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 inflam...

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Veröffentlicht in:The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2021-02, Vol.76 (2), p.211-215
Hauptverfasser: Ma, Lina, Nidadavolu, Lolita S, Yang, Huanle, Langdon, Jackie, Westbrook, Reyhan, Tsui, Benjamin M W, Lee, Taek-Soo, Hinson, Jared, Ling, Shizhang, Marx-Rattner, Ruth, Wu, Yuqiong, Nguyen, Tu, Tan, Jessica, Khadeer, Mohammed, Moaddel, Ruin, Le, Anne, Walston, Jeremy D, Abadir, Peter M
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Sprache:eng
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Zusammenfassung: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.
ISSN:1079-5006
1758-535X
DOI:10.1093/gerona/glaa156