Levels of six RNA molecules helped identify older people most likely to survive two more years
A handful of tiny molecules circulating in the blood could help identify which elderly people are most likely to survive the next two years, researchers report February 24 in Aging cell.
In a study of more than 1,200 people aged 71 and older, six small RNA molecules found in the blood, called piRNAs, predicted short-term survival with up to 86% accuracy – better than using age, cholesterol, physical activity or over 180 other standard health measures.
“These RNAs are linked to survival,” and the analysis suggests they may also influence a person’s survival, says rheumatologist Virginia Byers Kraus of Duke University.
PiRNA, short for RNA interacting with piwishelp regulate genes involved in development, tissue repair and immune function. Research on roundworms shows that reducing piRNAs can double lifespanand yet widely studied in animalstheir role in human aging remains unclear.
Kraus and his colleagues collected blood samples from volunteers as part of a long-term health study in North Carolina. The team analyzed 828 small RNAs, including piRNAs, in plasma, along with other health indicators from medical records, in-person physical and cognitive assessments, and participants’ self-reported lifestyle data.
The team identified nine piRNAs associated with age healthily. People who lived longer consistently had lower levels of these molecules. In particular, the combined levels of six of these piRNAs emerged as the strongest predictor of short-term survival. This model was validated in a separate group of participants.
The farther into the future researchers looked, the more influence traditional lifestyle and health factors had, although piRNAs still highlighted underlying biological differences, such as how cells handle stress, repair damage and age over time. When, in computer simulations, the researchers adjusted patients’ piRNA levels to ideal levels, predicted two-year survival increased from about 47 percent to almost 100 percent.
Although the results are exciting, these simulations should be interpreted with caution, says Raghav Sehgal, a computational biologist at Yale University. The analysis assumes extreme changes in piRNA levels that might not be biologically feasible or safe.
At this point, Sehgal says, the piRNA patterns likely reflect short-term health risks or fragility rather than progressive biological aging, so the test is not yet ready for clinical use. Results need to be confirmed by other studies and may vary depending on testing methods or in younger populations.
Kraus and his team plan to explore piRNA patterns in people aged 30 to 100 and test whether interventions such as the diabetes drug metformin, or GLP-1 drugs could alter RNA levels and improve health outcomes. Researchers hope to identify which RNA patterns signal higher risk and who could benefit most if such treatments ultimately reach the clinic.