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World-leading study on human ageing launches next phase

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The world-leading Dunedin Study is set to launch its next stage, delving into an understudied but important period of life and time of change.

The Dunedin Multidisciplinary Health and Development Study is the most detailed study of human health and development in the world, following the lives of 1037 babies born in Queen Mary Maternity Hospital between 1 April 1972 and 31 March 1973.

Members have been assessed regularly throughout their lives, most recently at age 45.

Researchers are now preparing to begin the next stage of age 52 assessments on 8 April, 2024.

Research often focuses on childhood or old age, leaving a gap in information about people in the middle part of their lives and how their health is shaped by their early lives and will affect how they age.

By adding the new age-52 data to the information gathered from Study members in their 30s and 40s, researchers will be in a rare position to understand how people age.

“Midlife is an understudied period of time when it comes to understanding health and wellbeing,” says study director, Research Professor Moana Theodore.

“Not only is it a time of change – people’s children may be leaving home and their parents are getting older – but it’s also when significant health issues can arise.

“Chronic conditions emerge at earlier ages for some of our communities who have less access to services and experience inequities in health. The best way to study inequities is to identify lifecourse pathways that create them to inform programmes that address inequities now and for future generations.”

Professor Theodor adds: “Why that’s so important is because we have an ageing population. Some of our most pressing healthcare, social, and economic issues relate to how we best support and care for people as they age.”

The assessments will take about two years to complete and participants will undergo a range of physical tests including a dental examination, vision, hearing and respiratory tests, as well as answering many questions about their lives. They will also attend a brain MRI scan on a second day.

Professor Theodore says researchers ensure as many members can participate as possible, bringing them to Dunedin from all over the world. Incredibly, 94 per cent of all living members took part in the age 45 assessments, making it the highest follow-up rate for a study of this design and duration in the world.

This is what sets it apart from other longitudinal studies, she says.

“The study members come from all walks of life. Our high retention rate gives us the ability to look at the wide range of human experiences. The fact that we have this world-leading study right here in Aotearoa New Zealand is something that we should all be incredibly proud of. But it is only possible due to the generosity of each and every one of our study members and their families,” Professor Theodore commented.

“The study members are the true heroes of this study. They have given half a century of service to their country. In recognition of their contribution, they each anonymously received a Civic Award from the City of Dunedin in 2010, and a copy of the study’s 2016 Prime Minister’s Science Prize certificate. The study itself was also awarded the Rutherford Medal in 2022, the most prestigious national research award.”

The last time participants were seen was before the COVID-19 pandemic and the study is in a unique position to examine how people’s lives have changed since then. Researchers are also increasing their focus on how the environment impacts health. New technologies will look at members’ exposure to chemical toxins like pesticides, air pollution, and heavy metals.

Professor Theodore was named director in October 2023, after the untimely passing of former director Emeritus Distinguished Professor Richie Poulton.

Professor Theodore is only the third director in 51 years, and the first director who is Generation X, the same age as the study members.

“Like many New Zealand students and researchers, I have been fortunate to learn and train at the study. Richie was a long-time mentor of mine. He knew that the data that we collect would become more and more valuable and helpful over time – that the best years of the study were still to come.

“I work alongside a team of staff who will ensure we build upon the study’s legacy. A team that is absolutely committed to the Study and the Study members and working alongside internationally renowned researchers across such a broad range of multidisciplinary areas.”

One of those leading researchers is the study’s associate director Professor Terrie Moffitt. Professor Moffitt, who is based at Duke University in North Carolina, says the study has had a significant impact internationally.

“The study has from the outset aimed first to improve health in New Zealand,” she says. “But it is also well-regarded as a trusted source of health information overseas.”

Professor Moffitt says the measures used are the same quality used in clinics and its findings are published in top international medical journals.

“Most studies just stay on the surface, they send out postal questionnaires, or collect saliva through the post, or collect data over the internet. But each and every Dunedin Study member spends a whole day in person, at the unit, being assessed in depth.”

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ChatGPT shows promise as medication management tool

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Researchers have found that ChatGPT may hold promise as a tool to manage medication and polypharmacy—which could be particularly helpful in the care of older adults.

Polypharmacy, or the concurrent use of five or more medications, is common in older adults and increases the risk of adverse drug interactions. While de-prescribing unnecessary drugs can combat this risk, the decision-making process can be complex and time-consuming. Increasingly, there is a need for effective polypharmacy management tools that can support short-staffed primary care practitioners.

In a new study, researchers from the Mass General Brigham MESH Incubator found that ChatGPT, a generative artificial intelligence (AI) chatbot, showed promise as a tool to manage polypharmacy and de-prescription. The findings, published in the Journal of Medical Systems, demonstrate the first use case of AI models in medicine management.

To evaluate its utility, the investigators provided ChatGPT with different clinical scenarios and asked it a set of decision-making questions. Each scenario featured the same elderly patient taking a mixture of medications but included variations in cardiovascular disease history (CVD) and degree of impairment in activities of daily living (ADL).

When asked yes or no questions about reducing prescribed drugs, ChatGPT consistently recommended deprescribing medications in patients without a history of CVD. However, it was more cautious when overlying CVD was introduced, and more likely to keep the patient’s medication regimen unchanged. In both cases, the researchers observed that ADL impairment severity did not seem to affect decision outcomes.

The team also noted that ChatGPT had a tendency to disregard pain and favoured de-prescribing pain medications over other drug types like statins or antihypertensives. In addition, ChatGPT responses varied when presented with the same scenario in new chat sessions — which the authors suggest could reflect inconsistency in commonly reported clinical deprescribing trends on which the model was trained.

More than 40 per cent of older adults meet the criteria for polypharmacy. The rate of seniors on Medicare seeing more specialists on their care teams has increased in recent years, leaving primary care providers to oversee medication management. An effective AI tool could help aid this practice, according to the researchers.

“Our study provides the first use case of ChatGPT as a clinical support tool for medication management,” said senior corresponding author Marc Succi, MD, Associate Chair of Innovation and Commercialization at Mass General Brigham Radiology and Executive Director of the MESH Incubator.

“While caution should be taken to increase accuracy of such models, AI-assisted polypharmacy management could help alleviate the increasing burden on general practitioners. Further research with specifically trained AI tools may significantly enhance the care of aging patients.”

Arya Rao, lead author, MESH researcher and Harvard Medical student, added: “Our findings suggest that AI-based tools can play an important role in ensuring safe medication practices for older adults; it is imperative that we continue to refine these tools to account for the complexities of medical decision-making.”

Read more in the Journal of Medical Systems.

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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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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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