biostudies-literatureKumar AVNIA NIH HHSNIH HHSeabj1604https://www.ebi.ac.uk/biostudies/studies/S-EPMC10938577biostudies-literatureUnknown8(13)Altered nucleolar and ribosomal dynamics are key hallmarks of aging, but their regulation remains unclear. Building on the knowledge that the conserved nuclear export receptor Exportin 1 (XPO-1/XPO1) modulates proteostasis and life span, we systematically analyzed the impact of nuclear export on protein metabolism. Using transcriptomic and subcellular proteomic analyses in nematodes, we demonstrate that XPO-1 modulates the nucleocytoplasmic distribution of key proteins involved in nucleolar dynamics and ribosome function, including fibrillarin (FIB-1/FBL) and RPL-11 (RPL11). Silencing <i>xpo-1</i> led to marked reduction in global translation, which was accompanied by decreased nucleolar size and lower fibrillarin levels. A targeted screen of known proteostatic mediators revealed that the Science advancesExportin 1 modulates life span by regulating nucleolar dynamics via the autophagy protein LGG-1/GABARAP.PMC10938577R01 AG051810R00 AG042494P40 OD010440R21 AG068922Rogers ANKang TThakurta TGNg CKumar AVLarsen MRLapierre LRfalseExportin 1 modulates life span by regulating nucleolar dynamics via the autophagy protein LGG-1/GABARAP.Altered nucleolar and ribosomal dynamics are key hallmarks of aging, but their regulation remains unclear. Building on the knowledge that the conserved nuclear export receptor Exportin 1 (XPO-1/XPO1) modulates proteostasis and life span, we systematically analyzed the impact of nuclear export on protein metabolism. Using transcriptomic and subcellular proteomic analyses in nematodes, we demonstrate that XPO-1 modulates the nucleocytoplasmic distribution of key proteins involved in nucleolar dynamics and ribosome function, including fibrillarin (FIB-1/FBL) and RPL-11 (RPL11). Silencing <i>xpo-1</i> led to marked reduction in global translation, which was accompanied by decreased nucleolar size and lower fibrillarin levels. A targeted screen of known proteostatic mediators revealed that the 2022-01-01T00:00:00Z2022 Apr2026-07-15T00:39:43.8Z2026-06-27T03:05:38.68ZS-EPMC109385773536352810.1126/sciadv.abj1604