Scientists found that tiny RNA molecules in the bloodstream - known as piRNAs - were stronger predictors of short-term survival than age, cholesterol or lifestyle factors.
A simple blood test could help identify which older adults are at higher risk of dying within two years, according to new research.
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The study, which was led by Duke Health alongside the University of Minnesota, suggests that tiny RNA molecules found in the bloodstream may offer a new way to assess short-term survival risk in people aged 71 and older.
Researchers focused on small RNA fragments known as PIWI-interacting RNAs (piRNAs), which are involved in regulating development, regeneration, and immune function. By analysing blood samples from more than 1,200 older adults, researchers discovered that lower levels of certain piRNAs were linked to longer survival.
"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,” said Virginia Byers Kraus, a senior author of the study and professor in the departments of Medicine, Pathology and Orthopaedic Surgery at Duke University School of Medicine.
"What surprised us most was that this powerful signal came from a simple blood test," Kraus added.
How was the study carried out and what were the results?
Using artificial intelligence and machine learning, the team examined 187 different health measures alongside 828 small RNAs.
Advanced modelling showed that just six piRNAs could predict two-year survival with up to 86 percent accuracy. These findings were confirmed in a second, independent group of older adults.
For short-term survival, piRNAs outperformed age, cholesterol levels, physical activity, and more than 180 other clinical measures.
Participants who lived longer consistently showed lower levels of specific piRNAs - a pattern that mirrors findings in laboratory organisms. In C. elegans (tiny roundworms), for example, reducing global piRNA levels has been shown to double lifespan.
"We know very little about piRNAs in the blood, but what we’re seeing is that lower levels of certain specific ones is better," Kraus said. "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."
Can treatments alter these blood molecules?
The team now plans to investigate whether treatments, lifestyle changes, or medications - including emerging drug classes such as GLP-1 drugs - could alter piRNA levels.
They also aim to compare levels in blood with those found in tissues to better understand how the molecules function.
“These small RNAs are like micromanagers in the body, helping control many processes that affect health and aging,” Kraus said. "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.”
