Research into ageing is producing an overwhelming amount of data, making it difficult to determine which interventions — such as new medicines, dietary changes, or exercise routines — are safe and effective. This study investigated how AI can analyse data more efficiently and accurately, by proposing a comprehensive set of standards for AI systems to ensure they deliver accurate, reliable, and understandable evaluations through their ability to analyse complex biological data.

The researchers identified eight critical requirements for effective AI-based evaluations:

1. Correctness of the evaluation results. Data quality will be assessed for accuracy.
2. Usefulness and comprehensiveness.
3. Interpretability and explainability of the evaluation results. Clarity and conciseness of the results and the given explanations.
4. Specific consideration of causal mechanisms affected by the intervention.
5. Consideration of data in a holistic context:
   1. Efficacy and toxicity, and evidence for the existence of a large therapeutic window;
   2. Analyses in an “interdisciplinary” setting.
6. Enabling reproducibility, standardisation, and harmonisation of the analyses (and of the reporting).
7. Specific emphasis on diverse longitudinal large-scale data.
8. Specific emphasis on results that relate to known mechanisms of ageing.

Telling LLMs about these requirements as part of the prompting improved the quality of the recommendations they produced.

Professor Brian Kennedy from the Department of Biochemistry & Physiology, and Healthy Longevity Translational Research Programme at NUS Medicine, who co-led the study, said, “We tested AI methods using real-world examples such as medicines and dietary supplements. We found that by following specific guidelines, AI can provide more accurate and detailed insights. For instance, when analysing rapamycin, a drug often studied for its potential to promote healthy ageing, the AI not only evaluated its efficacy but also provided context-specific explanations and caveats, such as possible side effects.”

“The study’s findings could have far-reaching effects,” added Professor Georg Fuellen, Director, Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, who co-led the study, “For healthcare, telling the AI about the critical requirements of a good response can enable it to find more effective treatments and make them safer to use. Generally, AI tools could design better clinical trials and help tailor health recommendations to each person. This research is a major step toward using AI to improve health outcomes for everyone, especially as they age.”

Moving forward, the team is now focusing on a large-scale study of how to best prompt AI models for longevity-related intervention advice, to evaluate their accuracy and reliability for a wide array of carefully designed benchmarks, that is, curated, high-quality data. The validation of such AI systems is specifically important because the longevity interventions may then be implemented by a large number of healthy people. Prospective studies will need to demonstrate that AI-based evaluations can accurately predict successful outcomes in human trials, paving the way for safer and more effective health interventions.

The team hopes to use their findings to make health and longevity interventions more precise and accessible, and ultimately improve the quality and duration of life. Collaboration between researchers, clinicians, and policymakers will be essential to establish robust regulatory frameworks, ensuring the safe and effective use of AI-driven evaluations.

An emerging area of research is the evolutionarily conserved transfer of mitochondria between cells. Yet researchers have lacked unique and universally accepted terms and practices to describe such transfers. Absent an agreed nomenclature and standard practices, different researchers may use different methods and terminology to describe the same event, or they may employ the same term that actually describe two different processes.

“Over the past few years, we have come to understand that mitochondria can be transferred from one cell to another, and that isolated mitochondria can be transplanted like an organ transplant,” said Keshav K. Singh, Ph.D., professor in the University of Alabama at Birmingham Department of Genetics. “Though the origins of mitochondria transfer are unclear, it has been observed in evolutionarily diverse eukaryotes, including yeast, mollusks, fish and rodents, as well as human cells. We are just beginning to understand how alterations in this process contribute to disease pathogenesis and how to harness mitochondria transfer and transplantation biology to develop new therapies.”

In 2024, Singh and Jonathan Brestoff, M.D., Ph.D., Washington University School of Medicine, Saint Louis, Missouri, set up an international consortium on mitochondria transfer and transplantation and led an international team of 31 researchers to develop consensus and recommendations about how to advance the field by providing common terminology and characterizations for the transfer or transplantation of mitochondria. Their consensus paper, “Recommendations for mitochondria transfer and transplantation nomenclature and characterization,” is published in the journal Nature Metabolism.

The paper begins with a brief history of the field — some foundational early discoveries, recent studies of mitochondrial transfer and development of therapeutic approaches, including cell engineering and clinical trials for children requiring extracorporeal membrane oxygenation.

The paper defines types of mitochondria transfer and mitochondria transplantation, and when both the donor and acceptor cell types are established in vivo, that defines a mitochondria transfer axis. The paper reviews methods to define mitochondria transfer, including mitochondria reporter proteins and dyes, methods to enforce transfer, and discussion of the fate of mitochondria after cell entry. Mechanism-based nomenclature is roughly grouped into contact-dependent mitochondria transfer, where the donor cell and recipient cell touch each other, and contact-independent mitochondria transfer.

The recommendations also review therapeutic approaches of mitochondria transplantation, including the definition of transplants; the types, durability, degree of engraftment and heterogeneity of transplants; cell engineering using extracellular mitochondria; and drugs that affect mitochondria transfer. Extracellular mitochondria are common in humans — for example there are about 3 billion to 12 billion extracellular mitochondria in a unit of blood platelets, a blood product that is routinely and safely transfused to patients intravenously.

The paper concludes that “the goal of this proposed nomenclature is to reduce the confusion that can be caused by the introduction of different names for similar processes or extracellular mitochondria subsets as this field has evolved. We recognize that mitochondria transfer and transplantation are very active areas of research and that it is possible that new findings and insights may necessitate updates to the proposed nomenclature.”

Singh has a long-standing interest in mitochondria. He was founding editor-in-chief of the journal Mitochondrion and the founder of the Society for Mitochondria Research and Medicine. In 2007 and 2009, his laboratory showed that isolated mouse mitochondria can be transferred to human cells by co-incubation, providing a proof of principle for transfer of mitochondria by diffusion, and that xeno-transplanted platelet mitochondria from an African American woman who suffered aggressive breast cancer at young age was able to recapitulate aggressiveness of breast cancer in mice. At that time, these findings were not appreciated by the field, Singh says.

The increase in physical activity was mainly seen in those doing semi-routine occupations such as bus driving or hairdressing, and routine occupations such as cleaning or waiting, or technical jobs. There was little change seen among people entering managerial or professional occupations.

The largest drop in levels of physical activity was seen among people who work from home — though their sleep levels did not change when they started work.

Young adulthood — ages 16 to 30 years — is an important time in terms of health. Although we are typically at our peak physical health, it is also a time when many risk factors for long term diseases such as heart disease, type 2 diabetes and cancer begin to develop.

Health guidelines recommend young adults get between seven and nine hours of sleep a night, engage in 150 minutes or more of moderate physical activity per week, and consume at least five portions of fruit and vegetables per day.

Young adulthood is also the time when most people start work, which changes their daily routines and activities, resources such as time and money, and social and physical environments — all of which affect health behaviours and health in later life.

To quantify the impact that starting work has on health-related behaviours, a team led by researchers at the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge examined repeated data taken over time from more than 3,000 participants in the UK Household Longitudinal Study. All the participants were aged 16-30 years and started work for the first time between 2015 and 2023.

The results are published today in the International Journal of Behavioral Nutrition and Physical Activity.

Dr Eleanor Winpenny, who was based at the University of Cambridge when she carried out the work, but is now at Imperial College London, said: “We know about physical activity and sleep patterns among young people while they’re at school, but very little about what happens when they start work. Given the impact that work can have on our lives — and the lasting impacts this can have on our health — it’s important to try and understand what happens at this transition.”

The analysis showed that when people started work, their physical activity increased by an amount equivalent to around 28 min of moderate activity (such as cycling) per day on average — but then decreased each year after starting work by around 7 min per day.

The biggest increase was among males — up by an equivalent of around 45 min of moderate activity per day compared to an increase of around 16 min for females. People who did not have a university degree also showed a greater increase in physical activity compared to those with a university degree — equivalent to around a 42 min increase of moderate physical activity per day compared to 15 min per day.

Working from home, however, appeared to be associated with an initial decrease in physical activity, equivalent to around 32 min of moderate activity per day.

When young adults started work, the amount of time they slept per night dropped immediately by almost 10 minutes and remained stable at this level over time; however, people without a degree showed a continuing decrease of about 3 minutes of sleep per night each year after starting work, while those with a degree slowly increased back to their pre-work sleep levels.

There was little change in the amount of fruit and vegetables consumed after starting work.

Alena Oxenham, from the MRC Epidemiology Unit, said: “Beginning work can have a profound impact on our lifestyles and on behaviours that might make a difference to our health, if not immediately then later in life.

“Although we found that people tend to do more physical activity when they begin work, which is good news, these are averages, and some people — particularly those who work from home and, to a lesser degree, those with office-based jobs — may do less.

“If we want to stay healthy throughout our lives, we need to remember that keeping active is an important way of helping us achieve this goal. Those working at home might want to consider incorporating physical activity into their day, for example by going for a walk before or after work, or during a lunch break.”

Dr Winpenny added: “Workplaces provide an opportunity to create environments and cultures that support healthier diets, more physical activity and better sleep for young adults. This could result in healthier employees and fewer sick days in the immediate term, but also have long term benefits, helping prevent health issues in later life.”

The findings, presented today at the American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Annual Symposium and published in Nature Medicine, demonstrated a 60.9% overall response rate (ORR) with the three-drug combination compared to 40% with the standard-of-care (SOC) treatment — chemotherapy with or without bevacizumab. In the experimental arm, 68.7% of patients had a duration of response of at least six months, compared to 34.1% of patients in the SOC arm.

Data from this multi-institutional collaboration across 28 countries supported the accelerated approval of this combination by the Food and Drug Administration (FDA) in Dec. 2024, providing an effective new first-line treatment option for patients with BRAF V600E-mutant mCRC.

“Chemotherapy has had limited efficacy as a first-line treatment in controlling the aggressive tumor growth we see in patients with this mutation,” said co-principal investigator Scott Kopetz, M.D., Ph.D., professor of Gastrointestinal Medical Oncology and associate vice president of Translational Integration at MD Anderson. “This new regimen highlights the importance of combining dual-targeted therapy with chemotherapy to improve patient outcomes in the first-line setting, and the durable responses are a significant development as we work to improve quality of life for these patients.”

More than 150,000 people are diagnosed with colorectal cancer each year, making it the fourth most common cancer in the U.S., according to the National Cancer Institute. BRAF mutations occur in approximately 8-12% of cases and are associated with aggressive tumor growth, low efficacy from SOC treatments and a poor prognosis, with a median overall survival less than 12 months. Previously, there were no first-line targeted therapies approved for patients with BRAF V600E-mutant mCRC.

The BREAKWATER trial was one of the first studies to utilize the FDA’s Project FrontRunner, an initiative to encourage the evaluation of therapies in earlier clinical settings for advanced cancers rather than after patients received numerous previous treatments.

The trial enrolled patients who were at least 16 years of age with previously untreated BRAF V600E-mutant mCRC. Patients were randomized equally to one of three treatment arms: SOC chemotherapy with or without bevacizumab; a dual combination of encorafenib plus cetuximab; or a triple combination of encorafenib, cetuximab and mFOLFOX6.

When researchers analyzed patient subgroups on the trial, the triple combination showed benefits across important groups, including patients with cancer spread to three or more organs and those with liver metastases.

“These results support this combination as a new first-line standard of care for patients with BRAF V600E-mutant metastatic colorectal cancer,” Kopetz said. “It also highlights the importance of swiftly identifying molecular subtypes of colorectal cancer at diagnosis to optimize treatment strategies for our patients.”

The safety profile of this combination was consistent with the known safety profile of each respective drug. No new safety signals were identified. The most common adverse reactions included nausea, rash, fatigue, vomiting, abdominal pain, diarrhea and decreased appetite, all of which were reported in at least 25% of patients and were similar between arms.

Final calculations of progression-free survival and overall survival will be formally assessed in the next phase of the trial. Future analyses of this trial may shed light on predictive biomarkers for this combination therapy.

The study was sponsored by Pfizer Inc., and Kopetz disclosed consulting for Pfizer and receiving research funding from the company.