Scientists uncover how R-loops fuel aging—and a drug that may reverse it

Researchers at The University of Texas MD Anderson Cancer Center have uncovered a new molecular link between R-loops and chronic inflammation in aged tissues. Their findings suggest that blocking the export of these nucleic acid structures from the nucleus could delay age-related decline and extend healthspan in animal models. The study identified R-loops as key structures exported from the nucleus to the cytoplasm in senescent cells. Once in the cytoplasm, they bind to DNA fragments and trigger an immune alarm, leading to widespread inflammation. Researchers pinpointed DDX1 and XPO1 as the proteins responsible for this export process.

In preclinical tests, the FDA-approved drug selinexor was used to inhibit XPO1. This trapped R-loops inside the nucleus, preventing their mislocalisation and reducing systemic inflammation. Treated models showed improvements in liver fibrosis, fat accumulation, and muscle wasting.

The results indicate that targeting nucleic acid trafficking could be a viable strategy for countering age-associated dysfunction. Selinexor’s role as a proof-of-concept therapy highlights the potential of precision medicine in addressing aging as a modifiable condition. The study opens new avenues for delaying age-related decline by modulating R-loop export. Clinical trials are now needed to assess the safety and efficacy of nuclear export inhibitors in older populations. Monitoring immune function will be essential during these evaluations.