The physical and biological characterization of a frail mouse model

Abstract

Background. The development of animal models that approximate human frailty is necessary to facilitate etiologic and treatment-focused frailty research. The genetically altered IL-10tm/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-10tm/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-10tm/tm compared to control mice with increasing age. Serum IL-6 levels were significantly higher in older compared to younger IL-10tm/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-10tm/tm age groups were identified by quantitative polymerase chain reaction. Conclusion. These physical and biological findings suggest that the IL-10tm/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-10tm/tm mouse to study the biological basis of frailty.