The physical and biological characterization of a frail mouse model
The physical and biological characterization of a frail mouse model
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DOI：
10.1093/gerona/63.4.391
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发表时间：
2008-04-01
影响因子：
5.1
通讯作者：
Becker, Kevin
中科院分区：
文献类型：
--
作者：
Walston, Jeremy;Fedarko, Neal;Becker, Kevin
背景资料。开发接近人类虚弱的动物模型对于促进病因学和以治疗为重点的虚弱研究是必要的。基因改变的IL-10(tm/tm)小鼠不表达抗炎细胞因子IL-10(IL-10)，并且像虚弱的人类一样，更容易被炎症途径激活。我们假设，随着年龄的增长，IL-10(tm/tm)小鼠将表现出与C57BL/6J对照小鼠类似的人类脆弱的物理和生物学特征。采用纵向物理特性设计和横断面生物特性设计，比较C57BL/6J背景下年龄匹配和性别匹配的IL-10(tm/tm)小鼠和对照小鼠的力量、活动、血清IL-6和骨骼肌基因表达。随着年龄的增长，IL-10(tm/tm)组的强度水平下降的速度明显快于对照组。与年轻的IL-10(tm/tm)小鼠相比，老年小鼠的血清IL-6水平显著升高，与年龄和性别匹配的C57BL/6J对照组小鼠相比，老年IL-10(tm/tm)小鼠的血清IL-6水平显著升高。125个基因在50周龄IL-10(tm/tm)和50周龄C57BL/6J小鼠骨骼肌中差异表达，其中许多基因与线粒体生物学和细胞凋亡有关。定量聚合酶链式反应检测到IL-10(tm/tm)年龄组之间的表达差异无统计学意义。这些物理和生物学发现表明，与C57BL/6J对照组小鼠相比，IL-10(tm/tm)小鼠在更早的年龄就出现了炎症和强度下降，这与人类的虚弱相一致。这一发现为进一步开发和利用IL-10(tm/tm)小鼠研究脆弱的生物学基础提供了理论依据。
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.