Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 63:391-398 (2008)
© 2008 The Gerontological Society of America

The Physical and Biological Characterization of a Frail Mouse Model

Jeremy Walston, Neal Fedarko, Huanle Yang, Sean Leng, Brock Beamer, Sara Espinoza, Anne Lipton, Howie Zheng and Kevin Becker

1 The Biology of Frailty Working Group, Johns Hopkins University, Division of Geriatric Medicine and Gerontology, Baltimore, Maryland.
2 National Institute on Aging, Baltimore, Maryland.

Address correspondence to Jeremy Walston, MD, John R. Burton Pavilion, 5505 Bayview Circle, Baltimore, MD 21224. E-mail: jwalston{at}jhmi.edu

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-10tm/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-10tm/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-10tm/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.

Key Words: Frailty • Mouse model






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