dc.contributor.author | Ibáñez Solé, Olga | |
dc.contributor.author | Barrio Beraza, Irantzu | |
dc.contributor.author | Izeta Permisán, Ander | |
dc.date.accessioned | 2023-05-11T17:03:04Z | |
dc.date.available | 2023-05-11T17:03:04Z | |
dc.date.issued | 2023-04 | |
dc.identifier.citation | iScience 26(4) : (2023) // Article ID 106368 | es_ES |
dc.identifier.issn | 2589-0042 | |
dc.identifier.uri | http://hdl.handle.net/10810/61093 | |
dc.description.abstract | DNA damage has long been advocated as a molecular driver of aging. DNA damage occurs in a stochastic manner, and is therefore more likely to accumulate in longer genes. The length-dependent accumulation of transcription-blocking damage, unlike that of somatic mutations, should be reflected in gene expression datasets of aging. We analyzed gene expression as a function of gene length in several single-cell RNA sequencing datasets of mouse and human aging. We found a pervasive age-associated length-dependent underexpression of genes across species, tissues, and cell types. Furthermore, we observed length-dependent underexpression associated with UV-radiation and smoke exposure, and in progeroid diseases, Cockayne syndrome, and trichothiodystrophy. Finally, we studied published gene sets showing global age-related changes. Genes underexpressed with aging were significantly longer than overexpressed genes. These data highlight a previously undetected hallmark of aging and show that accumulation of genotoxicity in long genes could lead to reduced RNA polymerase II processivity. | es_ES |
dc.description.sponsorship | This work was supported by grants from Instituto de Salud Carlos III (PI22/01247 and PI19/01621), co-funded by the European Union, and Diputación Foral de Gipuzkoa. OI-S received the support of a fellowship from “Programa Investigo” of Lanbide-Servicio Vasco de Empleo, co-funded by the European Union (NextGenerationEU), la Caixa Foundation (ID 100010434; code LCF/BQ/IN18/11660065), and from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 713673. The work of IB was financially supported in part by grants from the Departamento de Educación, Política Lingüística y Cultura del Gobierno Vasco [IT1456-22] and by the Ministry of Science and Innovation through BCAM Severo Ochoa accreditation [CEX2021-001142-S/MICIN/AEI/10.13039/501100011033] and through project [PID2020-115882RB-I00/AEI/10.13039/501100011033] funded by Agencia Estatal de Investigación and acronym “S3M1P4R” and also by the Basque Government through the BERC 2022–2025 program. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/2020/713673 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/CEX2021-001142-S | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2020-115882RB-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | biological sciences | es_ES |
dc.subject | mMolecular biology | es_ES |
dc.subject | molecular genetics | es_ES |
dc.subject | omics | es_ES |
dc.subject | transcriptomics | es_ES |
dc.title | Age or lifestyle-induced accumulation of genotoxicity is associated with a length-dependent decrease in gene expression | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2023 The Author(s).
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0 | es_ES |
dc.rights.holder | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S2589004223004455?via%3Dihub | es_ES |
dc.identifier.doi | 10.1016/j.isci.2023.106368 | |
dc.contributor.funder | European Commission | |
dc.departamentoes | Matemáticas | es_ES |
dc.departamentoeu | Matematika | es_ES |