{"doi":"10.1016/j.cmet.2023.10.014","title":"Stress-induced β cell early senescence confers protection against type 1 diabetes","abstract":"During the progression of type 1 diabetes (T1D), β cells are exposed to significant stress and, therefore, require adaptive responses to survive. The adaptive mechanisms that can preserve β cell function and survival in the face of autoimmunity remain unclear. Here, we show that the deletion of the unfolded protein response (UPR) genes Atf6α or Ire1α in β cells of non-obese diabetic (NOD) mice prior to insulitis generates a p21-driven early senescence phenotype and alters the β cell secretome that significantly enhances the leukemia inhibitory factor-mediated recruitment of M2 macrophages to islets. Consequently, M2 macrophages promote anti-inflammatory responses and immune surveillance that cause the resolution of islet inflammation, the removal of terminally senesced β cells, the reduction of β cell apoptosis, and protection against T1D. We further demonstrate that the p21-mediated early senescence signature is conserved in the residual β cells of T1D patients. Our findings reveal a previously unrecognized link between β cell UPR and senescence that, if leveraged, may represent a novel preventive strategy for T1D.","journal":"Cell Metabolism","year":2023,"id":319683,"datarank":0.6010999777848708,"base_score":4.007333185232471,"endowment":4.007333185232471,"self_citation_contribution":0.6010999777848708,"citation_network_contribution":0.0,"self_endowment_contribution":0.6010999777848708,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":54,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9583,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":396821,"name":"Gulcan Semra Sahin","orcid":"0000-0002-5855-8547","position":1,"is_corresponding":false},{"id":650328,"name":"Chien-Wen Chen","orcid":"0000-0002-1214-4058","position":2,"is_corresponding":false},{"id":256319,"name":"Shreyash Sonthalia","orcid":"0000-0003-1912-7901","position":3,"is_corresponding":false},{"id":1030078,"name":"Sandra Marín Cañas","orcid":null,"position":4,"is_corresponding":false},{"id":256318,"name":"Hülya Zeynep Oktay","orcid":"0000-0002-1333-2122","position":5,"is_corresponding":false},{"id":769564,"name":"Alexander T. Duckworth","orcid":"0000-0002-7713-4117","position":6,"is_corresponding":false},{"id":820615,"name":"Gabriel Brawerman","orcid":"0000-0002-4198-8444","position":7,"is_corresponding":false},{"id":7389,"name":"Peter J. Thompson","orcid":"0000-0002-6851-8899","position":8,"is_corresponding":false},{"id":428227,"name":"Maria Hatzoglou","orcid":"0000-0003-2037-1231","position":9,"is_corresponding":false},{"id":262820,"name":"Décio L. Eizirik","orcid":"0000-0003-2453-5889","position":10,"is_corresponding":false},{"id":7366,"name":"Feyza Engin","orcid":"0000-0002-7987-5381","position":11,"is_corresponding":false},{"id":257323,"name":"Hugo Lee","orcid":null,"position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:07:17.361058Z","pmid":"37949065","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":[]}