{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ma L"],"funding":["Johns Hopkins University Older Americans Independence Center","NIA NIH HHS","National Institutes of Health","NIH HHS","National Institute on Aging","Beijing Natural Science Foundation"],"pagination":["211-215"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7812426"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["76(2)"],"pubmed_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, Biological sciences and medical sciences"],"pubmed_title":["Targeted Deletion of Interleukin-6 in a Mouse Model of Chronic Inflammation Demonstrates Opposing Roles in Aging: Benefit and Harm."],"pmcid":["PMC7812426"],"funding_grant_id":["7202059","P30 AG021334","R01 AG046441","R01-AG046441","P30-AG021334","S10 OD025226","T32AG058527","T32 AG058527"],"pubmed_authors":["Nidadavolu LS","Yang H","Abadir PM","Ling S","Ma L","Tan J","Nguyen T","Westbrook R","Hinson J","Moaddel R","Tsui BMW","Langdon J","Walston JD","Marx-Rattner R","Khadeer M","Lee TS","Wu Y","Le A"],"additional_accession":[]},"is_claimable":false,"name":"Targeted Deletion of Interleukin-6 in a Mouse Model of Chronic Inflammation Demonstrates Opposing Roles in Aging: Benefit and Harm.","description":"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.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Jan","modification":"2024-11-06T12:15:30.352Z","creation":"2022-02-10T15:51:46.128Z"},"accession":"S-EPMC7812426","cross_references":{"pubmed":["32585682"],"doi":["10.1093/gerona/glaa156"]}}