Journal
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
Volume 76, Issue 2, Pages 211-215Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glaa156
Keywords
Interleukin-6; Interleukin-10; Knockout; Lysophosphatidylcholine; Mitochondria
Categories
Funding
- National Institute on Aging at the National Institutes of Health [R01-AG046441]
- Johns Hopkins University Older Americans Independence Center (National Institute on Aging) [P30-AG021334]
- Beijing Natural Science Foundation [7202059]
- Translational Aging Research Training Program, National Institute on Aging [T32AG058527]
- Intramural Research Program of the National Institute on Aging at the National Institutes of Health
- Shared Instrument Grant-S10 - National Institutes of Health [1S10OD025226-01]
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Selective knockdown of IL-6 in a frail mouse with chronic inflammation can reverse some changes associated with chronic inflammation, but it also leads to higher mortality.
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-10(tm/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-10(tm/tm)/IL-6(tm/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 wildtype 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.
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