biostudies-literatureRomero-Bueno RMEC | Agencia Estatal de Investigación (AEI)Vetenskapsrådet (VR)VetenskapsrådetMEC | Consejo Superior de Investigaciones Científicas (CSIC)Cancerfonden (Swedish Cancer Society)European Molecular Biology Organization (EMBO)National Science Foundation (NSF)MEC | Consejo Superior de Investigaciones CientíficasCancerfondenEuropean Molecular Biology OrganizationMEC | Agencia Estatal de InvestigaciónNovo Nordisk Fonden (NNF)Novo Nordisk FondenKarolinska Institutet Doctoral Education GrantNIH HHSNational Science Foundation5718-5746https://www.ebi.ac.uk/biostudies/studies/S-EPMC11574047biostudies-literatureUnknown43(22)Alterations in the nuclear envelope are linked to a variety of rare diseases termed laminopathies. A single amino acid substitution at position 12 (A12T) of the human nuclear envelope protein BAF (Barrier to Autointegration Factor) causes Néstor-Guillermo Progeria Syndrome (NGPS). This premature ageing condition leads to growth retardation and severe skeletal defects, but the underlying mechanisms are unknown. Here, we have generated a novel in vivo model for NGPS by modifying the baf-1 locus in C. elegans to mimic the human NGPS mutation. These baf-1(G12T) mutant worms displayed multiple phenotypes related to fertility, lifespan, and stress resistance. Importantly, nuclear morphology deteriorated faster during aging in baf-1(G12T) compared to wild-type animals, recapitulating an importantThe EMBO journalA human progeria-associated BAF-1 mutation modulates gene expression and accelerates aging in C. elegans.PMC11574047CEX2020-001088-MNNF22OC0078353PID2022-137162NB-I00VR2023-043832023AEP058PID2019-105069GB-I00KIDSEG9276P40 OD010440CAREER award 194292223 2994 PjBES-2017-080216Riedel CGWard JDFragoso-Luna AAskjaer PRomero-Bueno RAyuso CMellmann NKavsek AfalseA human progeria-associated BAF-1 mutation modulates gene expression and accelerates aging in C. elegans.Alterations in the nuclear envelope are linked to a variety of rare diseases termed laminopathies. A single amino acid substitution at position 12 (A12T) of the human nuclear envelope protein BAF (Barrier to Autointegration Factor) causes Néstor-Guillermo Progeria Syndrome (NGPS). This premature ageing condition leads to growth retardation and severe skeletal defects, but the underlying mechanisms are unknown. Here, we have generated a novel in vivo model for NGPS by modifying the baf-1 locus in C. elegans to mimic the human NGPS mutation. These baf-1(G12T) mutant worms displayed multiple phenotypes related to fertility, lifespan, and stress resistance. Importantly, nuclear morphology deteriorated faster during aging in baf-1(G12T) compared to wild-type animals, recapitulating an important2024-01-01T00:00:00Z2024 Nov2026-06-02T16:12:19.502Z2025-04-04T11:42:53.81ZS-EPMC115740473936723410.1038/s44318-024-00261-8