Published on: Jun 09, 2025
Researchers at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), have developed LinAge2, a next-generation biological ageing clock that gives healthcare professionals a more precise and practical tool to assess how quickly someone is ageing — and what can be done to slow it down.
Building upon earlier models like PCAge and LinAge, which utilized blood and urine tests alongside health questionnaires, LinAge2 improves on their predictive capabilities, offering enhanced accuracy, interpretability, and ease of use. While PCAge had already outperformed conventional cardiovascular risk scores and forecasted ageing-related decline before disease onset, LinAge2 advances these capabilities further, marking a significant step forward in clinical application.
Published in npj Aging, LinAge2 not only surpassed earlier clinical models but also outperformed leading epigenetic clocks in predicting long-term mortality and overall health. Key insights from the study include:
Superior mortality prediction: LinAge2 proved more accurate than chronological age and top biological clocks at forecasting 10- and 20-year mortality risks.
Correlation with functional health: Individuals with lower LinAge2 biological age were found to walk faster, think more clearly, and live more independently.
Actionable diagnostics: The tool identifies specific risk factors—such as smoking or metabolic syndrome—that are accelerating biological ageing, enabling clinicians to intervene more effectively.
“Chronological age doesn’t reflect our actual health status,” explained Associate Professor Jan Gruber, senior author and principal investigator at the Department of Biochemistry and Healthy Longevity Translational Research Programme (TRP) at NUS Medicine. “Biological ageing clocks like LinAge2 offer a more holistic measure of how fast a person is really ageing inside. This can help guide personalised treatments and lifestyle changes to extend healthy years of life.”
The LinAge2 model was tested not only for mortality prediction but also for functional health metrics such as gait speed, cognition, and daily living independence. It consistently outperformed DNA methylation-based clocks like PhenoAge and GrimAge2. Its usability was enhanced by simplifying lab test requirements, accounting for gender differences, and minimizing skew from outliers. A user-friendly visual interface also allows clinicians and researchers to pinpoint which factors are driving an individual’s biological ageing.
Developed in collaboration with Dr. Fong Sheng, Consultant in Geriatric Medicine at Ng Teng Fong General Hospital, the ultimate aim is to integrate tools like LinAge2 into routine clinical care. “By identifying patients who are ageing faster biologically, we can intervene earlier—whether through lifestyle modification, medical treatment, or preventive care,” Dr. Fong said. “This means improving not just how long people live, but how well they live.
Associate Professor Gruber concluded, “We envision a future of personalised, preventive, and proactive medicine—where we treat ageing itself, not just the diseases it causes.
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