Duke-led study finds piRNAs in blood samples can predict two-year survival with up to 86% accuracy, outperforming traditional health measures.
A blood test measuring small RNA molecules can accurately predict whether older adults are likely to survive at least two more years, according to new research from Duke Health published in Aging Cell.
The study found that small RNA molecules known as piRNAs (PIWI-interacting RNAs) were the strongest predictor of two-year survival in older adults—more accurate than age, lifestyle habits, or other health measures examined by researchers.
“The combination of just a few piRNAs was the strongest predictor of two-year survival in older adults—stronger than age, lifestyle habits, or any other health measures we examined,” says Virginia Byers Kraus, MD, PhD, senior author of the study and professor in the departments of Medicine, Pathology and Orthopaedic Surgery at Duke University School of Medicine, in a release. “What surprised us most was that this powerful signal came from a simple blood test.”
Machine Learning Analysis of Blood Samples
Researchers used causal artificial intelligence and machine learning approaches to analyze 187 clinical factors and 828 different small RNAs in more than 1,200 blood samples from adults aged 71 and older. The samples were drawn from a large North Carolina-based cohort established in a previous Duke-led study, with survival outcomes determined by linking participants to national mortality records.
Advanced statistical modeling revealed that a group of six piRNAs alone predicted two-year survival with accuracy as high as 86%. The team confirmed the findings in a second, independent group of older adults.
The study found that participants who lived longer consistently had lower levels of specific piRNAs, echoing a pattern seen in simple organisms where reducing these molecules can extend lifespan. Past studies have shown these small bits of RNA regulate development, regeneration and the immune system.
Outperforming Traditional Health Indicators
For predicting short-term survival, piRNAs outperformed age, cholesterol, physical activity, and more than 180 other clinical measures. For longer-term survival, lifestyle factors became more influential, but piRNAs continued to provide valuable insight into underlying biology.
“We know very little about piRNAs in the blood, but what we’re seeing is that lower levels of certain specific ones is better,” says Kraus in a release. “When these molecules are present in higher amounts, it may signal that something in the body is off-track. Understanding why could open new possibilities for therapies that promote healthy aging.”
The findings suggest that a blood test could one day help identify survival risks earlier and guide treatment strategies to promote healthy aging, according to researchers.
Next Steps for Research
The team’s next steps include studying whether treatments, lifestyle changes, or medications—including emerging drug classes like GLP-1 based therapies—might alter piRNA levels. They also plan to compare piRNA levels in blood with levels inside tissues to better understand how these molecules function.
“These small RNAs are like micromanagers in the body, helping control many processes that affect health and aging,” says Kraus in a release. “We are only beginning to understand how powerful they are. This research suggests we should be able to identify short-term survival risk using a practical, minimally invasive blood test—with the ultimate goal of improving health as we age.”
The work was funded by the National Institutes of Health, the National Institute on Aging, the National Center for Advancing Translational Sciences, and the National Heart, Lung, and Blood Institute.
Photo caption: Virginia Byers Kraus, MD, PhD, in the lab
Photo credit: Duke University Medical Center
