Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2008 Apr;63(4):391-8.
doi: 10.1093/gerona/63.4.391.

The physical and biological characterization of a frail mouse model

Jeremy Walston  1 , Neal Fedarko, Huanle Yang, Sean Leng, Brock Beamer, Sara Espinoza, Anne Lipton, Howie Zheng, Kevin Becker
Affiliations
Comparative Study

The physical and biological characterization of a frail mouse model

Jeremy Walston et al. J Gerontol A Biol Sci Med Sci. 2008 Apr.

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-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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Photographs of 18-month old IL-10tm/tm mice (top) and C57BL/6J control strain (bottom) at age 18 months.
Figure 2
Figure 2
Longitudinal muscle-related and weight-related phenotypic differences between female IL-10tm/tm (n = 10, red) and C57BL/6J control (n = 10, blue) mice by age in months. Individual observations are plotted with predicted means from mixed effects model.
See this image and copyright information in PMC

References

    1. Fried LP, Tangen C, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol Med Sci. 2001;56A:M1–M11. - PubMed
    1. Brown M, Sinacore DR, Binder EF, Kohrt WM. Physical and performance measures for the identification of mild to moderate frailty. J Gerontol Med Sci. 2000;55:M350–M355. - PubMed
    1. Chin APM, Dekker JM, Feskens EJ, Schouten EG, Kromhout D. How to select a frail elderly population? A comparison of three working definitions. J Clin Epidemiol. 1999;52:1015–1021. - PubMed
    1. Walston J, McBurnie MA, Newman A, et al. Frailty and activation of the inflammation and coagulation systems with and without clinical morbidities: results from the Cardiovascular Health Study. Arch Intern Med. 2002;162:2333–2341. - PubMed
    1. Leng S, Chaves P, Koenig K, Walston J. Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study. J Am Geriatr Soc. 2002;50:1268–1271. - PubMed

Publication types

MeSH terms