Nuclear envelope disruption triggers hallmarks of aging in lung alveolar macrophages.

Autor: De Silva NS; Institut Curie, PSL Research University, INSERM U932, Paris, France., Siewiera J; Institut Curie, PSL Research University, INSERM U932, Paris, France., Alkhoury C; Institut Curie, PSL Research University, INSERM U932, Paris, France., Nader GPF; Institut Curie, PSL Research University, CNRS UMR144, Paris, France., Nadalin F; Institut Curie, PSL Research University, INSERM U932, Paris, France., de Azevedo K; Institut Curie, PSL Research University, INSERM U932, Paris, France., Couty M; Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Team van Niel, Paris, France., Izquierdo HM; Institut Curie, PSL Research University, INSERM U932, Paris, France., Bhargava A; Institut Curie, PSL Research University, INSERM U932, Paris, France., Conrad C; Institut Curie, PSL Research University, INSERM U932, Paris, France., Maurin M; Institut Curie, PSL Research University, INSERM U932, Paris, France., Antoniadou K; Institut Curie, PSL Research University, INSERM U932, Paris, France., Fouillade C; Institut Curie, PSL Research University, Université Paris-Saclay, CNRS, INSERM, UMR3347, U1021, Orsay, France., Londono-Vallejo A; Institut Curie, PSL Research University, CNRS UMR3244, Paris, France., Behrendt R; Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany., Bertotti K; Biocellvia, Marseille, France., Serdjebi C; Biocellvia, Marseille, France., Lanthiez F; Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France., Gallwitz L; Biochemical Institute, Christian-Albrechts-University Kiel, Kiel, Germany., Saftig P; Biochemical Institute, Christian-Albrechts-University Kiel, Kiel, Germany., Herrero-Fernández B; Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid (UAM), Madrid, Spain., Saez A; Facultad de Ciencias Experimentales, Universidad Francisco de Vitoria (UFV), Pozuelo de Alarcón, Spain., González-Granado JM; LamImSys Lab, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12). Department of Immunology, Ophthalmology and ENT, School of Medicine, Universidad Complutense de Madrid. CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain., van Niel G; Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Team van Niel, Paris, France., Boissonnas A; Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, Paris, France., Piel M; Institut Curie, PSL Research University, CNRS UMR144, Paris, France., Manel N; Institut Curie, PSL Research University, INSERM U932, Paris, France. nicolas.manel@curie.fr.
Jazyk: angličtina
Zdroj: Nature aging [Nat Aging] 2023 Oct; Vol. 3 (10), pp. 1251-1268. Date of Electronic Publication: 2023 Sep 18.
DOI: 10.1038/s43587-023-00488-w
Abstrakt: Aging is characterized by gradual immune dysfunction and increased disease risk. Genomic instability is considered central to the aging process, but the underlying mechanisms of DNA damage are insufficiently defined. Cells in confined environments experience forces applied to their nucleus, leading to transient nuclear envelope rupture (NER) and DNA damage. Here, we show that Lamin A/C protects lung alveolar macrophages (AMs) from NER and hallmarks of aging. AMs move within constricted spaces in the lung. Immune-specific ablation of lamin A/C results in selective depletion of AMs and heightened susceptibility to influenza virus-induced pathogenesis and lung cancer growth. Lamin A/C-deficient AMs that persist display constitutive NER marks, DNA damage and p53-dependent senescence. AMs from aged wild-type and from lamin A/C-deficient mice share a lysosomal signature comprising CD63. CD63 is required to limit damaged DNA in macrophages. We propose that NER-induced genomic instability represents a mechanism of aging in AMs.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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