{"doi":"10.1093/gerona/glaa156","title":"Targeted Deletion of Interleukin-6 in a Mouse Model of Chronic Inflammation Demonstrates Opposing Roles in Aging: Benefit and Harm","abstract":"Chronic inflammation (CI) in older adults is associated with reduced health span and life span. Interleukin-6 (IL-6) is one CI marker that is strongly associated with adverse health outcomes and mortality in aging. We have previously characterized a mouse model of frailty and chronic inflammatory pathway activation (IL-10tm/tm, IL-10 KO) that demonstrates the upregulation of numerous proinflammatory cytokines, including IL-6. We sought to identify a more specific role for IL-6 within the context of CI and aging and developed a mouse with targeted deletion of both IL-10 and IL-6 (IL-10tm/tm/IL-6tm/tm, DKO). Phenotypic characteristics, cytokine measurements, cardiac myocardial oxygen consumption, physical function, and survival were measured in DKO mice and compared to age- and gender-matched IL-10 KO and wild-type mice. Our findings demonstrate that selective knockdown of IL-6 in a frail mouse with CI resulted in the reversal of some of the CI-associated changes. We observed increased protective mitochondrial-associated lipid metabolites, decreased cardiac oxaloacetic acid, improved myocardial oxidative metabolism, and better short-term functional performance in DKO mice. However, the DKO mice also demonstrated higher mortality. This work shows the pleiotropic effects of IL-6 on aging and frailty.","journal":"The Journals of Gerontology Series A","year":2020,"id":104035,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9582,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":264348,"name":"Lolita S. Nidadavolu","orcid":"0000-0003-2433-0728","position":1,"is_corresponding":false},{"id":291301,"name":"Huanle Yang","orcid":"0000-0003-0067-2176","position":2,"is_corresponding":false},{"id":507307,"name":"Jackie Langdon","orcid":null,"position":3,"is_corresponding":false},{"id":291297,"name":"Reyhan Westbrook","orcid":"0000-0001-9233-9295","position":4,"is_corresponding":false},{"id":506124,"name":"B.M.W. Tsui","orcid":"0000-0001-7928-5093","position":5,"is_corresponding":false},{"id":507308,"name":"Taek-Soo Lee","orcid":null,"position":6,"is_corresponding":false},{"id":507309,"name":"Jared Hinson","orcid":null,"position":7,"is_corresponding":false},{"id":506125,"name":"Shizhang Ling","orcid":"0000-0002-6856-3577","position":8,"is_corresponding":false},{"id":507310,"name":"Ruth Marx-Rattner","orcid":null,"position":9,"is_corresponding":false},{"id":507311,"name":"Yuqiong Wu","orcid":null,"position":10,"is_corresponding":false},{"id":506126,"name":"Tu Nguyen","orcid":"0000-0003-0014-4349","position":11,"is_corresponding":false},{"id":506127,"name":"Jessica Tan","orcid":"0000-0001-7917-4190","position":12,"is_corresponding":false},{"id":293403,"name":"Mohammed Khadeer","orcid":null,"position":13,"is_corresponding":false},{"id":291303,"name":"Ruin Moaddel","orcid":"0000-0002-6812-0127","position":14,"is_corresponding":false},{"id":232235,"name":"Anne Le","orcid":"0000-0002-2958-8149","position":15,"is_corresponding":false},{"id":57359,"name":"Jeremy Walston","orcid":"0000-0002-6965-2723","position":16,"is_corresponding":false},{"id":264351,"name":"Peter Abadir","orcid":"0000-0002-8186-0066","position":17,"is_corresponding":false},{"id":506123,"name":"Lina Ma","orcid":"0000-0001-7630-6960","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:43:22.755723Z","pmid":"32585682","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":[]}