First Author | Walston J | Year | 2008 |
Journal | J Gerontol A Biol Sci Med Sci | Volume | 63 |
Issue | 4 | Pages | 391-8 |
PubMed ID | 18426963 | Mgi Jnum | J:319869 |
Mgi Id | MGI:6865803 | Doi | 10.1093/gerona/63.4.391 |
Citation | Walston J, et al. (2008) The physical and biological characterization of a frail mouse model. J Gerontol A Biol Sci Med Sci 63(4):391-8 |
abstractText | BACKGROUND: The development of animal models that approximate human frailty is necessary to facilitate etiologic and treatment-focused frailty research. The genetically altered IL-10(tm/tm) mouse does not express the antiinflammatory cytokine interleukin 10 (IL-10) and is, like frail humans, more susceptible to inflammatory pathway activation. We hypothesized that with increasing age, IL-10(tm/tm) mice would develop physical and biological characteristics similar to those of human frailty as compared to C57BL/6J control mice. METHODS: Strength, activity, serum IL-6, and skeletal muscle gene expression were compared between age-matched and gender-matched IL-10(tm/tm) mice on C57BL/6J background and C57BL/6J control mice using a longitudinal design for physical characteristics and cross-sectional design for biological characteristics. RESULTS: Strength levels declined significantly faster in IL-10(tm/tm) compared to control mice with increasing age. Serum IL-6 levels were significantly higher in older compared to younger IL-10(tm/tm) mice and were significantly higher in older IL-10(tm/tm) compared to age- and gender-matched C57BL/6J control mice. One hundred twenty-five genes, many related to mitochondrial biology and apoptosis, were differentially expressed in skeletal muscle between 50-week-old IL-10(tm/tm) and 50-week-old C57BL/6J mice. No expression differences between IL-10(tm/tm) age groups were identified by quantitative polymerase chain reaction. CONCLUSION: These physical and biological findings suggest that the IL-10(tm/tm) mouse develops inflammation and strength decline consistent with human frailty at an earlier age compared to C57BL/6J control type mice. This finding provides rationale for the further development and utilization of the IL-10(tm/tm) mouse to study the biological basis of frailty. |