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Ageing fight revealed in new ‘muscle map’

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The first comprehensive cell atlas of ageing human muscle reveals the intricate genetic and cellular processes behind muscle deterioration and mechanisms to counteract it.

How muscle changes with ageing, and tries to fight its effects, is now better understood at the cellular and molecular level with the first comprehensive atlas of ageing muscles in humans.

Researchers from the Wellcome Sanger Institute and their collaborators at Sun Yat-sen University, China applied single-cell technologies and advanced imaging to analyse human skeletal muscle samples from 17 individuals across the adult lifespan. By comparing the results, they shed new light on the many complex processes underlying age-related muscle changes.

The atlas uncovers new cell populations that may explain why some muscle fibres age faster than others. It also identifies compensatory mechanisms the muscles employ to combat ageing.

The findings offer avenues for future therapies and interventions to improve muscle health and quality of life as we age.

This study is part of the international Human Cell Atlas initiative to map every cell type in the human body, to transform understanding of health and disease.

As we age, our muscles progressively weaken. This can affect our ability to perform everyday activities like standing up and walking. For some people, muscle loss worsens, leading to falls, immobility, a loss of autonomy and a condition called sarcopenia. The reasons why our muscles weaken over time have remained poorly understood.

In this new study, scientists from the Wellcome Sanger Institute and Sun Yat-sen University, China used both single-cell and single-nucleus sequencing techniques along with advanced imaging to analyse human muscle samples from 17 individuals aged 20 to 75.

The team discovered that genes controlling ribosomes, responsible for producing proteins, were less active in muscle stem cells from aged samples. This impairs the cells’ ability to repair and regenerate muscle fibres as we age. Further, non-muscle cell populations within these skeletal muscle samples produced more of a pro-inflammatory molecule called CCL2, attracting immune cells to the muscle and exacerbating age-related muscle deterioration.

Age-related loss of a specific fast-twitch muscle fibre subtype, key for explosive muscle performance, was also observed. However, they discovered for the first time several compensatory mechanisms from the muscles appearing to make up for the loss. These included a shift in slow-twitch muscle fibres to express genes characteristic of the lost fast-twitch subtype, and increased regeneration of remaining fast-twitch fibre subtypes.

The team also identified specialised nuclei populations within the muscle fibres that help rebuild the connections between nerves and muscles that decline with age. Knockout experiments in lab-grown human muscle cells by the team confirmed the importance of these nuclei in maintaining muscle function.

Veronika Kedlian, first author of the study from the Wellcome Sanger Institute, said: “Our unbiased, multifaceted approach to studying muscle ageing, combining different types of sequencing, imaging and investigation reveals previously unknown cellular mechanisms of ageing and highlights areas for further study.”

Professor Hongbo Zhang, senior author of the study from Sun Yat-sen University, Guangzhou, China, said: “In China, the UK and other countries, we have ageing populations, but our understanding of the ageing process itself is limited. We now have a detailed view into how muscles strive to maintain function for as long as possible, despite the effects of ageing.”

Dr Sarah Teichmann, senior author of the study from the Wellcome Sanger Institute, and co-founder of the Human Cell Atlas, said: “Through the Human Cell Atlas, we are learning about the body in unprecedented detail, from the earliest stages of human development through to old age.With these new insights into healthy skeletal muscle ageing, researchers all over the world can now explore ways to combat inflammation, boost muscle regeneration, preserve nerve connectivity, and more. Discoveries from research like this have huge potential for developing therapeutic strategies that promote healthier ageing for future generations.”

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Mole rat gene extends mouse lifespan

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A mole rat gene inserted into mice extended lifespan and improved health, findings that may point to new ways of supporting healthier ageing.

The gene increased production of a large form of hyaluronan, a naturally occurring gel-like substance between cells that helps tissue repair and cell-to-cell communication. Mice carrying the naked mole rat version of the gene showed an approximately 4.4 per cent increase in median lifespan, alongside multiple markers of healthier ageing.

Naked mole rats have become a focus of ageing research because they combine an exceptional lifespan with unusual resistance to many age-linked diseases, including cancer.

Researchers at the University of Rochester traced part of that resilience to hyaluronan. The molecule’s effects depend on its size: large forms are often linked to anti-inflammatory and tissue-protective behaviour, while smaller fragments can act as danger signals that increase inflammation.

Vera Gorbunova, professor of biology and medicine at the University of Rochester in the US, said: “Our study provides a proof of principle that unique longevity mechanisms that evolved in long-lived mammalian species can be exported to improve the lifespans of other mammals.”

The engineered mice were better protected against both spontaneous tumours and chemically induced skin cancer. They also showed reduced inflammation across tissues, a notable finding because persistent low-grade inflammation, sometimes called inflammaging, is widely seen as one of the central drivers of age-related decline.

The research also linked the large form of hyaluronan to age-related gut health. As animals age, the gut barrier can become leakier, allowing inflammatory triggers to pass into the bloodstream. The engineered mice showed protection against this deterioration.

Follow-up work found abundant high-molecular-mass hyaluronan across multiple species of subterranean mammals, often absent in closely related above-ground species, suggesting it may be part of a broader evolutionary toolkit for surviving long lives under harsh conditions.

The team said gene transfer is not the end goal. Gorbunova said: “It took us 10 years from the discovery of HMW-HA in the naked mole rat to showing that HMW-HA improves health in mice.”

“Our next goal is to transfer this benefit to humans.”

Two practical routes are being pursued: increasing production of the large form of hyaluronan, or slowing its breakdown. Andrei Seluanov, who co-leads the research, said: “We already have identified molecules that slow down hyaluronan degradation and are testing them in pre-clinical trials.”

One candidate identified through screening is delphinidin, a plant pigment found in various fruits and vegetables. In tests, it was found to increase levels of the large form of hyaluronan in cells and mouse tissues, reduce migration and invasion in multiple cancer cell lines, and suppress melanoma metastasis in mice.

However, the researchers acknowledged the approach has limits. A later study found that mice expressing the naked mole rat gene showed improvements in several late-life health measures but did not show protection from age-related hearing loss, suggesting some organs may be less reachable by this pathway than others.

The Rochester team said turning these findings into human therapies will likely depend on precision: maintaining the right molecular form of hyaluronan, targeting the right balance of production versus breakdown, and monitoring carefully for trade-offs as different tissues respond in different ways.

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AI can predict Alzheimer’s with almost 93% accuracy, researchers say

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Alzheimer’s AI can predict the disease with nearly 93 per cent accuracy using more than 800 brain scans, researchers say.

The system identified anatomical changes in the brain linked to the onset of the most common form of dementia, a condition that gradually damages memory and thinking.

The findings build on years of research suggesting AI could help spot early Alzheimer’s risk, predict disease and identify patients whose condition has not yet been diagnosed.

Benjamin Nephew, an assistant research professor at the Worcester Polytechnic Institute in Massachusetts, said: “Early diagnosis of Alzheimer’s disease can be difficult because symptoms can be mistaken for normal ageing.

“We found that machine-learning technologies, however, can analyse large amounts of data from scans to identify subtle changes and accurately predict Alzheimer’s disease and related cognitive states.”

The study used MRI scans, a type of detailed brain imaging, from 344 people aged 69 to 84.

The dataset included 281 scans showing normal mental function, 332 with mild cognitive impairment, an early stage of memory and thinking decline, and 202 with Alzheimer’s.

The scans covered 95 of the brain’s nearly 200 distinct regions and used an AI algorithm to predict patients’ health.

Being able to use AI to help diagnose Alzheimer’s earlier could give patients and doctors crucial time to prepare and potentially slow the progression of the disease.

The analysis showed that one of the top predictive factors was brain volume loss, or shrinkage, in the hippocampus, which helps form memories, the amygdala, which processes fear, and the entorhinal cortex, which helps provide a sense of time.

This pattern held across age and sex, with both men and women aged 69 to 76 showing volume loss in the right part of the hippocampus, suggesting it may be an important area for early diagnosis, the researchers noted.

However, the research also found that the way brain regions shrink differs by sex.

In females, volume loss occurred in the brain’s left middle temporal cortex, which is involved in language and visual perception. In males, it was mainly seen in the right entorhinal cortex

The researchers believe this could be linked to changes in sex hormones, including the loss of oestrogen in women and testosterone in men.

These conclusions could help improve methods of diagnosis and treatment going forward, Nephew said.

More than 7.2m Americans are living with Alzheimer’s, according to the Alzheimer’s Association.

More research is being done to reveal other impacting factors.

Nephew said: “The critical challenge in this research is to build a generalisable machine-learning model that captures the difference between healthy brains and brains from people with mild cognitive impairment or Alzheimer’s disease.”

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Vision implant firm raises US$230m

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A vision implant firm has raised US$230m as it seeks approval in Europe and the US for a device that restored sight in a small clinical trial.

The Alameda, California-based startup said the funding would support commercialisation of its Prima device.

It said an upcoming launch is planned in Europe and that it would become the first brain computer interface company to have a vision restoration device on the market.

A clinical trial in Europe found the small implant could work as artificial photoreceptors in the retina to restore functional central vision.

The implant is placed under the retina to replace the function of light-sensitive cells lost to disease. A special pair of glasses with an embedded camera and infrared projector sends light signals to the implant.

The study assessed the system in people with advanced dry age-related macular degeneration.

Of the 38 patients who received an implant, 32 were assessed at 12 months. Results showed the device led to a clinically meaningful improvement in visual acuity in 26 people.

The patients were able to read letters, numbers and words, according to the company.

Science Corporation said it has submitted a CE mark application to the European Union and applied to the US Food and Drug Administration for regulatory approval.

Darius Shahida, chief strategy officer, said: “Our imperative is to become the first BCI company to scale and achieve profitability.”

Founded in 2021, the company has now raised about US$490m in total. It said it is expanding its clinical trial programme to include other retinal diseases, such as Stargardt disease and retinitis pigmentosa.

The Series C round included existing investors Khosla Ventures, Lightspeed Venture Partners, Y Combinator, IQT and Quiet Capital.

Science Corporation said demand for the round exceeded its capital needs, with funds also earmarked for expanding research, manufacturing infrastructure and operations.

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