A handful of tiny molecules circulating in the blood may help identify which older adults 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 71 and older, six small RNA molecules in the blood, called piRNAs, predicted short-term survival with up to 86 percent accuracy — better than using age, cholesterol, physical activity or more than 180 other standard health measures.
“These RNAs are linked to survival,” and the analysis suggests they may also influence whether someone survives, says rheumatologist Virginia Byers Kraus of Duke University.
PiRNAs, short for piwi-interacting RNAs, help regulate genes involved in development, tissue repair and immune function. Research in roundworms shows that reducing piRNAs can double life span, and though widely studied in animals, their role in human aging has remained unclear.
Kraus and her colleagues collected blood samples from volunteers in a long-running North Carolina health study. 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 healthy aging. 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 for short-term survival. This pattern was validated in a separate group of participants.
The further into the future the researchers looked, the more influence lifestyle and traditional health factors had, though piRNAs still highlighted underlying biological differences, such as how cells handle stress, repair damage and age over time. When, in computer simulations, the researchers tweaked patients’ piRNA levels to ideal levels, the predicted two-year survival increased from roughly 47 percent to nearly 100 percent.
While the results are exciting, those simulations should be interpreted cautiously, says Yale University computational biologist Raghav Sehgal. The analysis assumes extreme changes in piRNA levels that may not be biologically feasible or safe.
At this stage, Sehgal says, the piRNA patterns probably reflect short-term health risks or frailty rather than gradual biological aging, so the test is not yet ready for clinical use. The results need confirmation in other studies and may vary depending on testing methods or in younger populations.
Kraus and her team plan to explore piRNA patterns across people ages 30 to 100 and test whether interventions such as the diabetes drug metformin or GLP-1 drugs could modify RNA levels and improve health outcomes. The researchers hope to identify which RNA patterns signal higher risk and who might benefit most if such treatments eventually reach the clinic.
