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Effects of long-term in vivo micro-CT imaging on hallmarks of osteopenia and frailty in aging mice.
PLOS ONE ( IF 2.9 ) Pub Date : 2020-09-23 , DOI: 10.1371/journal.pone.0239534
Ariane C Scheuren 1 , Gisela A Kuhn 1 , Ralph Müller 1
Affiliation  

In vivo micro-CT has already been used to monitor microstructural changes of bone in mice of different ages and in models of age-related diseases such as osteoporosis. However, as aging is accompanied by frailty and subsequent increased sensitivity to external stimuli such as handling and anesthesia, the extent to which longitudinal imaging can be applied in aging studies remains unclear. Consequently, the potential of monitoring individual mice during the entire aging process–from healthy to frail status–has not yet been exploited. In this study, we assessed the effects of long-term in vivo micro-CT imaging—consisting of 11 imaging sessions over 20 weeks—on hallmarks of aging both on a local (i.e., static and dynamic bone morphometry) and systemic (i.e., frailty index (FI) and body weight) level at various stages of the aging process. Furthermore, using a premature aging model (PolgA(D257A/D257A)), we assessed whether these effects differ between genotypes. The 6th caudal vertebrae of 4 groups of mice (PolgA(D257A/D257A) and PolgA(+/+)) were monitored by in vivo micro-CT every 2 weeks. One group was subjected to 11 scans between weeks 20 and 40 of age, whereas the other groups were subjected to 5 scans between weeks 26–34, 32–40 and 40–46, respectively. The long-term monitoring approach showed small but significant changes in the static bone morphometric parameters compared to the other groups. However, no interaction effect between groups and genotype was found, suggesting that PolgA mutation does not render bone more or less susceptible to long-term micro-CT imaging. The differences between groups observed in the static morphometric parameters were less pronounced in the dynamic morphometric parameters. Moreover, the body weight and FI were not affected by more frequent imaging sessions. Finally, we observed that longitudinal designs including baseline measurements at young adult age are more powerful at detecting effects of in vivo micro-CT imaging on hallmarks of aging than cross-sectional comparisons between multiple groups of aged mice subjected to fewer imaging sessions.



中文翻译:


长期体内显微 CT 成像对衰老小鼠骨质减少和虚弱特征的影响。



体内显微CT已被用于监测不同年龄小鼠的骨微结构变化以及骨质疏松症等与年龄相关的疾病模型。然而,由于衰老伴随着虚弱以及随后对处理和麻醉等外部刺激的敏感性增加,纵向成像在衰老研究中的应用程度仍不清楚。因此,在整个衰老过程(从健康到虚弱状态)中监测个体小鼠的潜力尚未得到开发。在这项研究中,我们评估了长期体内显微 CT 成像(包括 20 周内的 11 次成像)对局部(即静态和动态骨形态测量)和全身(即,衰老过程各个阶段的衰弱指数(FI)和体重)水平。此外,使用过早衰老模型(PolgA (D257A/D257A) ),我们评估了这些影响在基因型之间是否存在差异。每2周对4组小鼠(PolgA (D257A/D257A)和PolgA (+/+) )的6尾椎进行体内显微CT监测。一组在 20 周至 40 周之间进行了 11 次扫描,而其他组分别在 26-34 周、32-40 周和 40-46 周之间进行了 5 次扫描。长期监测方法显示,与其他组相比,静态骨形态测量参数发生了微小但显着的变化。然而,没有发现群体和基因型之间的相互作用,这表明 PolgA 突变不会使骨骼或多或少对长期显微 CT 成像敏感。 在静态形态测量参数中观察到的组间差异在动态形态测量参数中不太明显。此外,体重和 FI 不受更频繁的成像检查的影响。最后,我们观察到,与多组接受较少成像的老年小鼠之间的横断面比较相比,包括年轻成年时基线测量在内的纵向设计在检测体内显微 CT 成像对衰老标志的影响方面更有效。

更新日期:2020-09-23
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