A new Nature Aging study suggests that senescent cells may drive inflammaging through a previously underappreciated mechanism: the nuclear export of R-loops.
The authors show that R-loops, normally nuclear DNA–RNA hybrid structures, can be exported into the cytoplasm through a DDX1–XPO1 complex in senescent cells. Once in the cytoplasm, these R-loops activate the cGAS–STING pathway, amplifying the SASP and systemic inflammation.
In old mice, blocking XPO1 with selinexor reduced cytoplasmic R-loops, dampened inflammatory markers, improved several aging-related phenotypes, and modestly extended survival.
However, selinexor is an anticancer drug with significant toxicity, so this is not directly translatable as an anti-aging intervention. The real interest is the pathway: targeting R-loop export or downstream cGAS–STING activation could become a promising strategy to reduce inflammaging without necessarily killing senescent cells.