GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296054/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296054GEOGSEfalseTargeting XPO1/DDX1-mediated nuclear export of R-loops in inflammaging [RIP-Seq]R-loops are three-stranded nucleic acids containing DNA-RNA hybrid and a third displaced ssDNA and are widely distributed across the genome. Dysregulation in R-loop dynamics cause DNA damage and genome instability. Although its role has been extensively investigated in various pathological processes, whether R-loops are perturbed during senescence and tissue aging remains unclear. Here we observe a global decline in R-loop stalling across the genome during senescence. While R-loops in nucleus were dramatically decreased, we detected their significant accumulation in the cytoplasm in senescent cells. We identify their source as nuclear R-loops with a specific enrichment in alpha-satellites, a subset of repetitive elements. Notably, these cytoplasmic R-loops localize into cytoplasmic chromatin fragments (CCF) to induce cGAS-STING innate immune response, and this nucleocytoplasmic transport is dependent on exportin 1 (XPO1)/DEAD-Box helicase 1 (DDX1) complex. Targeting R-loop nuclear export by XPO1 inhibitor Selinexor (KPT-330) suppresses the inflammatory response in senescent cells and relieves inflammaging in aged mice. In summary, our findings linked aberrant accumulation of cytoplasmic R-loops to inflammaging, rendering their nucleocytoplasmic transport process an ideal target for suppressing inflammaging.2026/04/30GSE296054GSM8964418GSM8964417GSM8964416GSM8964415GSM8964419GSM8964421GSM8964410GSM8964420GSM8964414GSM8964413GSM8964412GSM896441111154296054Homo sapiens