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RNA discovery provides insight into bone diseases

A new study has revealed that the Cpeb4 protein may have a role in regulating osteoclast differentiation, a finding that could lead to the development of new therapeutic drugs for osteoporosis and rheumatoid arthritis.
In today’s aging societies, diseases affecting the bones and joints are becoming increasingly common. For example, in Japan alone, over 12 million people suffer from osteoporosis, a condition that severely weakens bones and makes them fragile.
In order to find effective treatments for these disorders, understanding the cellular processes involved in the maintenance of bone and joint tissue is an essential first step.
Osteoclasts are a particularly important type of cell involved in bone maintenance. These cells absorb old or damaged bone and digest it, allowing the body to reuse important materials like calcium and giving way to new bones.
Various bone diseases arise when osteoclasts do not fulfill their role properly, and scientists have been investigating the mechanisms that regulate the proliferation and differentiation of precursor cells into osteoclasts.
Researchers from Tokyo University of Science (TUS), led by Professor Tadayoshi Hayata, revealed in 2020 that the cytoplasmic polyadenylation element-binding protein 4 (Cpeb4) protein is essential in osteoclast differentiation.
They also discovered that this protein, which regulates the stability and translation of messenger RNA (mRNA) molecules, transported into specific structures within the nucleus of the cell when osteoclast differentiation was induced.
However, just how this relocation occurs and what Cpeb4 exactly does within these nuclear structures still remains a mystery.
Now, in a new study, Hayata and Yasuhiro Arasaki from TUS tackled these knowledge gaps, seeking to gain a better understanding of how the “life cycle” of mRNA, i.e. mRNA metabolism, is involved.
Cpeb4 proteins
The researchers introduced strategic modifications into Cpeb4 proteins and performed a series of experiments in cell cultures, finding that the localisation of Cpbe4 in the abovementioned nuclear bodies occurred owing to its ability to bind to RNA molecules.
Afterwards, seeking to understand the role of Cpeb4 in the nucleus, the researchers demonstrated that Cpeb4 co-localized with certain mRNA splicing factors. These proteins are involved in the process of mRNA splicing, which is a key step in mRNA metabolism. Put simply, it enables a cell to produce diverse mature mRNA molecules (and eventually proteins) from a single gene.
Through RNA sequencing and gene analysis in Cpeb4-depleted cells, they found that Cpeb4 alters the expression of multiple genes associated with splicing events in freshly differentiated osteoclasts.
Through further experiments, the researchers revealed that Cpeb4 only altered the splicing patterns of Id2 mRNA, an important protein known to regulate osteoclast differentiation and development.
Overall, this study sheds important light on the mechanisms that regulate osteoclast differentiation.
“Through this research, we were able to identify important factors involved in regulating mRNA splicing during the osteoclast differentiation process and obtained new knowledge regarding the control of mRNA splicing during osteoclast differentiation,” commented Professor Hayata.
While the contribution of Cpeb4 is smaller than that of RANKL, a signaling factor that induces osteoclast differentiation, targeting Cpeb4 may have the advantage of reducing the side effects of existing drugs as too much inhibition of osteoclast differentiation with RANKL inhibitory antibodies would halt bone remodeling.
Importantly, the results contribute to a more detailed understanding of how bones are maintained.
“Although we used cultured mouse cells in our study, there are also research reports that show a correlation between variations in the CPEB4 gene and bone density in humans,” added Hayata.
“We hope that our findings will help clarify the relationship between these two in the near future.”
Most importantly, the findings of the present study may prove to be a crucial stepping stone for advancing diagnostic techniques and treatments for bone and joint diseases.
GWAS analysis has reported a correlation between single nucleotide polymorphisms in introns of the CPEB4 gene region and the estimated bone density. Therefore, it is possible that CPEB4 expression and activity can be used as diagnostic criteria.
However, the researchers note that it is unclear whether Cpeb4 actually regulates bone metabolism in vivo. Therefore, clarification of the molecular basis of Cpeb4 in bone metabolism in mice would help to establish a therapeutic approach. Additionally, recent studies have reported that Cpeb4 is expressed in various cancer cells and contributes to cancer cell survival. In cancer, Cpeb4 contributes to mRNA stability, although splicing regulation may exist.
Hayata concluded: “The discovery of part of the mechanisms by which Cpeb4 controls osteoclast differentiation could lead to the elucidation of pathologies, including osteoporosis and rheumatoid arthritis, and ultimately become the foundation for the development of new therapeutic drugs.”
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Agetech investment & innovation round-up

Long-term gut health and female finance, London likes longevity
New York innovator Salvo Health has secured $8.5m in Series A round as it looks to develop new, long-term, gut-health treatments.
The funding round was led by ManchesterStory, City Light Capital and Threshold Ventures, with additional support from The Artemis Fund, Owl Capital, Impact X Capital Partners, Torch Capital and Felicis Ventures.
Eric Collins, co-founder and general partner of Impact X Capital Partners, a UK-based venture capital firm, said: “The key with Salvo is patient-centred care.
“It’s critical to expand access to food as medicine and behavioural health to improve outcomes and lower, long-term health care costs.
“Salvo does exactly that and has shown 76 per cent of patients report improved symptoms, with five accepted abstracts on outcomes, and a 79 per cent drop in GI-related ER utilisation for its patients.
“We can have better care at lower costs with innovation, in the US, and ultimately in the UK and Europe as well.”
The raise brings Salvo’s total equity funding to US$21.6m. Roughly 60m Americans experience chronic gastrointestinal conditions each year.
Salvo Health is positioning itself in the space between overburdened clinics and patients’ everyday lives.
Female longevity in focus
Xella Health – a women’s precision platform focused on fertility, ageing, and body changes – has raised over US$3.7m in pre-seed funding.
The funds will support product finalisation, partnerships, and a Spring 2026 launch, focused on sex-specific longevity and preventive care.
The round was led by Precursor Ventures, with participation from Capital F, Ulu Ventures, and other funds, as well as, strategic angel investors across healthcare, diagnostics, and consumer technology.
Xella is aiming to propel women’s health beyond symptom-based care and fragmented testing to deliver ‘integrated biological insight, clarity, and foresight’.
The company combines advanced diagnostics, longitudinal data, and personalised clinician-led guidance to help women understand what’s happening in their bodies today – and what lies ahead – across fertility, chronic conditions, hormonal health, early cancer detection, and preventative care.
“Our mission is to give women the answers and care they have always deserved,” said Kelly Lacob, co-founder & CEO of Xella.
“Xella is building the infrastructure to decode female biology – getting to the root cause of conditions that uniquely, differently or disproportionately affect women, many of which suffer from an unacceptably poor standard of care today.”
“Xella is rethinking women’s health from the ground up – starting with the insight women need to make sense of their own biology over time,” said Ashtan Jordan, principal at Precursor Ventures.
Age well in London
Two London boroughs have launched their own initiatives aimed at supporting their ageing resident populations.
Basildon Council has approved a new Ageing Population Strategy to support older residents live healthy, independent and connected lives.
The number of residents aged 65 and over in Basildon is projected to rise steadily over the next decade, reflecting national longevity trends.
The council says its ‘taking a proactive, preventative approach to ensure Basildon remains an inclusive, accessible and sustainable place for residents of all ages’.
The strategy emphasises strong partnership working with health services, voluntary and community organisations, local businesses and residents.
Key commitments include:
- Supporting people to remain independent in their own homes for longer,
- Promoting age-friendly design in town centres and public spaces,
- Strengthening dementia-friendly communities,
- Expanding opportunities for volunteering and employment, and
- Continuing investment in activity centres and community-led initiatives that reduce loneliness.
Cllr Melissa McGeorge, cabinet member for ageing population & health, said: “Our ambition is clear: to make Basildon a place where people can age well, feel valued, and continue to thrive at every stage of later life.
The ‘Life Curve’
Meanwhile the London Borough of Richmond has launched a new self-assessment tool developed by ADL Research and Newcastle University to help boost longevity.
The ‘Life Curve’ tool is designed to support healthy ageing with personalised advice and practical steps on how to stay active and independent.
Councillor Allen, lead member for adult social care, said: “Getting older doesn’t have to mean we stop being independent and there are small steps we can take to help reduce how getting older limits our lives.
“We have tools and services available in the borough to support residents to take these small daily steps to maintain their health and reduce the risk of conditions like heart disease, cancer and dementia.
“A new tool accessible right from your phone or any other online device is ‘Independent Richmond’, which helps you understand where you are on The Life Curve to help stay on track with healthy habits, keeping active and stay independent for longer.”
News
Bryan Johnson launches US$1m longevity programme

Bryan Johnson has launched a US$1m-a-year longevity programme with just three places, offering access to the exact protocol he has followed for five years.
The programme, called “Immortals”, is offered by the former fintech entrepreneur, now a prominent and often controversial figure in longevity.
Johnson’s unconventional methods have included Botox injections in his genitals (Botox relaxes muscles) and transfusions of blood from his teenage son.
There is no evidence these will help him outlive others.
The “Immortals” package includes a dedicated concierge team, 24/7 access to the BryanAI health coach, extensive testing, continuous tracking of millions of biological data points and what Johnson calls the “best skin and hair protocols.
A lower-cost supported tier is available at US$60,000 per year.
Rivals also target the ultra-wealthy: Biograph’s premium membership costs US$15,000 per year, while Fountain Life’s “ultimate longevity programme” is priced at US$21,500 annually.
Despite the higher price, Johnson’s offer is built on exclusivity, with only three spots available.
News
Cognition and Cera expand Alzheimer’s clinical trials access

Cognition Health and Cera have partnered to expand access to Alzheimer’s clinical trials across the UK.
The collaboration links Re:Cognition Health’s specialist brain health clinics and trial expertise with Cera’s 2.5 million monthly home care visits, creating new pathways to identify and support people earlier in their health journey.
By connecting home care with specialist research centres, the partners aim to offer more people the chance to join studies, giving access to advanced assessment and emerging treatments while contributing to future therapies.
Dr Ben Maruthappu MBE, chief executive and founder of Cera, said: “Many older adults are currently ‘invisible’ to the clinical trials research system because they cannot access traditional clinic-centric recruitment.
“By enabling responsible, consented identification and screening within the home, we can bridge the gap between the community and the clinic.
“We are offering the older generation a seat at the table of global drug discovery, ensuring that the path to a cure starts where they are most comfortable—in their own daily lives.”
Re:Cognition Health has contributed to the development of lecanemab (Leqembi) and donanemab (Kisunla) through international trials, introducing disease-modifying approaches that are reshaping early intervention in Alzheimer’s care.
Older adults remain under-represented in research. NIHR data indicate only about 15 per cent of trial participants are 75 or older, despite high multimorbidity in this group. Dementia trial recruitment in the UK also lags other disease areas.
Through this collaboration, individuals who have not yet accessed specialist memory services can be referred earlier for assessment and potential study participation, with access to new-generation therapies where appropriate.
Cera’s technology-enabled home healthcare model, with daily patient contact and consented data capture, allows timely referral of potential participants from familiar settings to Re:Cognition Health clinics.
Together, the organisations will support earlier and more equitable participation by leveraging Cera’s scale and real-time insights. Carers and nurses deliver visits roughly every second on average, enabling early identification of those who may benefit from memory assessment.
Dr Emer MacSweeney, chief executive and founder of Re:Cognition Health, said: “With one in three people expected to develop dementia in their lifetime, it is essential that we create more inclusive and accessible routes into research.
“This collaboration enables us to extend our reach beyond traditional clinic settings and ensure that people who may benefit from early assessment and research participation are supported to do so.
“Clinical trials offer individuals access to the most advanced diagnostics and emerging treatments, alongside expert medical oversight.
“By identifying people earlier and guiding them through every stage of their journey, we can help improve participants’ experience and potential outcomes, while accelerating the development of the next generation of Alzheimer’s therapies.”
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