Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
School of Health and Human Performance, Dalhousie University, Halifax, NS, Canada.
J Gerontol A Biol Sci Med Sci. 2019 Feb 15;74(3):275-282. doi: 10.1093/gerona/gly117.
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-γ 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.
一种基于临床缺陷积累的衰弱指数（FI-Clinical）可用于量化衰老小鼠的衰弱程度。我们旨在开发一种基于实验室检测的小鼠衰弱指数工具（FI-Lab），并研究年龄和性别对 FI-Lab 评分、FI-Clinical 评分以及两者组合（FI-Combined）的影响，同时探讨衰弱与炎症之间的关系。该研究使用了雄性和雌性的较老年（17 个月和 23 个月）C57BL/6 小鼠。我们基于年轻成年人（12 个月）的参考值偏差开发了一种 FI-Lab（血压、血液化学、超声心动图），其特征与人类 FI-Lab 工具相似。有趣的是，虽然 FI-Clinical 评分在雌性中较高，但 FI-Lab 评分则相反，且在 FI-Combined 评分中没有性别差异。所有三种 FI 工具都显示，在衰老小鼠中，促炎细胞因子水平与衰弱之间存在正相关，且这种相关性在性别之间存在差异。在衰老雌性小鼠中，促炎细胞因子白细胞介素（IL）-6、IL-9 和干扰素-γ水平升高与较高的 FI 评分相关，而在老年雄性小鼠中，随着 FI 评分的升高，IL-12p40 水平也随之升高。因此，基于常见实验室检测的 FI 工具可用于量化小鼠的衰弱程度；在自然衰老的小鼠中，炎症与衰弱评分之间的正相关性在性别之间存在差异。
