A Murine Frailty Index Based on Clinical and Laboratory Measurements: Links Between Frailty and Pro-inflammatory Cytokines Differ in a Sex-Specific Manner
A Murine Frailty Index Based on Clinical and Laboratory Measurements: Links Between Frailty and Pro-inflammatory Cytokines Differ in a Sex-Specific Manner
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DOI：
10.1093/gerona/gly117
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发表时间：
2019-03-01
影响因子：
5.1
通讯作者：
Howlett, Susan E.
中科院分区：
文献类型：
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作者：
Kane, Alice E.;Keller, Kaitlyn M.;Howlett, Susan E.
基于临床缺陷累积（FI-Clinical）的虚弱指数（FI）量化衰老小鼠中的虚弱。我们的目的是开发一种基于实验室测试的小鼠FI工具（FI-Lab），并研究年龄和性别对FI-Lab评分，FI-Clinical评分和组合（FI-Combined）的影响，以及探索虚弱和炎症之间的联系。研究使用了年龄较大（17和23个月）的C57 BL/6小鼠（两种性别）。我们基于年轻成人（12个月）的参考值偏差开发了FI-Lab（血压，血液化学，超声心动图），其显示出与人类FI-Lab工具相似的特征。有趣的是，虽然女性的FI-临床评分较高，但FI-实验室评分则相反，FI-综合评分无性别差异。所有三种FI工具都揭示了促炎细胞因子水平与衰老小鼠的虚弱之间的正相关性，这在性别之间存在差异。促炎细胞因子白细胞介素（IL）-6，IL-9和干扰素水平升高与老年女性的FI评分较高相关，而IL-12 p40水平随着老年男性FI评分的增加而升高。因此，基于常见实验室测试的FI工具可以量化小鼠的虚弱;自然衰老小鼠中炎症和虚弱评分之间的正相关性在性别之间存在差异。
A frailty index (FI) based on clinical deficit accumulation (FI-Clinical) quantifies frailty in aging mice. We aimed to develop a laboratory test-based murine FI tool (FI-Lab) and to investigate the effects of age and sex on FI-Lab scores, FI-Clinical scores, and the combination (FI-Combined), as well as to explore links between frailty and inflammation. Studies used older (17 and 23 months) C57BL/6 mice of both sexes. We developed an FI-Lab (blood pressure, blood chemistry, echocardiography) based on deviation from reference values in younger adults (12 months), which showed similar characteristics to a human FI-Lab tool. Interestingly, while FI-Clinical scores were higher in females, the opposite was true for FI-Lab scores and there was no sex difference in FI-Combined scores. All three FI tools revealed a positive correlation between pro-inflammatory cytokine levels and frailty in aging mice that differed between the sexes. Elevated levels of the pro-inflammatory cytokines interleukin (IL)-6, IL-9, and interferon- were associated with higher FI scores in aging females, while levels of IL-12p40 rose as FI scores increased in older males. Thus, an FI tool based on common laboratory tests can quantify frailty in mice; the positive correlation between inflammation and frailty scores in naturally aging mice differs between the sexes.