{"doi":"10.1038/s42003-022-03496-5","title":"Brain aging is faithfully modelled in organotypic brain slices and accelerated by prions","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Mammalian models are essential for brain aging research. However, the long lifespan and poor amenability to genetic and pharmacological perturbations have hindered the use of mammals for dissecting aging-regulatory molecular networks and discovering new anti-aging interventions. To circumvent these limitations, we developed an ex vivo model system that faithfully mimics the aging process of the mammalian brain using cultured mouse brain slices. Genome-wide gene expression analyses showed that cultured brain slices spontaneously upregulated senescence-associated genes over time and reproduced many of the transcriptional characteristics of aged brains. Treatment with rapamycin, a classical anti-aging compound, largely abolished the time-dependent transcriptional changes in naturally aged brain slice cultures. Using this model system, we discovered that prions drastically accelerated the development of age-related molecular signatures and the pace of brain aging. We confirmed this finding in mouse models and human victims of Creutzfeldt-Jakob disease. These data establish an innovative, eminently tractable mammalian model of brain aging, and uncover a surprising acceleration of brain aging in prion diseases.</jats:p>","journal":"Communications Biology","year":2022,"id":600104,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1538285,"name":"Assunta Senatore","orcid":null,"position":1,"is_corresponding":false},{"id":688268,"name":"Silvia Sorce","orcid":"0000-0002-3843-8644","position":2,"is_corresponding":false},{"id":176560,"name":"Mario Nuvolone","orcid":"0000-0001-8334-1684","position":3,"is_corresponding":false},{"id":150377,"name":"Jingjing Guo","orcid":null,"position":4,"is_corresponding":false},{"id":51787,"name":"Zeynep H. Gümüş","orcid":"0000-0002-7364-2202","position":5,"is_corresponding":false},{"id":300784,"name":"Adriano Aguzzi","orcid":"0000-0002-0344-6708","position":6,"is_corresponding":false},{"id":1538284,"name":"Yingjun Liu","orcid":"0000-0003-1543-1965","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Brain aging is faithfully modelled in organotypic brain slices and accelerated by prions","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Mammalian models are essential for brain aging research. However, the long lifespan and poor amenability to genetic and pharmacological perturbations have hindered the use of mammals for dissecting aging-regulatory molecular networks and discovering new anti-aging interventions. To circumvent these limitations, we developed an ex vivo model system that faithfully mimics the aging process of the mammalian brain using cultured mouse brain slices. Genome-wide gene expression analyses showed that cultured brain slices spontaneously upregulated senescence-associated genes over time and reproduced many of the transcriptional characteristics of aged brains. Treatment with rapamycin, a classical anti-aging compound, largely abolished the time-dependent transcriptional changes in naturally aged brain slice cultures. Using this model system, we discovered that prions drastically accelerated the development of age-related molecular signatures and the pace of brain aging. We confirmed this finding in mouse models and human victims of Creutzfeldt-Jakob disease. These data establish an innovative, eminently tractable mammalian model of brain aging, and uncover a surprising acceleration of brain aging in prion diseases.</jats:p>","is_dataset_classified":null,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35676449","pmcid":"PMC9177860","openalex_id":"https://openalex.org/W4282935960","authors":[],"funders":[{"funder_name":"Swiss National Science Foundation","grant_id":"179040","title":"The prion protein in health and disease"}],"total_grants":1,"fwci":0.3134,"citation_percentile":0.50268197,"influential_citations":0,"citation_trend":[{"year":2023,"count":1},{"year":2024,"count":1},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/s42003-022-03496-5.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/s42003-022-03496-5.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/s42003-022-03496-5","host_type":"publisher"},{"url":"https://doi.org/10.1038/s42003-022-03496-5","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35676449","host_type":"repository"},{"url":"https://doaj.org/article/cb415b47ad15403abc498a12c517ce80","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9177860","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9177860","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9177860?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1101/2022.02.06.479288","host_type":""},{"url":"https://www.biorxiv.org/content/biorxiv/early/2022/02/06/2022.02.06.479288.full.pdf","host_type":""},{"url":"https://dx.doi.org/10.5167/uzh-219097","host_type":""},{"url":"http://dx.doi.org/10.1038/s42003-022-03496-5","host_type":""},{"url":"https://doi.org/10.5167/uzh-219097","host_type":""},{"url":"https://www.zora.uzh.ch/id/eprint/219097/","host_type":""},{"url":"https://doi.org/https://doi.org/10.1038/s42003-022-03496-5","host_type":""}],"fields_of_study":["Prion Diseases and Protein Misfolding","Olfactory and Sensory Function Studies","CRISPR and Genetic Engineering","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":["Aging","Animals","Brain","Creutzfeldt-Jakob Syndrome","Prions","Prion Diseases","Mice"],"keywords":["Brain aging","Neuroscience","Aging brain","Senescence","Biology","Human brain","Downregulation and upregulation","Mammalian brain","Gene","Cell biology","Genetics","Cognition","570","Aging","QH301-705.5","Prions","10208 Institute of Neuropathology","610","Medicine (miscellaneous)","610 Medicine & health","Genetics and Molecular Biology","1100 General Agricultural and Biological Sciences","Article","Creutzfeldt-Jakob Syndrome","Prion Diseases","Mice","1300 General Biochemistry, Genetics and Molecular Biology","Animals","Biology (General)","610 Medicine &amp; health","Animal","Brain","2701 Medicine (miscellaneous)","Prion Disease","General Biochemistry","570 Life sciences; biology","General Agricultural and Biological Sciences"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"No poverty"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T12:13:33.919287Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}