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Development of a cyclophosphamide stress test to predict resilience to aging in mice.
GeroScience ( IF 5.3 ) Pub Date : 2020-07-01 , DOI: 10.1007/s11357-020-00222-z
Lida Zhu 1 , Yan Dou 1 , Marianne Bjorner 1 , Warren Ladiges 1
Affiliation  

The concept of resilience, defined as the ability to recover from stress, is a potential platform to predict healthy aging. However, specific stress tests for resilience have not yet been fully established in humans so investigations in animal models are of interest. The chemotherapeutic drug cyclophosphamide (Cyp) was selected as a chemical stressor to investigate resilience response in C57Bl/6 male mice at 4, 15, and 28 months of age. Following a single intraperitoneal injection of Cyp (100 mg/kg), tail blood was collected for counting white blood cells (WBC) every other day for 25 days, and physiological performance tests performed. Cyp induced a consistent pattern in neutrophil count in all three age groups, with a nadir at day 5 and a rebound at day 7 with different rates in each group. The neutrophil to lymphocyte ratio (NLR) showed an age-dependent rebound response 7 days after Cyp injection, with a similar pattern of decline back toward baseline. Mice in the 15-month age group with high pre-injection Cyp NLR had significantly higher total WBC counts after Cyp injection compared with mice with low pre-injection Cyp NLR, indicating a correlation between NLR and Cyp-altered WBC counts. In addition, mice with high pre-injection Cyp NLR showed significant learning impairment compared with mice with low pre-injection Cyp NLR, suggesting low NRL intensity can predict resilience to age-related cognitive decline. These observations provide the rationale to translate findings from the mouse to humans in developing in vitro Cyp stress tests.



中文翻译:

预测小鼠抗衰老能力的环磷酰胺压力测试的开发。

恢复力的概念被定义为从压力中恢复的能力,是预测健康衰老的潜在平台。然而,尚未在人类中完全建立针对弹性的特定压力测试,因此对动物模型的研究引起了人们的兴趣。选择化学治疗药物环磷酰胺(Cyp)作为化学应激源,以研究4、15和28个月大的C57Bl / 6雄性小鼠的弹性反应。一次腹膜内注射Cyp(100 mg / kg)后,每隔25天收集一次尾血用于白细胞(WBC)计数,并进行生理性能测试。Cyp诱导了所有三个年龄组中性粒细胞计数的一致模式,第5天达到最低点,第7天出现反弹,各组的比率不同。Cyp注射后7天,嗜中性白细胞与淋巴细胞之比(NLR)显示出年龄依赖性反弹反应,并有类似的下降趋势。与注射前Cyp NLR较低的小鼠相比,注射Cyp NLR较高的15个月龄小鼠的总WBC计数明显高于注射Cyp NLR较低的小鼠,这表明NLR与Cyp改变的WBC计数之间存在相关性。此外,与注射前低Cyp NLR的小鼠相比,注射前Cyp NLR较高的小鼠表现出明显的学习障碍,这表明低NRL强度可以预测对与年龄相关的认知下降的适应力。这些发现提供了在开展体外Cyp压力测试时将小鼠的发现转化为人类的依据。下降到基线的情况类似。与注射前Cyp NLR较低的小鼠相比,注射Cyp NLR较高的15个月龄小鼠的总WBC计数明显高于注射Cyp NLR较低的小鼠,这表明NLR与Cyp改变的WBC计数之间存在相关性。此外,与低注射前Cyp NLR相比,注射前Cyp NLR高的小鼠表现出明显的学习障碍,这表明低NRL强度可以预测与年龄相关的认知衰退的适应力。这些观察结果提供了在开展体外Cyp压力测试时将小鼠的发现转化为人类的依据。下降到基线的情况类似。与注射前Cyp NLR较低的小鼠相比,注射Cyp NLR较高的15个月龄小鼠的总WBC计数明显高于注射Cyp NLR较低的小鼠,这表明NLR与Cyp改变的WBC计数之间存在相关性。此外,与注射前低Cyp NLR的小鼠相比,注射前Cyp NLR较高的小鼠表现出明显的学习障碍,这表明低NRL强度可以预测对与年龄相关的认知下降的适应力。这些观察结果提供了在开展体外Cyp压力测试时将小鼠的发现转化为人类的依据。表示NLR和Cyp更改的WBC计数之间存在相关性。此外,与注射前低Cyp NLR的小鼠相比,注射前Cyp NLR较高的小鼠表现出明显的学习障碍,这表明低NRL强度可以预测对与年龄相关的认知下降的适应力。这些观察结果提供了在开展体外Cyp压力测试时将小鼠的发现转化为人类的依据。表示NLR和Cyp更改的WBC计数之间存在相关性。此外,与低注射前Cyp NLR相比,注射前Cyp NLR高的小鼠表现出明显的学习障碍,这表明低NRL强度可以预测与年龄相关的认知衰退的适应力。这些观察结果提供了在开展体外Cyp压力测试时将小鼠的发现转化为人类的依据。

更新日期:2020-07-24
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