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.
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.
Authors: T S Tanaka; S A Jaradat; M K Lim; G J Kargul; X Wang; M J Grahovac; S Pantano; Y Sano; Y Piao; R Nagaraja; H Doi; W H Wood; K G Becker; M S Ko Journal: Proc Natl Acad Sci U S A Date: 2000-08-01 Impact factor: 11.205
Authors: Jeremy Walston; Evan C Hadley; Luigi Ferrucci; Jack M Guralnik; Anne B Newman; Stephanie A Studenski; William B Ershler; Tamara Harris; Linda P Fried Journal: J Am Geriatr Soc Date: 2006-06 Impact factor: 5.562
Authors: Mariana Santiago-Lomelí; Luis E Gómez-Quiroz; Víctor M Ortíz-Ortega; David Kershenobich; Maria Concepción Gutiérrez-Ruiz Journal: Life Sci Date: 2005-04-15 Impact factor: 5.037
Authors: L P Fried; C M Tangen; J Walston; A B Newman; C Hirsch; J Gottdiener; T Seeman; R Tracy; W J Kop; G Burke; M A McBurnie Journal: J Gerontol A Biol Sci Med Sci Date: 2001-03 Impact factor: 6.053
Authors: Sean X Leng; Anne R Cappola; Ross E Andersen; Marc R Blackman; Kathleen Koenig; Michael Blair; Jeremy D Walston Journal: Aging Clin Exp Res Date: 2004-04 Impact factor: 3.636