Inflammation and mortality in a frail mouse model

Fred Ko, Qilu Yu, Qian Li Xue, Wenliang Yao, Cory Brayton, Huanle Yang, Neal Fedarko, Jeremy Walston

Research output: Contribution to journalArticle

Abstract

Mice homozygous for targeted deletion of the interleukin 10 gene (Il-10) have been partially characterized as a model for human frailty. These mice have increased serum interleukin (IL)-6 in midlife, skeletal muscle weakness, and an altered skeletal muscle gene expression profile compared to age and sex-matched C57BL/6 (B6) control mice. In order to further characterize for use as a frailty model, we evaluated the evolution of inflammatory pathway activation, endocrine change, and mortality in these mice. Serum was collected in groups of ageand sex-matched B6.129P2-Il10tm1Cgn/J (IL-10tm/tm) mice and B6 control mice at age 12, 24, 48, 72, and 90 weeks. Cytokines including IL-6, interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), chemokine (C-X-C motif) ligand 1 (KC), IL-12, and IL-10 were measured using electro-chemiluminescent multiplex immunoassay and insulin-like growth factor 1 (IGF-1) was measured using solid-phase enzyme-linked immunosorbent assay. A separate longitudinal cohort was monitored from age 35 weeks to approximately 100 weeks. Survival was evaluated by Kaplan-Meier survival estimates and detailed necropsy information was gathered in a subset of mice that died or were sacrificed. In IL-10tm/tm mice compared to B6 controls, serum IL-6, IL-1β, TNF-α, IFN-γ, KC levels were significantly elevated across the age groups, serum mean IGF-1 levels were higher in the 48-week-old groups, and overall mortality rate was significantly higher. The quadratic relationship between IGF-1 and age was significantly different between the two strains of mice. Serum IL-6 was positively associated with IGF-1 but the effect was significantly larger in IL-10tm/tm mice. These findings provide additional rationale for the use of the IL-10tm/tm mouse as a model for frailty and for low-grade inflammatory pathway activation.

Original languageEnglish (US)
Pages (from-to)705-715
Number of pages11
JournalAGE
Volume34
Issue number3
DOIs
StatePublished - Jun 1 2012

Keywords

  • C57BL/6
  • Frailty
  • IGF-1
  • IL-10
  • IL-6
  • Inflammation
  • Mortality

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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