in real time.

Using powerful new tools in imaging, pharmacology and gene editing, scientists were able to use neuron-OPC synapses to predict the timing and location of the formation of myelin.

The findings are likely the tip of the iceberg in terms of understanding the importance of these synapses, according lead author Jiaxing Li, Ph.D., a postdoctoral fellow in Monk’s lab.

Oligodendrocyte precursor cells comprise about 5 per cent of all cells in the brain — meaning the synapses they form with neurons could be relevant to many disease conditions, including the formation of cancerous tumours.

Li noted that previous studies have suggested a role for OPCs in a range of neurodegenerative conditions, including demyelinating disorders such as MS, neurodegenerative diseases such as Alzheimer’s and even psychiatric disorders such as schizophrenia.

By demonstrating the basic function of the synapse between neurons and OPCs, the study may lead to new methods of regulating OPC function to alter disease progression, Li said.

For example, the synapses could be the key to promoting remyelination in conditions such MS, where myelin has been degraded.

In MS, this degradation can slow or even block electric signals required for people to see, move their muscles, feel sensations and think.

Li said: “There may be a way to intervene so that you can increase the myelin sheath.”

Monk believes that the discovery may be most immediately relevant to cancer.

The researcher said: “In glioma, these synapses are hijacked to drive tumour progression.

“It may be possible to modulate the synaptic input involved in tumour formation, while still allowing for normal synaptic signalling.”

Even though these precursor cells comprise roughly 5 per cent of all human brain cells, only a fraction go on to form oligodendrocytes.

Monk said|: “It’s becoming pretty clear that these OPCs have other functions aside from forming oligodendrocytes.

“From an evolutionary perspective, it doesn’t make sense to have so many of these precursor cells in your brain if they’re not doing something.”

Their synaptic connection to neurons therefore likely plays a fundamental role in the brain, and is worthy of future exploration, the researcher added.


Tai chi outperforms conventional exercise for seniors



New findings from 12 studies involving 2,901 participants have demonstrated that tai chi outperforms conventional exercise in improving mobility and balance in seniors.

While tai chi is understood to be beneficial for functional mobility and balance in older adults, such benefits are not well understood due to large variance in research study protocols and observations.

This new review and analysis has now shown that tai chi can induce greater improvement in functional mobility and balance in relatively healthy older adults compared to conventional exercise.

The findings showed the following performance results:

  • The time to complete 50-foot walking was 1.84 seconds faster. 
  • The time to maintain a one-leg stance was 6 seconds longer when eyes were open and 1.65 seconds longer when eyes were closed. 
  • Individuals improved their timed-up-and-go test performance by 0.18 points, indicating quicker standing, walking, and sitting.
  • Individuals taking the functional reach test showed significant improvement with a standardised mean difference of 0.7, suggesting a noteworthy positive impact on the ability to reach and perform daily activities.

Secondary analyses revealed that the use of tai chi with relatively short duration of less than 20 weeks, low total time of less than 24 total hours, and/or focusing on the Yang-style of this ancient form of Chinese martial arts were particularly beneficial for functional mobility and balance as compared to conventional exercise.

“This systematic literature review and meta-analysis are exciting because they provide strong evidence that tai chi is a more efficient strategy to improve functional mobility and balance in relatively healthy older adults, as compared to conventional exercise,” said Brad Manor, Ph.D., director of the Mobility and Falls Program at Hebrew SeniorLife’s Hinda and Arthur Marcus Institute for Aging Research, and associate professor of medicine, Harvard Medical School and Beth Israel Deaconess Medical Center.

“This research suggests that tai chi should be carefully considered in future studies and routines of rehabilitative programs for balance and mobility in older adults,” said Bao Dapeng, professor at Beijing Sport University.

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New standards for biomarkers of ageing



A paper has put forward a new framework for standardising the development and validation of biomarkers of ageing to better predict longevity and quality of life.

Led by Harvard researchers, the team has zeroed in on biomarkers of ageing using omic data from population-based studies. 

The team included ageing and longevity expert Alex Zhavoronkov, PhD, founder and CEO of AI-driven drug discovery company Insilico Medicine, and the findings appeared in Nature Medicine

Ageing is associated with a number of biological changes including increased molecular and cellular damage, however, researchers do not yet have a standardised means to evaluate and validate biomarkers related to ageing. 

In order to create those standards as well as actionable clinical tools, the team analysed population-based cohort studies built on omic data (data related to biological molecules which can include proteomics, transcriptomics, genomics, and epigenomics) of blood-based biomarkers of ageing. The researchers then compared the predictive strength of different biomarkers, including study design and data collection approaches, and looked at how these biomarkers presented in different populations. 

In order to better assess the impact of ageing using biomarkers, the researchers found that clinicians needed to expand their focus to consider not only mortality as an outcome, but also how biomarkers of aging are associated with numerous other health outcomes, including functional decline, frailty, chronic disease, and disability. They also call for the standardisation of omic data to improve reliability. 

“Omics and biomarkers harmonisation efforts, such as the Biolearn project, are instrumental in validation of biomarkers of aging” said co-first author Mahdi Moqri, PhD, of the Division of Genetics. 

Biolearn is an open-source project for biomarkers of aging and is helping to harmonise existing ageing biomarkers, unify public datasets, and provide computational methodologies.

The team also emphasised the importance of continued collaborations among research groups on “large-scale, longitudinal studies that can track long-term physiological changes and responses to therapeutics in diverse populations”, and that further work is required to understand how implementation of biomarker evaluation in clinical trials might improve patient quality of life and survival.

“If we hope to have clinical trials for interventions that extend healthy lifespan in humans, we need reliable, validated biomarkers of ageing,” said co-first author Jesse Poganik, PhD, of the Division of Genetics. 

“We hope that our framework will help prioritise the most promising biomarkers and provide health care providers with clinically valuable and actionable tools.”

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Healthy aging research to receive $115 million



Global non-profit Hevolution Foundation has announced $115 million in funding that makes up 49 new awards under its Geroscience Research Opportunities (HF-GRO) programme.  

As part of Hevolution’s mission to catalyse the healthspan scientific ecosystem and drive transformative breakthroughs in healthy aging, HF-GRO is funding promising pre-clinical research in aging biology and geroscience. 

Through this first wave of HF-GRO awards, Hevolution will invest up to $115 million in this first cohort of 49 selected projects over the next five years. Its second call for proposals under HF-GRO will be announced later this year, offering an additional $115 million to address the significant funding gaps in aging research.  

Dr. Felipe Sierra, Hevolution’s Chief Scientific Officer stated: “These 49 important research projects represent a significant step forward in deepening our understanding of healthy aging. Hevolution’s prime objective is to mobilise greater investment around uncovering the foundational mechanisms behind biological aging. 

“We are steadfast in our belief that by examining the root causes of aging, rather than solely focusing on its associated diseases, we can usher in a brighter future for humanity.” 

HF-GRO awardees include researchers at prestigious institutions across the United States, Canada, and Europe, including the U.S. National Institute on Aging, Brigham and Women’s Hospital, the Buck Institute, the Mayo Clinic, New York University, and the University of California San Francisco, among many others. 

The American Federation for Aging Research is providing programmatic support for the HF-GRO program, with grantees selected through a rigorous two-stage peer-review process involving 100 experts in aging biology and geroscience. 

Dr Berenice Benayoun, an HF-GRO grant recipient at the University of Southern California, stated: “I am extremely honored and excited that Hevolution selected our project for funding. This is a project close to my heart, which aims at understanding why and how the female and male innate immune aging differs. 

“This funding will support us as we start laying the foundation for a lasting improvement of women’s health throughout aging.” 

To date, Hevolution has committed approximately $250 million to transform the healthy aging sector, including the $40 million for specialised research and development in healthspan science recently announced at Hevolution’s Global Healthspan Summit. 

Hevolution is ramping up its investments to enable healthier aging for all and is now the second largest funder of aging biology research worldwide.  

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