The physical and biological characterization of a frail mouse model.
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.


CONCLUSIONS
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.
Walston
Jeremy
J
The Biology of Frailty Working Group, Johns Hopkins University, Baltimore, MD 21224, USA. jwalston@jhmi.edu
Fedarko
Neal
N
Yang
Huanle
H
Leng
Sean
S
Beamer
Brock
B
Espinoza
Sara
S
Lipton
Anne
A
Zheng
Howie
H
Becker
Kevin
K
D000367:Age Factors; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D000818:Animals; D003430:Cross-Sectional Studies; D005260:Female; D016330:Frail Elderly; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D009043:Motor Activity; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000502:physiology*
D015850:Interleukin-6; D016753:Interleukin-10